Doctoral Researchers

 
Allert, Stefanie

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JSMC Fellow

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Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Dept. Microbial Pathogenicity Mechanisms
PhD Project:

Pathogenicity mechanisms of Candida albicans during translocation through epithelial barriers

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Abstract: Candida albicans normally exists as a harmless commensal on mucosal surfaces, especially in the gut of healthy humans. As one of the most important opportunistic fungal pathogens of...
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... humans, C. albicans can become pathogenic under certain predisposing conditions, leading to severe superficial or even life-threatening systemic infections. The aim of this project is to characterize the transition of C. albicans from colonisation to translocation from the gut - as the main reservoir – to the bloodstream, from where the fungus can infect almost all organs and can cause systemic disease. Thereby fungal factors and attributes that are characteristic or essential for translocation through intestinal epithelial tissue are predicted to be important pathogenicity factors. To elucidate translocation-relevant genes, large-scale mutant libraries will be screened for reduced ability to cause damage of intestinal cells. On the other hand, genome-wide transcription profiles of C. albicans during translocation will be obtained using microarray technologies. Detailed analysis of identified genes, which are expressed during translocation, with an emphasis on genes of unknown function, will be performed and corresponding mutant strains generated. The influence of transient physiological alterations in the gut for triggering C. albicans translocation will be investigated by establishing in vitro gut-mimicking conditions. For example, parameters such as pH or O2 concentration will be manipulated. The results are expected to elucidate molecular and cellular pathogenicity mechanisms enabling and regulating intestinal tissue invasion and dissemination of the fungal pathogen C. albicans during the initial phase of systemic infections. The identified factors, essential for translocation through the gut, represent potential drug targets or biomarkers for clinical application.
 
 
Altwasser, Robert

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JSMC Fellow

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Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Research Group: Systems Biology / Bioinformatics
PhD Project:

Transcriptome data analysis and modeling of Aspergillus fumigatus – phagocytes interaction

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Abstract: Dynamic models for the interaction between fungal pathogen A. fumigatus and phagocytes shall be inferred from RNA-Seq- and microarray-based gene expression data integrating the...
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... available prior knowledge [1]. RNA-seq data analysis will allow to search for splice variants and small regulatory non-coding RNA species and to study their impact for the fungal phagocytose interaction. The inferred models will be aggregated and reduced to minimal models and delivered to the Research Group for Applied Systems Biology of the HKI (Prof. Thilo Figge) where the models will be integrated into agent-based simulation of spatiotemporal events during host-pathogen interaction.
 
 
Amin, Shayista

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ILRS Student

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Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Dept. Cell and Molecular Biology
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Junior Research Group
Chemistry of Microbial Communication
PhD Project:

Host Pathogen interactions, Aspergillus fumigatus and PET-CT Technology

 
 
Arras, Matthias

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Institute/Dep.
Friedrich Schiller University Jena
Institute for Materials Science and Technology (IMT)
PhD Project:

Nanostructred Polymers

 
 
Barnett, Robert

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ILRS Student

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Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Junior Research Group
Chemistry of Microbial Communication
PhD Project:

Discovery of Small Molecule Inhibitors of Multicellular Development

 
 
Baumert, Julia

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GRK1257 Student

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Institute/Dep.
Max Planck Institute for Biogeochemistry
Dept. Biogeochemical Processes
PhD Project:

Microbial mechanisms of the weathering, transformation and decomposition of organic compounds at the organic-mineral interface

 
 
Bechmann, Marcel

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JSMC Fellow

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Institute/Dep.
Helmholtz Centre for Environmental Research - UFZ
Department of Computational
Environmental Systems
Friedrich Schiller University Jena
Institute of Geosciences
Chair for Hydrogeology
PhD Project:

Integrated model of water and nutrient uptake by roots in the rhizosphere

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Abstract: Background: Soil-plant-microorganisms interactions make the rhizosphere a unique environment with dynamic properties far different from those of the bulk soil8. This has a profound...
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... consequence on rhizosphere processes such as microbial activities, water distribution, and nutrient and water uptake by plant roots. However, common models of water and nutrient uptake by roots are based on brute-force averaging approaches which assume that the rhizosphere has the same properties as the bulk soil. Our own research: In recent studies we observed that water distribution in the rhizosphere is influenced by rhizosphere properties during drying and rewetting periods3. We explained this by presence of mucilage exuded by roots and micro-organisms in the rhizosphere (Figure). Mucilage is composed mostly of polysaccharides and it has a very high water holding capacity5,7. It acts as a buffer to protect micro-organisms and roots from desiccation and osmotic stress1,4. We expect that mucilage improves the unsaturated hydraulic connectivity between soil and roots, thereby helping plants to face drought conditions. Our own research: In recent studies we observed that water distribution in the rhizosphere is influenced by rhizosphere properties during drying and rewetting periods3. We explained this by presence of mucilage exuded by roots and micro-organisms in the rhizosphere (Figure). Mucilage is composed mostly of polysaccharides and it has a very high water holding capacity5,7. It acts as a buffer to protect micro-organisms and roots from desiccation and osmotic stress1,4. We expect that mucilage improves the unsaturated hydraulic connectivity between soil and roots, thereby helping plants to face drought conditions. Project aim: Objective of the proposed study is to model water and nutrient uptake by roots including the specific properties of the rhizosphere. The hydraulic properties of the rhizosphere have been estimated by previous experiments with neutron radiography3. These properties could be implemented in existing models of root water uptake6. The second step would be to describe the dynamics of the rhizosphere in response to interactions of plants with fungi and bacterial microorganisms. Such interactions will modify the hydraulic properties of the rhizosphere and the water uptake with dynamics that cannot be explained only by hydraulic forces. The third step would consist in implementing a model for nutrient uptake. Methodology: Existing water uptake models could be implemented by considering the rhizosphere as a region with distinct properties. This could be done analytically by extending the approach described in 2 to two domains, or numerically by solving the Richards equation in two sub-domains. The interactions between micro-organisms, including fungi and bacteria, with the plant rhizosphere could be modelled by considering the rhizosphere a medium with hydraulic properties that change in time in response to microbial activity – as an effect of plant/microbe exudates and EPS. The involvement of fungi with their exudates, glucans, or uptake of nutrients will be implemented as well. Using pore network models could be an option for describing the varying connectivity of sites at changing water saturation and their effects on microbial mobility and physiology. Perspective: The proposed research will provide a holistic approach to describe interactions between rhizosphere transport properties and plant and microbial communities at the pore scale. References: 1Chenu C. 1993. Geoderma, 56: 143-156. 2De Villigen P. et al. 1987, PhD diss. Wageningen Agric. Univ. 3Carminati A. et al. (in preparation) 4Or D. et al. 2007. Advances in Water Resources, 30: 1505-1527. 5Read DB et al. 1997. New Phytologist, 137:623-628. 6Schneider C. Doctoral student at UFZ (in preparation). 7Young IM. 1995. New Phytologist, 130:135-139. 8Young IM and Crawford JW. 2004. Science, 304: 1634-1637.
 
 
Beder, Thomas

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JSMC Fellow

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Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Dept. Cell and Molecular Biology
PhD Project:

Pathogen/host communication: dual RNA expression dynamics to investigate differential patterns of virulence

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Abstract: Chlamydiaceae are a family of obligate intracellular pathogens that cause a wide range of human and animal diseases and face unique evolutionary constraints not encountered by...
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... free-living prokaryotes. Despite being a group of genetically homogeneous species, the members of this family show strong ecological heterogeneity and a diverse array of virulence phenotypes. Thus, Chlamydia abortus, a species that primarily infects ruminants, shares 98% of its genes with its closest relative, the host-generalist C. psittaci (Voigt et al, 2012). Yet they differ substantially in levels of invasiveness and rates of propagation, likely due to differences in the differential expression of bacterial factors related to virulence (Braukman et al., 2012). Infections, however, lead to a dynamic alteration of gene expression patterns in both the host cell and the invading parasite. These complex communication patterns between host and parasite determine whether a pathogen persists or is cleared from a host organism. A deep understanding of the infection process that may lead to the identification of new virulence factors in the pathogen, or novel pathways in a host cell responding to specific pathogenic agents, will require simultaneously monitoring global changes in expression of genes from both, host and pathogen at different time-points of infection. The progress in deep sequencing technology has only recently begun to make such a dual transcriptome sequencing approach feasible, and both, the bioinformatical and practical challenges remain substantial (Westerman et al. 2012). In this project we aim to comparatively investigate transcriptomic correlates of infection and virulence in the highly infectious Chlamydia psittaci and the moderately infectious C. abortus for a common mammalian host-cell at early, middle and late stages of infection. To this end, RNA-Seq (massively parallel sequencing of cDNA) will be performed on total RNA extracts from chlamydia-infected human epithelial pulmonal A549 cells. The data generated will be used to define the transcriptomes of the two chlamydial species in direct interaction with host cells as well as the global cellular response to infection of the host when challenged by differentially infectious parasites. This will achieve a comprehensive picture of the transcriptome-wide temporal dynamics of RNA expression during Chlamydia/host-cell interactions and, due to the close temporal congruence in determining host and pathogen transcriptomes, allow to establish tentative causal relationships between the expression of bacterial virulence factors and host defense by elucidating the interspecies interaction networks defining the microbial infection process (Tierney et al. 2012).
 
 
Beretta, Martina

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JSMC Fellow

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Institute/Dep.
University Hospital Jena
Clinic of Anaesthesiology and Intensive Care Medicine
Research Unit Experimental Anesthesiology
PhD Project:

Cell type-specific role of PI3Kgamma in sepsis-associated liver failure

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Abstract: The liver plays a pivotal role in the host response to life-threatening infections. We have shown that down regulation of expression and/or insertion of hepatocellular transport...
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... proteins (Mrp-2, Bsep) is a prognosis-limiting event that underlies cholestasis and depends on PI3Kgamma as KO mice are protected against excretory failure [1]. However, PI3Kgamma plays a crucial role in the migration of neutrophils and macrophages from the bloodstream to sites of infection, a hallmark of the host response [2]. As a consequence, unselective inhibition of this signaling event prevents hepatic dysfunction but is hampered by a concomitant severe immune defect. The aim of this project is to unravel the role of PI3Kgamma in liver (hepatocytes) as opposed to immune competent cells to develop strategies to prevent the sepsis induced hepatocytic defects in excretion and canalicular membrane organization without a concomitant immune defect. To this end we plan to use different approaches to specifically test the cell-type specific roles of PI3Kgamma in parenchymal and immune competent cells mediating sepsis induced hepatic excretory failure and systemic sepsis-related effects on the immune system. In addition, the project is aimed at better understanding the cell type specific signaling functions of PI3Kgamma and its downstream effectors in sepsis. This goal will be attained by characterizing different PI3Kgamma molecular partners, like GRK2, p87 and p101, as well as by defining the role of PI3Kgamma downstream effectors, with negative function like ArhGAP15 [3]. Finally, as PI3Kgamma plays both a kinase dependent and independent role in signal transduction events [4], a goal of this project is to assess the role of these two different PI3Kgamma activities in sepsis, both in neutrophils and in hepatocytes. On the long run this strategy will elucidate the potential of drugs that selectively target PI3Kgamma in individual cell types, such as hepatocytes. Work packages Year 1: Establishment of mouse models - PI3Kgamma KO, PI3Kgamma KD (transgenic mice expressing lipid kinase negative PI3Kgamma [4]), ArhGAP15 KO [3] - Cre/lox system for tissue specific expression of PI3Kgamma - Polymicrobial sepsis (PCI) and Candida sepsis. Characterization of phenotypes regarding hepatic excretory failure and immune functions of leukocytes. Year 2 and year 3: Investigation of sepsis induced signaling patterns of PI3Kgamma Hypothesized differential signaling reactions of PI3Kgamma and interaction partners (GRK2, p87 and p101, ArhGAP15) in sepsis induced organ failure will be analyzed in hepatocytes and leukocytes (neutrophils). Study of the role of PI3Kgamma kinase-independent roles in sepsis. Year 3: Pharmacological treatment of PI3Kgamma Effects of PI3Kgamma inhibitors on polymicrobial sepsis (PCI) and Candida sepsis. Comparative characterization of hepatic excretion and immune functions of leukocytes. References [1] P. Recknagel, F. A. Gonnert, M. Westermann, S. Lambeck, A. Lupp, A. Rudiger, A. Dyson, J. E. Carré, A. Kortgen, C. Krafft, J. Popp, C. Sponholz, I. Hilger, R. A. Claus, N. C. Riedemann, R. Wetzker, M. Singer, M. Trauner, M. Bauer (2012) Liver dysfunction with impaired phase I, II and III metabolism reflects an early and poor prognostic event in sepsis that depends on PI3K signalling. PLoS Med 9 e1001338. [2] E. Hirsch, V.L. Katanaev, C. Garlanda, O. Azzolino, L. Pirola, L. Silengo, S. Sozzani, A. Mantovani, F. Altruda, M. P. Wymann (2000) Central role for G protein-coupled phosphoinositide 3-kinase gamma in inflammation. Science 287, 1049–1053. [3] C. Costa, G. Germena, E.L. Martin-Conte, I. Molineris, E. Bosco, S. Marengo, O. Azzolino, F. Altruda, V.M. Ranieri, E. Hirsch E (2011) The RacGAP ArhGAP15 is a master negative regulator of neutrophil functions. Blood 118, 1099-108. [4] E. Patrucco, A. Notte, L. Barberis, G. Selvetella, A. Maffei, M. Brancaccio, S. Marengo, G. Russo, O. Azzolino, S. Rybalkin, L. Silengo, F. Altruda, R. Wetzker, M. Wymann, G. Lembo, E. Hirsch (2004) PI3Kgamma modulates the cardiac response to chronic pressure overload by distinct kinase-dependent and independent effects. Cell 118, 375-387.
 
 
Institute/Dep.
Friedrich Schiller University Jena
Institute of Microbiology
Microbial Communication
PhD Project:

Comparison of bacterial communities in groundwater aquifers of the Thuringian Basin with respect to their present stratigraphy

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Abstract: The INFLUINS (Integrated fluid dynamics in sedimentary basins) project investigates coupled dynamics of near surface and deep flow patterns of fluids, transported materials and...
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... component substances in the Thuringian Basin. The extensive basin landscape is located in eastern Germany and belongs to the Triassic period of Buntsandstein, Muschelkalk and Keuper, which crop out at the surface. Older sediments and Permian (Zechstein) can be found at the edges of the basin. With microbial investigations, we are analyzing the bacterial diversity of groundwater at different locations to see whether there are special patterns in bacterial distributions originating from the different rock strata. Furthermore, we are interested in the bacterial diversity of drilling cores and salt formations from the same locations. This will facilitate understanding fluid movement in the Thuringian Basin. We determined bacterial community from water samples out of nine natural springs and sixteen groundwater wells by cultivation and subsequent morphological, physiological and molecular identification. Results show that the largest proportions were found to be members of Bacilli and Gammaproteobacteria, including the genera Pseudomonas, Marinomonas, Bacillus, Marinobacter and Pseudoalteromonas. Statistical analysis have shown a higher overlap between sandstone- and limestone-derived communities as if compared to the salt formations. Next steps will be a comparison of cultivation-dependent and cultivation-independent methods to gain further information on bacterial strains which where uncultivable or suppressed by other bacteria strains.
 
 
Biermann, Michael

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JSMC Fellow

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Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Bio Pilot Plant
PhD Project:

Influence of the amino acid metabolism and stress responses during the induction phase of Escherichia coli for the production of recombinant proteins – measuring the signal exchange during high cell density fermentation

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Abstract: During High Cell Density Fermentation (HCDF) of Escherichia coli for the production of recombinant proteins it is known that misincooperation of rare amino acids can occur during...
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... protein expression. Some procedures to avoid the misincooperation were developed in the past but are not free-to-operate; also these methods are not fully understood on the molecular level. For therapeutically relevant proteins the ratio of misincooperation should be as low as possible, as all undesired protein byproducts need special attention during clinical studies and require intensive analytical characterization to obtain a biologics license application. During the Ph.D. thesis the applicant shall study possibilities to regulate and control the misincooperation ratio on molecular level and with bioprocessing tools. Special focus shall be paid to different induction regimens during the exponential growth phase of Escherichia coli. The influence of the intra –and extracellular amino acid metabolism during the HCDF shall be explored and if possible simulated. Finally intracellular stress responses during the induction period and signal exchange between the cells during high cell density fermentation can be analysed.
 
 
Bohnert, Markus

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JSMC Fellow

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Institute/Dep.
Friedrich Schiller University Jena
Institute of Pharmacy
Dep. of Pharmaceutical / Medicinal Chemistry
PhD Project:

Chemical ecology of the Honey Mushroom Armillaria mellea: Investigations on the mode of action of melleolide antibiotics

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Abstract: The melleolides are a family of sesquiterpene-orsellinate ester natural products exclusively produced by members of the homobasidiomycete genus Armillaria (honey mushroom). Many species...
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... within this widely distributed fungal genus are known as notorious butt and root rot agents. The host range of Armillaria is extraordinarily broad and includes hardwood and conifers, as well as fruit and ornamental trees. Although being an aggressive tree pathogen, Armillaria also serves a great positive role as ecological catalyst to depolymerize biomass and, therefore, maintain the carbon flux in forest habitats worldwide. Some filamentous fungi with which Armillaria is likely to interact in its natural habitat are transiently or permanently inhibited by the melleolides, while other fungi are completely resistant against them. This is suggestive of a role for chemical ecology and, more specifically, that Armillaria might have evolved these unique compounds as a means for selective negative interspecies communication. The molecular mechanisms of how the melleolides exert their inhibitory activity, as well as the exact basis of resistance against them, are unknown. Yet, this knowledge is critical to understand the principles of Armillaria chemical communication and to clarify which mechanism(s) some fungi utilize to disrupt the communicative processes by intrinsic resistance. To study the melleolides both from a chemical-ecological and from a pharmaceutical perspective, this JSMC-project will rely on biochemical and chemical approaches, as well as on fungal molecular biology.
 
 
Bondoc, Karen Grace

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JSMC Fellow

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Institute/Dep.
Friedrich Schiller University Jena
Institute for Inorganic and Analytical Chemistry
PhD Project:

Complex interactions during biofilm formation by benthic diatoms

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Abstract: Benthic diatoms are key players in the aquatic environment as they form biofilms which are important in ecosystem functioning. In this project, we will explore the signaling...
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... interactions that mediate the formation of these micro-scale communities. This project will focus on three independent topics on chemical gradients affecting surface processes. Nitzschia cf pellucida produces the allelopathic compound BrCN in the presence of competitors which shapes the patchy distribution of biofilm communities. Within this topic, we will use digital holographic microscopy (DHM) to determine release kinetics of this compound with respect to the presence of competitors and cell density. Moreover, feeding assays with isotope-labeled precursors will also help in elucidating the biosynthetic pathway for BrCN production. A model organism for diatom studies, Seminavis robusta will be used for the other two topics that will focus on chemical signals and nutrients that mediate the growth and settlement of this species to surfaces. First experiments showed chemoattraction of this organism to alox beads containing silicic acid. We will explore this mechanism by manipulating release of Si(OH)4 beads on the organism and determining its motility patterns. The last topic will make use of mass spectrometric imaging techniques to observe pheromone release in S. robusta. Mating types of this species (termed äs MT+ and MT-) release chemical cues that activate sexual behavior. Having an understanding how these signals are released in response to both mating types will give a more comprehensive view on this organism's cell cycle.
 
 
Brandes, Susanne

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ILRS Student

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Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Research Group Applied Systems Biology
PhD Project:

Analysis of Dynamic Properties in Biological Systems from Image Data

 
 
Brangsch, Hanka

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JSMC Fellow

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Institute/Dep.
Friedrich Schiller University Jena
Institute of Microbiology
Microbial Communication
PhD Project:

Control of heavy metal resistance genes in Streptomyces

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Abstract: Streptomycetes - soil living bacteria forming aerial mycelium with spores - are known for the production of secondary metabolites like antibiotics and siderophores. In our research...
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... group streptomycetes are used to determine the mechanisms of heavy metal resistance. The basis of this research is a streptomycete strain collection and the isolation of new strains from different heavy metal contaminated areas like the former uranium mining site Wismut in Eastern Thuringia, Germany. For the study of streptomycetes, an effective transformation system needs to be developed, which will allow the functional analyses of genes involved in heavy metal resistance within isolates from a test field site operated by the university since 2004 in the former uranium mining site in Eastern Thuringia. Candidate genes have been identified which await detailed analysis in vivo. Thus, the genetic system will be established with a strain isolated from this harsh environment.
 
 
Institute/Dep.
Max Planck Institute for Chemical Ecology
Dept. of Bioorganic Chemistry
PhD Project:

Molecular analysis of digestive fluids in pitcher plants

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Abstract: Species of the genus Nepenthes are carnivorous plants with specific organs, so called pitchers, to catch and digest animal prey. The lower part of the pitcher, the digestion zone...
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... (Figure 1), is covered inside with many multicellular, bifunctional glands, which not only secrete the digestion fluid but also take up released nutrients. In addition, these glands do the secretion of hydrolytic enzymes into the pitcher fluid used to digest prey and to protect against microbes. 1. In recent years some of these enzymes have been purified. Many of them belong to pathogenesis-related proteins (PR-proteins). Among others, the PR-1 protein was discovered in the Nepenthes pitcher fluid. The aim here, is the functional analysis of the heterologously expressed PR1-protein from Nepenthes-plants and to clearify its function during carnivory. Accordingly to this issue comes the question, if and how the pitcher fluid affects bacterial and fungal growth. Therefore, sterility of closed and open pitchers play a decisive role. 2. Beside this, proteases, in particular aspartic proteases, have been described in Nepenthes digestion fluid. For an easy detection of protease activities in Nepenthes, a novel, fluorescence resonance energy transfer (FRET)-based technique using an artificial substrate [1] was chosen as a method. Here, quenching is the basis for FRET assays. Together with the pitcher fluid that contains aspartic proteases, the substrate (Fluorophor-AA-AA-Quencher) is cleaved by these enzymes and as result, the released fluorescence can be measured. Thus, with this fluorescent substrate a fast and easy-to-handle tool for the investigation of proteases in Nepenthes is available, without further need of enzyme isolation.
 
 
Chen, Qian

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ILRS Student

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Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Junior Research Group
Chemistry of Microbial Communication
PhD Project:

The Role of Complement in Autoimmune Disease

 
 
Dewald, Carolin

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JSMC Fellow

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Institute/Dep.
Friedrich Schiller University Jena
Institute for Materials Science and Technology (IMT)
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Bio Pilot Plant
PhD Project:

Control of microbial adhesion through physically and chemically nanostructured materials surfaces for the reduction of materials-associated infections

 
 
Dix, Andreas

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Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Research Group: Systems Biology / Bioinformatics
PhD Project:

Predictive modelling of host-fungal pathogen interactions by reconstruction of gene regulatory networks

 
 
Dolke, Franziska

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JSMC Fellow

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Institute/Dep.
Max Planck Institute for Chemical Ecology
Dept. of Bioorganic Chemistry
PhD Project:

Small molecule signals in nematode-bacteria interactions

 
 
Institute/Dep.
Max Planck Institute for Chemical Ecology
Dept. of Bioorganic Chemistry
PhD Project:

Localization of elicitors and defensive compounds on plant leaf surfaces after infection or herbivory

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Abstract: The plant cuticle as an extra cellular interface covers the entire epidermal surface of all higher plants and regulates the water household and diffusion properties of the plant....
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... Moreover, the cuticula is the first barrier against herbivores, pathogens and aerial pollutants. The cuticle is mainly composed by a polymeric membrane (cutin) and long chain, aliphatic and highly nonpolar substances (waxes). The latter are classified into intracuticular waxes embedded in the cutin matrix, and epicuticular waxes deposited on the outer surface. Upon microbial infection or herbivory an intensive exchange of chemical signals occurs at the (surface) site of attack between the invading organism and the plant host. Although many of the involved molecules have been identified in the past, their local distribution around the infection site and the time course of their production remained largely unknown due to lacking analytical techniques. Several “elicitors” have been identified, but their local concentration within and around the wounding site remains to be established. For microbial, especially fungal infections many cell wall-derived compounds, such as oligosaccharides, oligoglucoronides, and degradation products of important cellular proteins have been shown to act as elicitors triggering major defense cascades. During her Ph.D. thesis Dr. A. Fiedler developed a novel technique that allowed her to blot the intact epicuticular wax layer from plant leaves to a grated ZnS window that served as a target for FT/IR- and MALDI-TOF imaging. This combined approach, allowed an in situ structure elucidation and localization of the surface compounds with ca. 100 ?m spatial resolution using the sensitive transmission mode [1]. Moreover, appropriate MALDI matrices have already been developed to monitor cell wall-derived elicitors such as oligosaccharides [2]. The current procedure can be combined with other powerful Imaging-techniques, especially linear and non-linear variants of Raman–microspectroscopy. Raman-based analytics have been successfully applied to monitor plant volatiles and wax structures in and ex vivo.[3,4] The Raman approach has the additional advantage that the plant surface can be analyzed in the reflection mode and, hence, does not require the preceding blotting step. Nonetheless, the experimental implementation and optimization of non-linear Raman microscopy – in particular CARS (coherent anti-Stokes Raman microscopy) – for online analytics of plant surfaces implies a significant experimental challenge, which will have to be met in this project. In particular, we will put special emphasize on developing a compact tailored light-source to be used for Raman-based microspectroscopic analytics. The source will base on a fiber laser pumped fiber-optical parametric amplifier, resulting in an alignment-free and extremely stable versatile tool for CARS-microscopy. This approach could give evidence to the concept that most “elicitors” for infection and herbivory represent compounds that are derived by degradation from the plant’s fundus of biopolymers. The Raman-approach will be also used to monitor and localize signaling compounds (trisporic acids and their precursors) in zygomycetes fungi. If successful, the method can be extended to parasitic interactions and to endosymbiotic fungi that promote growth in planta [6]. The interaction of plant roots with root damaging organisms would represent another novel system to be studied by Raman-based Imaging techniques. REFERENCES [1] Andrea Fiedler, Ph.D. Thesis 2009. A. Fiedler, A. Svatos & W.Boland. Plant surface analysis with local resolution by combined FT-IR and MALDI-TOF Imaging. To be submitted. [2] J. Becher, A. Muck, A. Mithöfer, A. Svatoš & W. Boland. Negative mode MALDITOF/ MS analysis of oligosaccharides using halide adducts and 9-aminoacridine matrix. (2008) Rapid Commun. Mass Spectrom., 22, 1153-1158. [3] M.A. Strehle, P- Rösch, M. Baranska, H. Schulz & J. Popp. On the way to a quality control of the essential oil of fennel by means of Raman spectroscopy. (2005) Biopolymers, 77, 44-52. [4] I. A. Weissflog, D. Akimov, B. Dietzek & J. Popp. Monitoring the distribution of epicuticular waxes by means of CARS microscopy. Manuscript in preparation. [5] D. Schachtschabel, A. David, K.-D. Menzel, C. Schimek, J. Wöstemeyer & W. Boland. Cooperative biosynthesis of trisporoids by the (+) and (-) mating types of the zygomycete Blakeslea trispora. (2008) ChemBioChem, 9, 3004 – 3012. [6] M. Schlicht, O. Šamajová, D. Schachtschabel, I. Lichtscheidl, D. Menzel, W. Boland & F. Baluška. D’orenone Blocks Polarized Tip-Growth of Root Hairs by interference with the auxin transport network. (2008) Plant J., 55, 709-717.
 
 
Duggan, Seána

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JSMC Fellow

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Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
ZIK Septomics
Research Group Fungal Septomics
PhD Project:

The interaction of Candida glabrata with human Neutrophils

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Abstract: Background Systemic infections due to Candida spp. are increasing worldwide and represent a major percentage of clinical sepsis cases. Candida glabrata is the second most common...
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... pathogen in the genus and infections caused by C. glabrata are associated with an increased mortality. In contrast to C. albicans, C. glabrata is a haploid organism and displays little to no morphological plasticity. For these reasons, C. glabrata is both a medically important pathogen and an excellent model fungus for studying innate immune activation. Own work and relevant publications The BMBF funded Fungal Septomics Research Group is part of the Center for Innovation Competence “Septomics” at the Friedrich-Schiller-University of Jena. Our team analyzes the activation of innate immune cells by pathogenic fungi with a focus on pathogenic Candida species. Effects of fungal morphogenesis on DC activation were characterized, providing evidence that these cells can recognize yeast and hyphal forms of C. albicans. We characterized a morphotype specific activation program of human PMN in response to C. albicans, resulting in targeted motility and the release of IL-8. In addition, the contribution of secreted aspartic proteases to the interaction of C. albicans with human PMN (cooperation with Prof. B. Hube, HKI Jena) and the role of ROI formation in killing of C. albicans is subject of ongoing studies. In close collaboration with A. Brakhage (HKI Jena) and J. Löffler (Würzburg), recognition of A. fumigatus by the innate immune system has been also been studied in my group. References: Hornbach A, Heyken A, Schild L, Hube B, Löffler J, Kurzai O. The glycosylphosphatidylinositol-anchored protease Sap9 modulates the interaction of Candida albicans with human neutrophils. Infect Immun. 2009 Dec;77(12):5216-24. Mezger M, Wozniok I, Blockhaus C, Kurzai O, Hebart H, Einsele H, Loeffler J.Impact of mycophenolic acid on the functionality of human polymorphonuclear neutrophils and dendritic cells during interaction with Aspergillus fumigatus. Antimicrob Agents Chemother. 2008 Jul;52(7):2644-6. Mezger M, Kneitz S, Wozniok I, Kurzai O, Einsele H, Loeffler J.Proinflammatory response of immature human dendritic cells is mediated by dectin-1 after exposure to Aspergillus fumigatus germ tubes. J Infect Dis. 2008 Mar 15;197(6):924-31. Wozniok I, Hornbach A, Schmitt C, Frosch M, Einsele H, Hube B, Löffler J, Kurzai O.Induction of ERK-kinase signalling triggers morphotype-specific killing of Candida albicans filaments by human neutrophils. Cell Microbiol. 2008 Mar;10(3):807-20. Lessing F, Kniemeyer O, Wozniok I, Loeffler J, Kurzai O, Haertl A, Brakhage AA. The Aspergillus fumigatus transcriptional regulator AfYap1 represents the major regulator for defense against reactive oxygen intermediates but is dispensable for pathogenicity in an intranasal mouse infection model. Eukaryot Cell. 2007 Dec;6(12):2290-302.
 
 
D´Souza, Glen

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IMPRS Student

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Institute/Dep.
Max Planck Institute for Chemical Ecology
Dept. of Bioorganic Chemistry
Experimental Ecology and Evolution
PhD Project:

The effect of genetic diversity on the evolution and maintenance of mutualistic interactions

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Institute/Dep.
Friedrich Schiller University Jena
Institute for Inorganic and Analytical Chemistry
PhD Project:

Metabolomische und ökologische Untersuchung der Allelopathie von Mikroalgen des marinen Planktons

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Abstract: Microalgae of the marine plankton are known to chemically interact with surrounding organisms in their ecological environment. One example for such an interaction is the communication...
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... via allelochemicals. Allelopathy is an ecological concept, with which organisms are able to influence the growth, survival and reproductive success of coexisting organisms of a different species both positively and negatively. Allelopathy thus plays an important role in shaping the dynamics of planktonic communities. Therefore it is of great interest to investigate these interactions in the ecological context and to identify the involved infochemicals. As recent research has been mainly focused on the negative effects of allelopathy, this project aims on characterizing the positive allelopathic effects. Allelochemicals will be identified via modern metabolomic techniques in combination with 13C isotope labeling of organisms and traditional bioassay-guided structure elucidation coupled with analytical structure elucidation. In order to evaluate the findings in the ecological context, mesocosm experiments will be conducted.
 
 
Ekaney, Michael

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Institute/Dep.
University Hospital Jena
Clinic of Anaesthesiology and Intensive Care Medicine
Research Unit Experimental Anesthesiology
PhD Project:

Sepsis-associated microthrombus formation: Processing and Secretion of von-Willebrand factor Cleaving protease, ADAMTS13

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Abstract: State of the Art: Activation of coagulation and deposition of (micro-) thrombi as a consequence of inflammation is well described and might be viewed as an essential part of the host...
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... defense of the body against infectious agents in an effort to contain the invading entity and the subsequent inflammatory response to a limited area [ESMON]. In line with that, the activation of systemic coagulation in combination with microvascular failure that results from the systemic inflammatory response to severe infection or sepsis contributes to development of multiple organ dysfunction. The plasma circulating metalloprotease ADAMTS13 limits formation of platelet-rich thrombi by cleaving von Willebrand factor (VWF). VWF is released as unusually large multimers from endothelial cells or platelets upon stimulation as observed in sepsis, which functions as the preferred substrate for ADAMTS13. Inability to cleave UL-VWF multimers to smaller sizes may result in its plasma abundance, leading to enhanced platelet adhesion and aggregation, profound thrombocytopenia due to platelet consumption, ultimately resulting in deposition of microthrombi and aggravation of remote organ failure [BOCKMEYER; CLAUS; MARTIN]. ADAMTS13 appears to be synthesized in liver, particularly in hepatic stellate cells, which reside in the space of Disse adjacent to the hepatocytes [UEMURA]. However, the contribution of hepatic stellate cells in regulation of plasma ADAMTS13 levels remains to be revaluated due to the fact that ADAMTS13 mRNA is detected in almost every organ tissue, suggesting that the vascular endothelium may also be a rich source of plasma ADAMTS13. There is increasing body of evidence that ADAMTS13 is synthesized and apically secreted from human vascular endothelial cells in culture and in situ; considering the enormous surface area of vascular endothelial beds, a small fraction of endothelial cells producing ADAMTS13 at any given time may contribute significantly to plasma levels of ADAMTS13 activity [TURNER, SHANG]. Consequently, any perturbation of endothelial cell function or ADAMTS13-VWF interactions at the site of their syntheses by inflammatory cytokines or cytotoxic noxes such as histones may play an important role in the pathogenesis of thrombotic complications [XU].
ADAMTS13 displays a multi domain structure, where the proximal carboxyl terminus of ADAMTS13 appears to determine substrate recognition and specificity. Two CUB1 domains at the distal C-terminus may be critical for docking of the protease to VWF under flow [TAO]. Of more interest, mutations in the CUB domains result in severe deficiency of plasma ADAMTS13 activity. In vitro studies have shown that some mutants exhibit significant impairment in secretion, since apical sorting of ADAMTS13 may depend on its association with lipid rafts through the CUB domains. Although the exact mechanism by which a soluble ADAMTS13 is associated with lipid rafts is not known, one could hypothesize that such association between the CUB domains of ADAMTS13 and rafts may be indirect, perhaps through the interactions of the CUB domains with other membrane-bound sorting receptors in the trans-Golgi network (TGN), on the vesicular carriers and/or at the apical cell surface. Removal of the CUB domains or depletion of intracellular cholesterol broke up the interactions among ADAMTS13, sorting receptors, and rafts, therefore reducing the efficacy of apical sorting [SHANG]. However, these interactions appear to be transient or may occur only intracellular, as the ADAMTS13 protease was not detected in an association with plasma membrane.
The proposed project will be performed in the lab ‘Exp. Anaesthesiology’ with long term experience in the elucidation of clinical significance of a dysbalanced ratio of VWF/ADAMTS13 ratio in patients with systemic inflammation and sepsis. The ratio was found inversely correlated with the severity of the disease and mortality. Glomerular deposition of VWF/platelet enriched microthrombi in the kidney, an organ mostly affected during the clinical course of sepsis, bridge the gap between an altered plasmatic ADAMTS13 activity in human sepsis and the missing evidence of microvessel occlusion by microthrombi. Most recent data reveal a strong reduction of mRNA-transcript encoding the protease in both, endothelial or hepatic stellate cells, stimulated with proinflammatory cytokines or serum obtained from patients with sepsis, which was nearly completely abrogated by simultaneous incubation with protein-C, activated by an unknown mechanism.
 
 
Engert, Nicole

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JSMC Fellow

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Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Research Group
Microbial Immunology
PhD Project:

Mechanisms of Candida albicans colonization and translocation

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Abstract: The opportunistic fungal pathogen Candida albicans is a common member of the normal microbiota of humans colonizing mucosal surfaces, especially the gastrointestinal tract. However, as...
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... an opportunistic pathogen, C. albicans can disseminate from the intestine and cause disseminated life-threatening diseases if the gastrointestinal balance is disturbed, e. g. by antibiotic treatment, disruption of epithelial barrier function or immunosuppression. One predisposing factor for disseminated candidiasis is major surgery. During prolonged surgery, general anesthesia induces centralization of blood flow, leading to mesenteric ischemia. Mesenteric ischemia results in local hypoxia of intestinal epithelia which leads to a damaged gastrointestinal barrier. We therefore hypothesize that mesenteric ischemia and intestinal hypoxia enhances translocation of C. albicans through the epithelial barrier and thereby contributes to the development of disseminated candidiasis. Thus, the aim of this project is to characterize the interaction of C. albicans with intestinal epithelial cells under normoxic and hypoxic conditions and to identify fungal factors important for translocation under hypoxia. Differential staining and microscopy, damage and viability assays will be performed in monolayer and trans-well assays to determine the translocation potential of C. albicans during normoxia and hypoxia. To elucidate the influence of hypoxia on the expression of fungal virulence-associated genes, microarray technologies will be used. The role of genes upregulated under hypoxia will be further analyzed using defined fungal knock out and overexpression mutants. To address the host response to C. albicans infection, transcriptional profiling and cytokine analysis will be used. Hypotheses derived from these in vitro experiments will then be tested using murine ex vivo and in vivo models. The results obtained in this project will provide insights into the molecular mechanisms of the translocation of C. albicans through intestinal barriers. This knowledge could provide the basis for the development of novel prophylactic and therapeutic strategies and might reveal potential biomarkers for risk assessment and early diagnosis.
 
 
Fabisch, Maria

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GRK1257 Student

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Institute/Dep.
Friedrich Schiller University Jena
Institute of Ecology
Dep. Aquatic Geomicrobiology
PhD Project:

Impact of heavy metals on microbial formation of iron oxides

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Abstract: In the former uranium-mining district near Ronneburg (Thuringia, Germany) acid mine drainage-impacted creeks contain high contamination with heavy metals, e.g., Cu, Co, Ni, Zn, and Cd,...
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... as well as accumulations of Fe(III) precipitates. This project focussed on Fe(II)-oxidizing bacteria (FeOB) in the former Gessenbach creek, in whose streambed upwelling and contaminated ground and seepage waters now discharge. Microbially formed Fe(III) precipitates can contribute to the retention of dissolved heavy metals and lower their bioavailability by co-precipitation or adsorption. Thus, FeOB could be useful for bioremediation in heavy metal contaminated environments. The creek sediment pH ranged from extremely to slightly acidic, providing an ideal site to study FeOB communities inhabiting different pH environments with high metal contamination. The main objectives of the project were 1) to biogeochemically characterize field sites and heavy metal distributions, 2) to investigate the resident microbial FeOB communities, dependent on pH and over a distinct flow path and over time, and 3) to examine the role of microbially formed Fe(III) precipitates in the retention of heavy metals. In the first part of the project, a detailed biogeochemical characterization of selected sites in the course of the former Gessenbach creek was done. Various creek sediments were characterized, including chemical parameters and potential rates of iron oxidation and reduction. Metals like Zn and Cu were mainly bound to the iron oxide fraction in sediments, as shown by sequential extractions. Furthermore, creek sediment material was taken to cultivate FeOB of different metabolic groups and pH values in selective media. For instance, a gradient tube technique was used to enrich microaerobic FeOB. A high heavy metal tolerance of microaerobic FeOB from Gessenbach creek sediment was demonstrated. Microbial FeOB communities were studied by cloning and quantitative PCR. Interestingly, Gallionella spp.-related bacteria were identified to dominated the FeOB communities in metal-contaminated ground and creek water and creek sediments with pHs from 4.4 to 6.3. This dominance was stable over time and along the flow path of upwelling underground mine water along the creek. Gallionella spp. are neutrophilic, microaerobic FeOB usually found in redox-gradient freshwater environments, and have recently also been reported from acid mine drainage-influenced environments, but never with such clear dominance. The interaction of FeOB with the environment, in particular with metals, is of great importance, since microbes are in direct contact not only with other bacteria, fungi, higher animals and plants, but also with the abiotic environment. They are influenced and limited by environmental factors, but at the same time change the environment by their metabolism and growth. Thus, understanding of microbial ecology and microbe-mineral interactions are of fundamental interest for microbiologists as well as geo-scientists, e.g., for the application of microbes for bioremediation.
 
 
Fatangare, Amol

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IMPRS Student

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Institute/Dep.
Max Planck Institute for Chemical Ecology
Research Group Mass Spectrometry
PhD Project:

Development of methods for visualization of metabolomic maps and fluxes in plants challenged by insect and bacteria

 
 
Ferreira Gomes, Marta

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JSMC Fellow

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Institute/Dep.
Friedrich Schiller University Jena
Center for Molecular Biomedicine
Laboratory of Cell Biology
PhD Project:

B cells and antibodies in protective immunity to Candida albicans infection

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Abstract: Candida albicans colonizes mucosal surfaces of most healthy individuals as a benign member of the human microbiota, but may become an invasive pathogen in the immunocompromized host. In...
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... the clinical setting, C. albicans is a major cause of nosocomial infections and may cause severe bloodstream invasion with mortality rates exceeding those of bacterial sepsis. Basic immunological principles that allow tolerance to this commensal on the one hand but mediate antifungal immunity on the other hand are thus investigated, with the final goal to elicit protective immune responses against this opportunistic pathogen in the human host. While in the context of acute bloodstream infection innate immune responses appear to predominate protection, adaptive immunity is required for long term immunological memory and immunization. In the gut, the major reservoir of C. albicans, the fungus may persist even though it evokes a response from both T and B lymphocytes. The present project will focus on the role of antibodies produced by B cells in the maintenance of benign C. albicans colonization, as well as in protection of individuals from secondary challenges with C. albicans bloodstream infections, to approach the question whether and how a protective antibody response to C. albicans can be triggered in humans.
 
 
Fischer, Juliane

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ILRS Student

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Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Dept. Molecular and Applied Microbiology
PhD Project:

Post-translational modifications and secondary metabolism of Aspergillus nidulans

 
 
Föge, Martin

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JSMC Fellow

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Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Dept. Molecular and Applied Microbiology
PhD Project:

Characterisation of receptors of the human-pathogenic fungus Aspergillus fumigatus - How does the fungus communicate with the environment and the host?

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Abstract: Aspergillus fumigatus is the most important air-borne fungal pathogen of humans. In individuals with immune deficiency, inhalation of conidia can cause a life threatening disease,...
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... designated invasive aspergillosis. Like every other organism, A. fumigatus has to react specifically to different environmental stimuli, for example to adapt to the availability of different nutrients, or to cope with stress. These responses are controled by receptor-mediated signal perception and intracellular signal transduction which is also important for host-pathogen interaction. Bioinformatic analysis of the A. fumigatus genome revealed the presence of 15 genes encoding putative G protein-coupled receptors. We already characterised the function of two receptor-encoding genes, gprC and gprD. Our results imply a connection of GprC and GprD to the calcineurin/calmodulin signaling pathway that is regulated by intracellular calcium levels. The phosphatase calcineurin plays a central role in regulating fungal morphology and virulence. To prove the connection of GprC and GprD to calcium signaling, intracellular calcium levels will be determined by ratiometric methods using the fluorescent dye Fura-2. By this, differences in calcium concentrations in response to different stimuli can be monitored. To specifically assign the function to single receptors, gene deletion mutants for all identified GPCRs will be generated and analysed. In a second approach, receptor ligands will be screened by expressing the GPCRs in Xenopus oocytes via mRNA injection. The activity of ion channels will be determined by patch clamp techniques. The localization of GPCR-GFP fusion proteins with confocal laser scanning microscopy to monitor receptor internalisation and recycling processes will be studied as well. By means of molecular genetic methods and bio-physical characterisation, central signaling processes will be assigned to the receptors in A. fumigatus. To date, only little is known of the role of receptors in communication with other microorganisms or with host cells. Recently, we were able to show that co-cultivation of A. nidulans and A. fumigatus with Streptomyces hygroscopicus leads to the activation of silent gene clusters. To elucidate fungal signaling processes, i.e., signal sensing, the role of receptors will be analysed by co-cultivation of S. hygroscopicus with receptor mutants. Furthermore, receptor mutant strains will be confronted with immune effector cells (alveolar macrophages, neutrophils) and the fungal response will be analysed, e.g. the fusion rate of phagosomes and lysosomes. The aim of this project is to identify A. fumigatus receptors that are essential for sensing of specific environmental stimuli and the communication with surrounding cells (bacteria, immune effector cells).
 
 
Förster, Toni

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JSMC Fellow

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Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Dept. Microbial Pathogenicity Mechanisms
PhD Project:

Identification and characterisation of translocation-associated factors of Candida albicans

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Abstract: Candida albicans is normally a harmless commensal inhabitant of mucosal surfaces, such as the human gut, but is also an opportunistic pathogen. Under certain predisposing conditions, C....
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... albicans can cause life-threatening systemic infections. This fungus is the most common cause of life-threatening nosocomial fungal bloodstream infections. By crossing the intestinal barrier, C. albicans can access the bloodstream and can cause lethal sepsis. Therefore, understanding the process of this translocation will be crucial for future therapies. The project is divided into two main parts. The first focus of this project is Ece1. Ece1 is a protein which is proteolytically processed into several short peptides, one of which acts as a pore-forming toxin. Such an activity may be crucial for translocation through host barriers. Detailed analysis of C. albicans mutants, lacking ECE1, during interactions with intestinal cells will be performed to elucidate the importance of this protein in translocation. The second part will focus on the identification of novel fungal factors and attributes required for translocation through intestinal epithelial tissue. A translocation assay for screening C. albicans mutant libraries will be established to identify new genes associated with transmigration through intestinal cells. Modified assays with gut-mimicking conditions (e.g. pH, O2) and a more detailed analysis of these new transmigration-associated genes will be carried out. Additionally, the influence of probiotic bacteria on the pathogenicity and translocation of C. albicans will be investigated. The aim here is the development of a commensal-to-pathogen switch model. The presence of bacteria inhibits the epithelial damaging activity of C. albicans. Therefore, by adding antibiotics to a co infection model of bacteria (e.g. Lactobacillae) and C. albicans, the fungus is predicted to switch to a pathogenic form. This process will be followed by transcriptional profiling of the different states during the switch from commensal to pathogen. By elucidating these different aspects of C. albicans colonisation and transmigration, a better understanding of translocation will be achieved, which may ultimately lead to novel treatment strategies to prevent candidaemia.
 
 
Freihorst, Daniela

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JSMC Fellow

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Institute/Dep.
Friedrich Schiller University Jena
Institute of Microbiology
Microbial Communication
PhD Project:

Molecular biology of ectomycorrhizal symbiosis

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Abstract: The formation of ectomycorrhiza as a symbiotic relationship between trees and basidiomycete fungi of the genus Tricholoma involves signal transfer between both partners. The detection...
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... of tree signals within the fungus leads to differentiation and formation of the structures of mantle and Hartig’ net. Genes induced upon mycorrhiza formation are thus useful as markers to detect the molecules that induce the symbiotic state in the fungus. In the project offered within JSMC we aim at the analysis of a fungal gene up-regulated during mycorrhiza development. This APS kinase is expected to be involved in sulfate acquisition and transfer between the symbiotic partners in addition to its being specifically regulated in mycorrhiza. Thus, the promotor analysis will yield insight into signal recognition with the possibility to identify the inducing substance. At the same time, over-expression of the gene in Tricholoma will allow to identify physiological states with respect to nutrient transfer between both partners. Investigations will be carried out at the Institute of Microbiology, Microbial Phytopathology, Friedrich Schiller University Jena.
 
 
Frister, Adrian

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JSMC Fellow

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Institute/Dep.
University Hospital Jena
Center for Molecular Biomedicine
Institute of Molecular Cell Biology
PhD Project:

PI3Ky as a mediator of septic encephalopathy

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Abstract: Sepsis is an uncontrolled inflammatory response of the mammalian organism on bacterial infections. The high mortality rate of the disease is caused by deterioration of many organs...
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... including brain. Septic brain impairment or encephalopathy is characterized by cell death within the central nervous system and cognitive defects. Septic encephalopathy probably arises from the action of inflammatory mediators on the brain or cytotoxic responses of brain cells to these mediators. Lipopolysaccharide (LPS), the cell-wall component of Gram-negative bacteria, induces sepsis with a number of comparable pathological sequels in humans and animals. Therefore, in rodents the disease can be mimicked by administration of bacterial LPS. PI3Kgamma is a species of the phosphoinositide 3-kinase (PI3K) family of intracellular signaling proteins, which has been depicted as a major mediator of inflammatory reactions of immune cells. The dominant regulatory function of PI3Kgamma in inflammatory processes is currently inducing substantial efforts of the pharmaceutical industry using the signaling protein as a target for the treatment of inflammatory diseases including rheumatoid arthritis and chronic obstructive pulmonary disease. Recent investigations and preliminary own work suggest involvement of PI3Kgamma in the pathogenesis of neuro-inflammatory processes. The present project aims to elucidate the contribution of PI3Kgamma to the phenotyp of septic encephalopathy. Using mice treated with LPS as a disease model the signaling activities of PI3Kgamma will be affected by genetic and pharmacological means and typical neuro-anatomical, cell biological and behavioral changes in the animals will be investigated in a comparative manner. Mutational analysis includes PI3Kgamma deficient mice and transgenic animals expressing biochemically-defined mutants of the signaling protein. Pharmacological treatment of mice administered with LPS allows comparative investigations of the effects of inhibitors specifically suppressing the enzymatic activity of the PI3K species alpha, beta, gamma and delta. In addition, these investigations may contribute to the development of novel concepts for the therapy of sepsis and it's harmful effects in the nervous system.
 
 
Funai, Benjamin

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JSMC Fellow

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Institute/Dep.
Friedrich Schiller University Jena
Institute of Microbiology
Microbial Communication
PhD Project:

Combinatorial effects in the heavy metal resistance of streptomycetes

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Abstract: Actinomycetes and especially the genus Streptomyces, have a unique ability to produce a wide range of biologically-active secondary metabolites and play an important role in the...
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... pharmaceutical and chemical industry. Due to the fact, that there has been a decline in the discovery of new metabolites from common soil-dwelling actinomycetes, the screening for new metabolites could be enlarged by extreme habitats like heavy metal contaminated sites which could offer the chance to isolate less common actinomycetes. In these habitats, microbes have to cope with rough conditions such as low pH, high concentrations of heavy metals and salts as well as low nutrient contents and therefore evolved several adaptations like heavy metal resistances and potentially new secondary metabolite pathways. Studies have shown that heavy metal stress and co-cultivation can induce a shift in the secondary metabolites pattern by activating gene clusters which are silent under standard screening conditions. By knowing this, a strain collection of actinomycete isolates originating from a former mining area will be screened for their potential to produce antibiotics and other biologically-active secondary metabolites under heavy metal stress and co-cultivation. The experiments will be carried out with different bacteria and yeast isolates as well as several heavy metals in a microfluidic system which is developed by partners of the project „BactoCat - Neue Syntheseleistungen durch Kopplung mikroorganismischer und Metallnanopartikel-katalysierter Prozesse in der Mikroreaktionstechnik 031A161B”.
 
 
Gallegos Monterrosa, Ramses

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Institute/Dep.
Friedrich Schiller University Jena
Institute of Microbiology
Junior Research Group Terrestrial Biofilms
PhD Project:

Cell-cell communication in single species and mixed biofilms

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Abstract: Background Biofilm formation costs and benefits the society. On one hand biofilms can be negative, for example, biofilms are a source of contamination in food processing equipment,...
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... can reduce heat transfer in cooling towers, increase drag on ships, foul reverse osmosis membranes and even corrode metal surfaces; moreover, since biofilms have great resistance to antimicrobial treatment, they are difficult to control in industry or the clinic. On the other hand, biofilms can be also beneficial, such as in the case of biofilm formation by Bacillus subtilis in various crop plant root systems. In most cases biofilm formation has been targeted (to prevent or to promote) by altering the ability of bacteria to attach itself to surfaces or by changing pathways involved in matrix production. Aim The current project is involved in the cell-cell communication (i.e. quorum sensing) in single- and multi-species biofilms. The role of various B. subtilis produced quorum sensing molecules will be examined during biofilm formation. Further, the role of various global transcription regulators will be examined in a novel approach based on random mutagenesis to identify the important features of these regulators during biofilm development and in quorum sensing. Finally, the current project aims to get a better insight into quorum sensing through the use of mixed species biofilms and reveal the effect that different Bacillus species may have over the development of B. subtilis biofilms. The different parts of this project will all aim to characterize and identify possible targeting of quorum sensing in bacterial biofilms that could be further exploited in medical or biotechnological settings.
 
 
Garrone, Alessio

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JSMC Fellow

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Institute/Dep.
Leibniz Institute of Photonic Technology (IPHT)
Dep. Spectroscopy/Imaging
Friedrich Schiller University Jena
Institute of Physical Chemistry
PhD Project:

Photoreaction of the NADPH-Protocholorophyllide-Oxidoreductase from Synechocystis – The Ultrafast Mechanism of Adapting a Metabolic Pathway to an Environmental Stimulus

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Abstract: Microbes - as any living organism - need to adjust their metabolism to a multitude of external stimuli a prominent one being the exposure to light, upon which biochemical pathways are...
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... regulated. The primary mechanistic step of the response is typically the photoinduced alteration of molecular structures in a photoactive protein such as rhodopsins or phytochromes. Nonetheless, there also exist two enzymes, which require the absorption of light for the catalytic function. Thereby their function can be directly triggered by the exposure to light. One of these two enzymes is the NADPH:protochlorophyllide?oxidoreductase (POR), which is known from cyanobacteria and higher plants. POR plays a central role in the light regulation of the chlorophyll synthesis. It catalyzes one of the later steps in the chlorophyll synthesis pathway: the light?dependent reduction of protochlorophyllide (PChlide) to chlorophyllide by trans addition of hydrogen across the C17?C18 double bond in the porphyrin ring. Because POR is activated by light it can provide information on the way in which light energy is used to control the enzymatic activity of living organisms in general. Within this project the mechanistic interplay between protein structure and enzyme function will be investigated on an ultrafast timescale (on the time scale of picoseconds, i.e., 10-12 s). This is done by combining mutagenesis studies of the catalytic reaction center with various spectroscopic tools such as femtosecond time-resolved differential absorption (in the UV/Vis and mid-IR spectral range) and picosecond time-resolved luminescence measurements. This combination of techniques enables the assessment of individual protein sites, which are critical for the ultrafast photoresponse of the enzyme, and the determination of the relevant reaction coordinates on an ultrafast time-scale. This is of particular interest as it has been shown previously that processes on a sub?picosecond/ picoseconds timescale determine the overall efficiency of a photodriven reaction. Additionally, comparative studies on the ultrafast reactions of PORs from photosynthetic eucaryotes will be pursued in this project in order to address the question of whether the catalytic mechanism of the light-dependent PORs has evolved from the cyanobacterial enzyme.
 
 
Grüneberg, Jan

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JSMC Fellow

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Institute/Dep.
Friedrich Schiller University Jena
Institute for Inorganic and Analytical Chemistry
PhD Project:

The symbiotic interaction of the green alga Ulva mutabilis and bacteria

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Abstract: At most sea coasts Ulva species (sea lettuce) are among the most abundant marine green macroalgae growing predominantly in the intertidal zone. But Ulva is also one of the most dominant...
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... biofoulers on man-made surfaces. It was suggested that this ecological success of the family Ulvaceae is linked to its associated bacteria. We are aware now that specific bacterial taxa are associated with green algae suggesting specific selective mechanisms. The aim of the proposed work is to explore the algal-bacterial interactions on a molecular basis. Gametophytes of Ulva mutabilis, a fast growing species, are propagated under established standardised conditions. The gametogenesis is controlled by two sporulation inhibitors, whereas the release of matured gametes is regulated by a swarming inhibitor. U. mutabilis develops only callus-like non-differentiated cells under axenic conditions. Using a bioassay guided approach the proposed project aims to purify and subsequently elucidate the structure of morphogenetic active compounds from cultures of bacteria associated with U. mutabilis. Concomitantly the hypothesis should be tested whether algal-derived dissolved organic matter and the bacterial metabolism are coupled suggesting that bacteria are selectively attracted by U. mutabilis. The task will be to decipher the multiple interactions based on algal and bacterial signal molecules using modern mass-spectrometry approaches (e.g. UPLC-MS/MS, GC-MS) paired with bioassays in phycology and microbiology. It is anticipated to investigate the ecological significance of these compounds in field experiments (tide pools).
 
 
Gusewski, Sandra

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ILRS Student

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Institute/Dep.
Friedrich Schiller University Jena
Chair of Genetics
PhD Project:

Assessing DNA-binding specificity of MADS-domain transcription factors

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Abstract: The specific molecular interaction between DNA and transcription factors (TFs) is of utmost importance to control gene expression and thereby cell differentiation and organ development....
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... Consensus sequences for DNA-binding sites have been defined for many TFs. However, more elaborate principles are still lacking that define which features turn a certain DNA sequence, which might exist in several thousand copies in the genome, into a true recognition site. It will be studied to which extent the primary DNA sequence (“base readout”) and also the sequence-dependent shape of the DNA (“shape readout”) contribute to binding specificity of a TF. To address this issue, MADS-domain proteins will be used as a model system. They are found in almost all eukaryotes, but have especially prominent developmental functions in seed plants. SEPALLATA3 (SEP3), a MADS-domain transcription factor involved in flower development, will serve as a starting point of research since this factor has already elicited considerable scientific interest. Within this project, the thermodynamics and kinetics of the molecular interactions of SEP3 with DNA will be studied, using a variety of biophysical, bioinformatics and molecular biology tools. The structural characteristics of the protein, the DNA and the protein-DNA-complexes will be determined using circular dichroism (CD) spectroscopy. Bioinformatic sequence analyses will reveal candidate amino acid residues that may be involved in determining binding specificity. Based on these results, proteins with amino acid substitutions will be generated to gain additional insights into how different residues contribute to binding specificity.
 
 
Hädrich, Anke

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GRK1257 Student

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Institute/Dep.
Friedrich Schiller University Jena
Institute of Ecology
Dep. Aquatic Geomicrobiology
PhD Project:

Iron cycling in acidic fens

 
 
Händel, Matthias

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GRK1257 Student

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Institute/Dep.
Friedrich Schiller University Jena
Institute of Geosciences
Chair for Hydrogeology
PhD Project:

Microbially mediated neoformation of iron- and manganese nanoparticular geosorbents: A spectro-

 
 
Henke, Catarina

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IMPRS Student

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Institute/Dep.
Friedrich Schiller University Jena
Institute of Microbiology
Microbial Communication
PhD Project:

Ectomycorrhizal signaling

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Abstract: Interaction of ectomycorrhizal fungi and trees is a widespread symbiosis in nature known to improve plant growth, especially under stress conditions. Together, both organisms perform...
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... important functions in the ecosystem. So far, however, the molecular processes of communication and physiology are only partly understood. In the basidiomycete fungus Tricholoma vaccinum in interaction with its compatible plant host spruce (Picea abies), it has been shown that an aldehyde dehydrogenase gene, ald1, is specifically expressed. Ald1 of T. vaccinum was proposed to be enrolled in phytohormone production (auxin/indole-3-acetic acid, IAA), likewise functioning in the detoxification of aldehydes and alcohols such as ethanol, which are found in mycorrhiza habitats under stress conditions like water-logging (anoxia), in ageing and diseased plants. With this PhD project offered within the IMPRS, function analysis of fungal aldehyde dehydrogenases in T. vaccinum is intended, especially both getting a better inside into the IAA biosynthesis in T. vaccinum and investigating IAA transport in ectomycorrhizal fungi. Ethanol detoxification could be proven since overexpressing ald1 mutants showed increased ethanol stress tolerance. In the T. vaccinum genome seven further ald genes could be annotated, which are analyzed by qPCR for induction by chemical triggers like alcohols, aldehydes and biotic signals. To link between systemic reactions of the tree to one or more specific root factors, like mycorrhiza, a volatile collection system was developed, which allows us to characterize changes in the volatile pattern of young coniferous trees. With this study, our understanding of the communication pathways between organisms should be extended, which will affect also phytosanitary applications.
 
 
Hennicke, Florian

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JSMC Fellow

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Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Junior Research Group
Fundamental Molecular Biology of Pathogenic Fungi
PhD Project:

Analysis of environmental signalling and morphogenetic control in the human pathogenic yeast Candida albicans

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Abstract: Candida albicans is a major fungal pathogen which causes mucosal infections and life-threatening deep mycoses in immunocompromised patients. Interestingly, most C. albicans infections...
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... are endogenous, and humans and warm-blooded animals are the only known natural reservoir of this fungus. C. albicans can be found in almost every second individual as a harmless commensal in the gastrointestinal tract. During the course of infection C. albicans is highly versatile and successfully encounters multiple and diverse host niches, thereby facing various environmental signals. Upon such stimuli, the fungal cells employ complex regulatory networks including transcription factors which control distinct gene expression patterns. In turn, coordinately regulated response mechanisms allow the microorganisms to adapt to altered growth parameters. Major phenotypic response mechanisms include the reversible switch between C. albicans yeast and hyphal growth phases both of which are observed in infected tissue. An enigmatic species specific, morphologic characteristic of C. albicans is the ability to develop chlamydospores which however are usually not detectable in the human host but only during growth of the fungus on certain plant seed extracts in the laboratory. The complex control of signalling and response mechanisms in C. albicans is not fully understood and needs further analysis on the molecular level. In this study not yet investigated stimuli will be analyzed for their possible implication in the life-cycle and morphogenetic development of C. albicans. Natural products will be included which might influence the growth behaviour of C. albicans in the human intestine, i.e. diverse microbial, animal and plant materials. These studies should not only contribute to a better understanding of C. albicans pathogenicity, but may also enlighten adaptation mechanisms which support commensalism, a potential prerequisite for infection by this microorganism.
 
 
Hirth, Matthias

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JSMC Fellow

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Institute/Dep.
Friedrich Schiller University Jena
Institute of General Botany and Plant Physiology
Junior Research Group 'Molecular Botany'
PhD Project:

The metabolic profile of the marine microalga Ostreococcus tauri

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Abstract: With its cosmopolitan distribution and capability to form blooms, the unicellular marine alga Ostreococcus is of ecological significance [1]. Since it has a small diameter (ca. 1...
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... Mikrometer) and genome size (12.6 Mb), it has been speculated that O. tauri may represent a minimal version of a photosynthetic eukaryote [1]. At the metabolic level, Ostreococcus is hardly characterised to date. In the first part of this project, the metabolic profile of O. tauri will be described under different growth conditions. These conditions include growth under constant light, light-dark cycles, circadian conditions and iron starvation. In collaboration with Georg Pohnert (Friedrich Schiller University, Jena), cellular extracts will be analysed by gas chromatography coupled with mass spectrometry (GC-MS) by exploiting a newly devised protocol [2]. This method involves derivatisation by methoxymation/silylation, which enables the detection of a variety compounds such as amino acids, fatty acids, alcohols or sugars. Compounds will be identified by matching mass-spectrometric fragmentation patterns with database entries, and interesting compounds will be confirmed by comparison with a standard. The results will lay the foundation for further metabolic investigations in Ostreococcus. In the second part of this project, the metabolic profiles of various O. tauri regulatory mutants will be examined and compared to the profile of the wild type. Mutants will be obtained from François-Yves Bouget (Observatoire Océanologique in Banyuls-sur-Mer, France). The characterisation of these mutants at the physiological and metabolic levels will elucidate how regulatory networks control metabolism in O. tauri. This project is an essential step to understand how this ecologically important alga adapts to changes in environmental conditions, and to engineer algae for biotechnological applications such as the production of high-value compounds. [1] Derelle, E., et al., Genome analysis of the smallest free-living eukaryote Ostreococcus tauri unveils many unique features. Proc. Natl. Acad. Sci. U. S. A. 103, 11647-11652 (2006). [2] Vidoudez, C. and G. Pohnert, Comparative metabolomics of the diatom Skeletonema marinoi in different growth phases. Metabolomics 8, 654-669 (2012).
 
 
Hofmann, Janine

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JSMC Fellow

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Institute/Dep.
Max Planck Institute for Chemical Ecology
Dept. of Bioorganic Chemistry
PhD Project:

Chemical ecology of Actinomyces – induction of secondary metabolism

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Abstract: Actinomyces are well known producers of invaluable bioactive natural products such as antibiotics, that are usually obtained from pure cultures grown in liquid medium under optimized...
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... growth conditions. In contrast, in their natural environment many microorganisms have to cope with abiotic and biotic factors that influence their life style. Microorganisms interact with other microorganisms and macroorganisms. We aim to understand how Actinomyces coordinate their life and secondary metabolism in response to their environment. Hereby chemical signals e. g. quorum sensing signals and the resulting secondary metabolites play a crucial role. To investigate the chemical basis for such signalling processes and their ecological consequences a broad range of techniques (e. g. mass spectrometry, NMR, synthesis, reporter organisms, mutagenesis) will be applied.
 
 
Horbert, Peter

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JSMC Fellow

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Institute/Dep.
Leibniz Institute of Photonic Technology (IPHT)
Dep. of Nanoscopy
PhD Project:

Lab-on-a-Chip devices for investigation of microbial communication

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Abstract: The research project MikroPlex explores the basics of different fast-screening methods for the identification of bacteria and mushrooms and their secondary metabolites in complex media...
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... like foodstuffs and soil. Within the joint project the IPHT microfluidics group contributes the development, preparation and delivery of disposable Lab-on-a-Chip components and technical assistance in performing the assays and information readout. Main objectives are the implementation of sample preparation procedures for cell separation, the enrichment from analytical samples and the application of technologies for generation of pure cultures from mixtures of microorganisms. Therefore, microfluidic operation units are developed and integrated into disposable lab-on-a-chip devices. These lab-on-a-chip devices are microfluidic networks of operation units, intercomnected by microchannels. A particular process protocol can be implemented by appropriate integration of the required operation units. Recently, operation units for segment generation, dosing of liquid into droplets, phase separation, droplet merging and droplet aliquotation are available for integration into Lab-on-a-Chip devices using the approved IPHT all-glass Technology. Prototypes, developed and prepared by all glass technology can be directly transferred to mass fabrication using rapid, cost efficient replication technologies.
 
 
Hsieh, Shih-Hung

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JSMC Fellow

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Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Junior Research Group
Microbial Biochemistry and Physiology
PhD Project:

Interaction of Aspergillus terreus with dendritic cells

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Abstract: Dendritic cells, professional antigen presenting cells, are important immune cells to turn on adaptive immune responses on the one hand and provide innate immune protection on the other...
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... hand. Upon phagocytosing pathogens, dendritic cells become active to produce inflammatory cytokines and migrate to draining lymph nodes, which directly leads to T cell cytokine production. In a later phase it also leads to antibody secretion by B cells. Fungal pathogens appear largely recognized by dendritic cells through pattern recognition receptors such as TLR2, TLR4, mannose receptor and dectin-1. This further triggers dendritic cell maturation and migration during fungal infection. In our previous studies, we showed that Aspergillus terreus and Aspergillus fumigatus present different levels and compositions of cell wall antigens and display different survival strategies after phagocytosis by macrophages. Aspergillus fumigatus hides from phagocytosis, tends to inhibit acidification of phagolysosome and escapes by macrophage piercing hyphae. By contrast, Aspergillus terreus is rapidly phagocytosed by increased exposure of beta-1,3-glucan and galactomannan on the surface. Furthermore, phagolysosome acidification is not inhibited and conidia remain trapped in a resting albeit viable state. Although both, macrophages and dendritic cells, are antigen presenting cells they can show differences in their specific immune reactions even to the same pathogen. During A. fumigatus infection, dendritic cells become activated and express co-stimulated molecules and inflammatory cytokines. Due to the inactive behavior of A. terreus in macrophages, this response is much less pronounced. Thus, we believed that A. terreus may also display different strategies during the interaction with dendritic cells. To address this issue, monocyte-derived dendritic cells will be studied for their specific response towards A. fumigatus and A. terreus to analyze their impact in combating infection.
 
 
Jaradat, Sameh

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JSMC Fellow

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Institute/Dep.
University Hospital Jena
Dept. for Dermatology
PhD Project:

Defensins and infectious skin diseases

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Abstract: Most living organisms are constantly exposed to potentially harmful pathogens through contact, ingestion and inhalation. Endogenous peptides provide fast and effective means of defence...
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... against pathogens (Barra and Simmaco, 1995; Lehrer and Ganz, 1999; Reddy et al., 2004). Defensins are small cysteine-rich cationic peptides that have antimicrobial properties against many gram-positive and gram-negative bacteria as well as some fungi and viruses (Zeya and Spitznagel, 1966; Ganz et al., 1985; Ganz and Lehrer, 1995). Two classes of human defensins, ? and ?, have been identified according to placement pattern and connectivity of cysteine residues. Cells of the immune system contain these peptides to assist in killing microbes by creating pores or disrupting the microbial cell membrane allowing the release of their cellular contents (White et al., 1995; Hoover et al., 2000). ?-Defensins are expressed by granulocytes, certain lymphocytes, and intestinal Paneth cells; while ?-defensins are expressed by epithelial cells (Harder et al., 1997, 2001; Ouellette and Bevins, 2001). High concentrations of ?-defensins have been found in extracts of the scales of psoriasis patients (Hoover et.al., 2001), that may account for their low rate of skin infections. Moreover, psoriasis has been shown to be associated with increased ?-defensin gene copy number (Hollox et al., 2008). Complex gene expression changes, gene polymorphisms, and environmental factors play a key role in the predisposition to diseases. So far, an association of ?-defensin-1 gene polymorphisms with Pseudomonas aeruginosa airway colonization in cystic fibrosis has been reported (Tesse et al., 2008). Pseudomonas is a genus of gram-negative gamma proteobacteria. Pseudomonas aeruginosa is increasingly recognized as an emerging opportunistic pathogen of clinical relevance, for example the bacterial infection in cystic fibrosis patients is limited to a relatively restricted spectrum of pathogens of which P. aeruginosa represents the most prevalent organism (Burns et al., 2001). On the other hand, several different epidemiological studies indicate that antibiotic resistance is increasing in clinical isolates (Van Eldere, 2003). Staphylococcus epidermidis, gram-positive cocci arranged in clusters, is frequently causing infections in patients whose immune system is compromised. S. epidermidis often shows resistance to a wide variety of antibiotics, including penicillin and methicillin. Furthermore, fungal skin infections cause a wide range of diseases in humans. Dermatophytes, which primarily affect the stratum corneum, cause erythema and scaling of the skin. A common example is Tinea versicolor, a fungal infection that affects the skin of young people. Jensen et al (2007) observed profound changes in skin structure and barrier function, epidermal proliferation, and differentiation including pronounced ?-defensin-2 expression in Tinea corporis. This study will address the question whether variations in defensin gene copy number does influence the individual patient susceptibility to infectious skin diseases.
 
 
Jaschinski, Tino

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JSMC Fellow

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Institute/Dep.
Friedrich Schiller University Jena
Institute for Inorganic and Analytical Chemistry
PhD Project:

Investigation of dynamic changes in the chemospheres of planktonic algae

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Abstract: Phytoplankton comprises all photosynthetically organisms (mostly unicellular algae), which are freely floating in the open water. Planktonic algae are important primary producers...
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... contributing to nearly half of the total global carbon fixation. Moreover, these algae provide the bulk of food for herbivores and are thus at the base of the marine and fresh water food chains. Life in the seemingly homogeneous environment of the open ocean is very complex and in average situations thousands of different species can be observed in a liter of seawater. Early investigations were based on the assumption that species composition of the plankton is mainly controlled by the availability of nutrients and the presence of predators. In recent years we nevertheless realize that chemically mediated interactions between the organisms of the plankton have the potential to substantially influence species composition as well. Identified functions for chemical signals in phytoplankton include defensive metabolites, allelopathic compounds influencing the interactions between competitors, signals from herbivores inducing changes in the toxicity of phytoplankton, phytoplankton exudates influencing the food finding of herbivores, and even metabolites synchronizing cell death in plankton blooms.(1) Most of these functions of infochemicals have been identified in laboratory bioassays and confirmed by correlative observations in the plankton. Nevertheless, the addition of a single active compound to a culture or the detection of a compound from a water sample does not tell much about the actual situation in the plankton. Two additional major variables have to be considered if we want to predict the actual effect of infochemicals in the water: • unicellular algae change the pattern of released chemicals over time, which results in major differences in the chemical space surrounding the alga on a daily or maybe even hourly basis.(2) • release of chemicals from a unicellular organism might result in high local concentrations and patchy distributions of secondary metabolites in the water surrounding the cells or in the open ocean in times of algal blooms.(3) In this joint project we want to combine structural analytics based on mass spectrometry and NMR techniques with linear and non-linear vibrational microspectroscopy to identify and quantify metabolites in the surrounding of unicellular algae and in the water during algal blooms. We want to deduce structure, release kinetics and local concentrations of candidate infochemicals and then verify their function using elaborate bioassays. Work plan We have already set up analytical methods based on techniques derived from metabolomics research to profile the chemicals released by diatoms.2,4 Results from these studies indicate that during certain days of the life of a cell or a culture a massive release of specific metabolites can be observed. These studies were performed with two diatoms, Skeletonema costatum, which is a common model organism in ecological studies and Thalassiosira pseudonana, the first diatom with a sequenced genome. A rough estimate gives more than 100 compounds that are released into the water column. Of those only few structures are known and a first task will be to identify the structure of selected metabolites. Selection criteria will be i) release of metabolites only during a short time period of a microalgal development (this approach is motivated by the rationale that infochemicals relevant in cell-cell communication will most likely not unspecifically accumulate during normal growth of an algal bloom), ii) induction of release of specific metabolites by potential signals as it is found during induced defence5, iii) induction of release during biological interaction of the alga with, e.g., competitors or herbivores. This approach will be supported by microarray techniques, carried out in collaboration with scientists from the marine genomics initiative. Identified regulated genes will guide the search for candidate structures. Once the structures are elucidated we plan to use vibrational and multi-photonmicrospectroscopic techniques to investigate local distribution in the immediate surroundings of the cells. When working in aqueous environment especially Raman based technologies like micro Raman spectroscopy and CARS microscopy that have been already successfully applied to investigations of single bacteria or yeast cells and the local profiling of metabolites in complex mixtures will be used.6-8 Method development has to focus on the undisturbed investigation of the laminar layer of water in close vicinity of the cells. In addition to the investigation of these model organisms we want to focus on mucus producing diatoms, such as Coscinodiscus spp., that are embedded in a surrounding of exuded saccarides. Here it will be of special interest if increased accumulation of secondary metabolites can be observed within the close vicinity of the cells. The above studies will give an insight into the chemical space surrounding unicellular algae in plankton. With information on structures and local concentrations of secondary metabolites from the microalgae, we want to develop bioassays that will allow testing the impact of microscopically small point sources of chemicals in the plankton. We plan to coat chemicals on neutral particles – an approach that was already successfully applied in our lab9 and use these particles in bioassays. Topics that will be addressed are the role of chemical signals i) in the induction of resting stages during diatom blooms,(4) ii) in the regulation of feeding activity from herbivores (Barofsky et al. J. Plankton Res. under revision) and iii) in the interaction with microorganisms from the picoplankton. Relevant bioassays have been established in the lab of GP. Transfer of bioassays to larger mesocosm studies that allow enclosing and manipulating complex plankton communities is also envisaged and will be carried out within the framework of the European infrastructure program www.mesoaqua.eu.
 
 
Jo, Emeraldo

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JSMC Fellow

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Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Junior Research Group
Chemistry of Microbial Communication
PhD Project:

Mechanisms of adhesion and modulation of human immune cells by Candida albicans

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Abstract: The human pathogenic yeast Candida albicans (C. albicans) responds and inhibits host innate as well as adaptive immune reactions. This project aims at elucidating the mechanisms of...
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... immune responses by human monocytes and macrophages to C. albicans. Novel microbial proteins will be defined that alone or together with recruited human plasma proteins modulate opsonizastion and cell interaction. Complement cleavage products are the natural ligands of complement receptors CR3 and CR4 expressed on human monocytes and macrophages. The characterization of the molecular and the cellular interplay, on the level of single molecules and cells, will be carried out and developed into a bioinformatics-based infection model, that will offer novel theapeutic targets for treatment.
 
 
Kämmer, Philipp

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JSMC Fellow

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Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Dept. Microbial Pathogenicity Mechanisms
PhD Project:

Infection-associated genes of Candida glabrata

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Abstract: Candida glabrata is a commensal of humans which readily colonizes mucosal surfaces like in the gastrointestinal tract. In healthy individuals, these yeasts exist as a harmless part of...
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... the normal microbial flora. However, C. glabrata is also a successful opportunistic pathogen, which can cause infections ranging from superficial mucosal to disseminated via the blood stream, causing severe diseases with a high mortality rate. In terms of oral, vaginal and uri-nary tract infections, C. glabrata has emerged as the second most frequent fungal species after C. albicans. Despite its generic name of Candida, C. glabrata is phylogenetically more closely related to the harmless baker’s yeast Saccharomyces cerevisiae than to other pathogenic Candida species. Additionally, the strategies of C. glabrata to evade and escape the human immune system differ in fundamental aspects from C. albicans. The virulence of C. glabrata is there-fore most likely based on genetic factors which are modified for pathogenic characteristics or which are not found in S. cerevisiae and C. albicans at all. Although the genome sequence of C. glabrata is available, the function of many genes and their role in pathogenicity are still unknown. To identify infection-associated genes of C. glabrata, we use transcription data obtained under infection-simulating conditions and ana-lyze genes which we found to be C. glabrata-specific in silico. The combination of these two methods will define genes which are infection-associated and at the same time specific for C. glabrata. These candidate genes will be analyzed in more detail using established in vitro and in vivo methods to define their biological role.
 
 
Kirstein, Jens

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publications »

IMPRS Student

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Institute/Dep.
Friedrich Schiller University Jena
Institute of Geosciences
General and Historical Geology
PhD Project:

Timing of long-term carbonate mobilisation in a limestone aquifer

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Abstract: The Thuringian Basin in the central part of Germany exposes deposits of the German Triassic Muschelkalk sequence consisting of limestone and dolostone beds. Partial dissolution,...
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... oxidation and iron redistribution is obvious in limestones along the slopes of the Saale valley (e.g., quarry Bad Kösen). These features are most prominent close to a Mid Quaternary valley floor (Elster terrace), decrease down-section following fractures, and reach a minimum close to the present groundwater table in a topographic level close to the present valley floor. This example of carbonate weathering transformation includes microbial influence on reprecipitation and intermediate storage of carbonate lining fault planes. Furthermore, this location has the important advantage that the timing of the 100 m depression of the ground water table, spread over >700 Ka, has a good age control due to both topographic dating of terrace formation and optically stimulated luminescence dating (OSL dating) of former river sediments that cover these terraces. The purpose of this case study is to define and quantify the important processes of carbonate weathering on a geological time scale and to assess the rates of material transfer involving CO2 over time.
 
 
Klein, Angela E.

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JSMC Fellow

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Institute/Dep.
Friedrich Schiller University Jena
Institute of German Linguistics
PhD Project:

Versatile nano characterization methods based on multi-channel tip scanning

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Abstract: The goal of the proposed research project is the development and application of new nano-characterization methods based on multi-channel nano-tip scanning techniques. The basis of the...
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... approach is our ability to control simultaneously two scanning tips in a versatile and unique characterization setup. As compared to standard single tip systems this offers three principle advantages. Firstly, one has the unique ability to characterize system responses with nano resolution for nanoscopic excitations. Hence, one is able to measure point-spread-functions with nano resolution. Secondly, one can characterize a large number of system parameters simultaneously with nano resolution, as, e.g. optical intensity, optical spectrum, surface topology, local binding forces, temperature, pressure, electrical potential, etc. The third principle advantage of a multi-tip system consists in the ability to manipulate nano-scaled targets under live control. The work is supposed to contain fundamental research on the development of new methods for nano characterization and manipulation which are the expertise of the Institute of Applied Physics and the Fraunhofer Institute for Applied Optics and Precision Engineering. In addition there will be a strong part devoted to the application of the methods in the interdisciplinary context of the primary science case of JSMC together with collaborating partners. This will ensure the overall quality of the proposed research, by combining our state-of-the-art nano-technologies with the qualification of the partners in the other disciplines required to contribute to the study microbial communication. Standard techniques, which can be used in combination, include AFM (Atomic Force Microscopy for topology measurement), SNOM (Scanning Nearfield optical Microscopy for intensity and spectral measurement), STM (Surface Tunneling Microscopy for tunneling current measurement), tip-apex temperature measurement and heating, as well as confocal microscopy. An example of the unique abilities of the setup is surface guided confocal microscopy in which AFM topology measurement controls the confocal surface position in e.g. Raman spectroscopy. Advanced methods can also include time resolved fs techniques, tip enhanced Raman, electrical conductivity, and nano pipettes for manipulation and pressure measurements. One fundamental physical problem of current SNOM techniques is the limited transmission of available SNOM probes, which display a tradeoff between transmission and resolution. For the proposed optical techniques this imposes severe restrictions on the accessible signal to noise figures. This fundamental problem will be approached by a new tip design based on surface plasmon super-focusing, which will potentially realize high throughput nano-probing with unprecedented parameters.
 
 
Klippstein, Carolin

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JSMC Fellow

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Institute/Dep.
University Hospital Jena
Septomics Research Centre
PhD Project:

The role of E. coli-induced alterations of the Ubiquitin-Proteasome-System (UPS) for the Innate Immune Response and function of the human endothelium

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Abstract: Sepsis occurs as a result of a complex interaction between the microorganism and the host immune response. There is growing evidence of the pivotal role of the endothelium in the...
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... pathophysiology of sepsis. Systemic activation of the endothelium is characterized by the secretion of pro-inflammatory cytokines, overexpression of cell adhesion molecules with subsequent recruitment of leukocytes at non-infectious locations (1). Recent data indicate that E. coli is the most frequent pathogen isolated in patients with sepsis that is associated with an increased mortality rate. The Ubiquitin-Proteasome-System (UPS) represents the most important non-lysosomal cellular protein degradation machinery. Its function is tightly connected with the timely degradation of regulatory proteins, the elimination of misfolded proteins to restore cell homeostasis (2). Since this might be an important feature of counteracting endothelial and tissue damage during sepsis, we will investigate the composition of the UPS in endothelial cells following infection with E. coli in vitro and in a knock-out mice model lacking particular components of the UPS. Own work and relevant publications The BMBF funded Host Septomics Research Group is part of the Center for Innovation Competence “Septomics” at the Friedrich-Schiller-University of Jena. Our team analyzes the pathogen-host interactions with a strong focus on the host’s innate responses. The project will be accomplished in close collaboration with Prof. Dr. Ulrike Seifert, Institute of Immunology, University of Madgeburg. Her work focusses on the investigation of the UPS in innate and acquired immunity (2,3). Our own work focusses on host-pathogen interactions in the airways of the human lung. We investigate the mechanisms of innate immune responses of the human host after infections with bacteríal infections (4). References: 1. Anas A., Wiersinga A., de Vos A., van der Poll T. Recent insights into the pathogenesis of sepsis. J Med. 2010 2. Seifert U, et al. Immunoproteasomes preserve protein homeostasis upon interferon-induced oxidative stress. Cell 2010;142:613-24 3. Kloetzel PM. Antigen processing by the proteasome. Nat Rev Mol Cell Biol. 2001;2:179-87. 4. Slevogt H. et al. CEACAM1 inhibits Toll-like receptor 2-triggered anti-bacterial responses of human pulmonary epithelial cells. Nat Immunol. 2008; 9:1270-78.
 
 
König, Stefanie

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publications »

JSMC Fellow

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Institute/Dep.
Friedrich Schiller University Jena
Institute of Pharmacy
Dep. of Pharmaceutical / Medicinal Chemistry
PhD Project:

Mode of action and target identification of fungal secondary metabolites

 
 
Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Research Group Applied Systems Biology
PhD Project:

Image data analysis of the spatio-temporal interaction between immune cells and human-pathogenic fungi

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Abstract: This PhD project is part of the SFB/TR 124 FungiNet on “Image data analysis and agent-based modeling of the spatio-temporal interaction between immune cells and ...
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... human-pathogenic fungi” (Project B4). A comprehensive data basis of infections with human-pathogenic fungi will be acquired within this SFB/TR at the level of imaging the spatial dynamics of infection processes. To gain more insight into the infection biology of human-pathogenic fungi, differences in the interaction of Aspergillus fumigatus and Candida albicans with the immune cells of the host will be analyzed. Such a comparative analysis requires a quantitative image data analysis that is performed in an automated fashion and that will be developed in this project. The development of algorithms for the automated analysis of image data from microscopy experiments on the host-pathogen interaction is a challenging task, which has to be solved for snapshot data as well as for time-lapse data, where the latter contain dynamic properties that require tracking analyses. Our strategy is to apply various approaches of image data analysis in a comparative manner. Based on our preliminary work, we will advance algorithms that were developed within the professional software environment Definiens® which is available at the HKI. In addition, guided by the application of the professional software, we aim at solving the challenging task of object segmentation and classification by self-developed algorithms that either follow pixel-based approaches or make use of machine learning methods based on probabilistic generative models. The development of novel algorithms will be followed by a quantitative validation using training data that are also manually evaluated by human experts. A systematic mutant screening of phagocytosis assays for A. fumigatus and C. albicans will be performed and a quantitative comparison will be achieved by computing phagocytosis ratios to characterize the activity of phagocytes as well as morphological aspects with regard to the mutant aggregation and adhesion behaviour. Similarly, in the case of invasion assays, high-content screening will be applied to characterize morphological changes of the fungi with time. Finally, the analysis of time-lapse image data will reveal the dynamic behavior of phagocytes in terms of parameters that characterize their motility and activity. This will allow quantifying characteristic properties of host-pathogen interactions in order to define different stages of interaction during an immune response and to identify elements important for the recognition of fungal pathogens.
 
 
Kröber, Antje

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publications »

JSMC Fellow

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Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Junior Research Group
Fundamental Molecular Biology of Pathogenic Fungi
PhD Project:

Functional analysis of major transcriptional regulators in pathogenic dermatophytes

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Abstract: Dermatophytes are a specialized group of filamentous fungi which exclusively infect keratinized host structures (skin, nail and hair). Despite the high prevalence of the disease,...
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... dermatophytosis, little is known about the pathogenicity of these microorganisms at the molecular level. The zoophilic species Arthroderma benhamiae has become a useful model organism for the research on pathogenic dermatophytes in our laboratory for several reasons. Global gene expression data and full genome sequences of A. benhamiae have become available, and a highly efficient genetic system for the construction of gene knock-outs was recently established. The discovery and functional analysis of major transcriptional regulators and related effector genes has allowed important insights in the basic biology and pathogenicity of various pathogenic fungi, such as Candida albicans or Aspergillus fumigatus. Yet, such studies remain elusive in dermatophytes. Therefore, the envisaged project sets out to characterize the role of selected, putative transcriptional regulators in dermatophytes. Comparative genomic approaches in dermatophytes and other fungi will be applied for the identification of both orthologues of known transcription factors and hypothetical, dermatophyte specific regulators. Mutants in the identified genes will be constructed in A. benhamiae and phenotypically analyzed under various growth conditions. Thereby, basic phenotypes will be investigated, which are related to growth, morphology, sexual development and interspecies communication. In particular, the analysis of morphogenetic development will address the formation of various growth forms such as filaments, microconidia, macroconidia, chlamydospores and cleistothecia, all of which can be produced in A. benhamiae under laboratory conditions. The functional analysis of transcriptional regulators will also address the response of the fungal cells upon various environmental stimuli (temperature, pH, etc.) and the interaction with selected bacterial species (soil saprophytes, commensals of animal and/or human skin). The planned project should provide fundamental molecular insights into the biology of human pathogenic dermatophytes. This knowledge appears to be of eminent importance for a better understanding of general host and environmental adaptation mechanisms of these major important fungal pathogens.
 
 
Kruse, Stefan

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publications »

JSMC Fellow

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Institute/Dep.
Friedrich Schiller University Jena
Institute of Microbiology
Dep. Applied and Ecological Microbiology
PhD Project:

Syntrophy in co-cultures with Sulfurospirillum multivorans: Bidirectional interspecies hydrogen transfer in the energy metabolism

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Abstract: Many bacterial species living in microbial communities interact with each other through the exchange of metabolic products. In anoxic environments, hydrogen is an important metabolite...
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... that is transferred from a hydrogen producing fermentative organism to a hydrogen consuming microorganism. The interspecies hydrogen transfer is the most abundant form of syntrophy under anaerobic conditions. It is usually very important for both syntrophy partners. Hydrogen production by fermentative bacteria and hydrogen oxidation by organisms using this metabolite as electron donor are catalyzed by enzymes designated hydrogenases [1]. The organohalide-respiring epsilonproteobacterium Sulfurospirillum multivorans [2] produces hydrogen when grown on fermentable substrates in the absence of organohalides and utilizes hydrogen as electron donor in the presence of tetrachloroethene as electron acceptor for energy conservation via organohalide respiration. This indicates that the organism may act as a syntrophy partner in both functions, namely hydrogen production and hydrogen consumption. Little is known so far about syntrophy with epsilonproteobacteria, despite their high abundance in a variety of ecosystems, which was discovered recently. S. multivorans harbors genes coding for four different hydrogenases, two putative hydrogen-oxidizing enzymes (MBH, Hup) and another two possibly involved in hydrogen production (Ech, Hyf) [3]. The project will focus on the possible role of S. multivorans in syntrophic associations as a hydrogen producer or a hydrogen consumer and on the physiological function of the hydrogenases. Cocultures will be established on the one hand with a typical hydrogen producer (i.e. a fermenting bacterium) for example with lactate as electron donor and on the other hand with obligate hydrogen oxidizers such as methanogens or obligate organohalide-respiring bacteria (OHRB) [4]. The latter coculture would considerably extend our knowledge on the substrate spectrum with respect to the electron donors that may be utilized for reductive dechlorination in environments contaminated with organohalides. This coculture may even be able to completely dechlorinate compounds that cannot be dechlorinated by only one of the syntrophy partners (e. g. tetrachloroethene to ethene) [5]. The hydrogenases of S. multivorans, especially the uptake hydrogenases, will be purified and kinetically characterized.
 
 
Kuhlisch, Constanze

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JSMC Fellow

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Institute/Dep.
Friedrich Schiller University Jena
Institute for Inorganic and Analytical Chemistry
PhD Project:

Signals and metabolic changes causing phenotypic plasticity in phytoplankton

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Abstract: The project will address the hypothesis that morphological changes in unicellular pyhtoplankton resulting in colony formation follow a substantial metabolic reprogramming of the cells,...
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... which, in turn, is under the control of multiple external stimuli. Studies will apply mass spectrometry based metabolomic methods, structure elucidation of the metabolites involved in aggregation, microscopic analysis, and in situ mesocosm and shipboard experiments. The project will focus on two major model species, Phaeocystis sp. and Skeletonema marinoi and will be conducted within an international collaborative network. Unicellular algae of the phytoplankton can respond to the presence of herbivores and conspecifics by the formation of colonies or chains. The effects of this variability can be considerable since sinking velocity, nutrient uptake and also palatability to specific herbivores is strongly dependent on the size of the free floating organism in the water. Phaeocystis sp., that often contribute substantially to the phytoplankton biomass of the oceans, can form solitary cells of 4-6 µm and colonies that can reach up to 30.000µm in diameter dependent on the presence of specific herbivores (Long et al. 2007). In diatoms like Skeletonema marinoi switches from unicellular growth to chain formation can be observed that are apparently also under the control of external stimuli. While these processes are quite well understood in terms of their effects on nutrient uptake, feeding processes, and plankton dynamics, the underlying regulative principles and physiological changes are still poorly understood (Serizaqa et al. 2008; Tang et al. 2008). In this project the hypothesis is addressed that such changes in morphology go ahead with a substantial metabolic reprogramming of the cells, which is under the control of multiple external stimuli including signals from herbivores and conspecifics. In Phaeocystis colony formation is apparently dependent on mucus formation by excretion of polysaccharides (van Rijssel et al. 2000) while diatoms rely on altered cell morphology for chain formation. Studies in this project will focus on two major model species starting with an investigation of induced exudate formation of Phaeocystis sp. and extending the research to the diatom Skeletonema costatum. Both algae are grown and manipulated in the lab under standard culture conditions. Mass spectrometry based chemical profiling of extra- and intracellular metabolites related to unicellular or colonial cell stage will reveal major differences within the algal metabolome. Signals released by herbivores that are known to promote or inhibit cell aggregate formation (Long et al. 2007) will allow to regulate metabolic pathways. Further structure elucidation of characteristic metabolites will be based on high-resolution mass spectrometry and large scale purification/NMR. Moreover collaboration with the University of Bergen enables the monitoring for chemical signal production during fjord mesocosm experiments and during an anticipated cruise to the Barents Sea. Thereby, metabolic events can be correlated to growth stage, colony formation and predation. Relevant compounds could be identified, purified and used for further bioassays. Skeletonema marinoi will be investigated in a similar way.
 
 
Institute/Dep.
Friedrich Schiller University Jena
Institute of Microbiology
Microbial Communication
PhD Project:

Application of yeasts and yeast-like fungi in the bioremediation of heavy metal contaminated soil

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Abstract: Until now only a small part of the synthetical skills of microorganisms is used in biotechnological applications. For this purpose the project „BactoCat – Neue Syntheseleistungen...
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... durch Kopplung mikroorganismischer und Metallnanopartikel-katalytischer Prozesse in der Mikroreaktionstechnik 031A161B“ was founded, which uses a microfluidic system for high-throughput screening to test microbial environmental isolates. Employing various biotic and abiotic conditions, these are screened for their ability to produce utilizable secondary metabolites. One group of potentially useful organisms, which will be screened in this project, is represented by yeasts. Some species of these unicellular fungi are able to produce a lot of different metabolites, which e.g. can affect the plant growth or have antibiotic properties. Therefore some of them were already used as biological fertilizers or for the biological control of postharvest disease. These abilities make them interesting for the screening purpose. Thus the aim of this project is to create a strain collection of yeasts from different habitats of a heavy metal contaminated site. The collected strains will be tested for their ability to produce plant growth promoting substances and will be used further for inoculation experiments with plants. Besides the proof of ability to promote plant growth the selected yeasts shall be used for phytoextraction experiments of heavy metals at field-scale.
 
 
Lembke, Christine

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ILRS Student

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Institute/Dep.
Friedrich Schiller University Jena
Institute for Inorganic and Analytical Chemistry
PhD Project:

Diatom pheromones – structure and function of communication mediators of unicellular algae

 
 
Institute/Dep.
University Hospital Jena
Clinic of Anaesthesiology and Intensive Care Medicine
Research Unit Experimental Anesthesiology
PhD Project:

Transcriptional profiling in human sepsis and identification of pathogenetic factors of multiple organ dysfunction

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Abstract: Sepsis results from the host response to infection. While a localized inflammatory host response is mandatory to control infection, its systemic progression is thought to promote...
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... multiple remote organ dysfunction and death. Thus, characterization of the factors that control progression and are associated with unfavourable outcome is a prerequisite to identify markers and targets for diagnosis and therapy. The analysis of this complex, partially redundant but also antagonistic pattern of transcriptional activation or suppression requires novel tools to assess a broad spectrum of interacting genes in a systems biology approach. Thus, the project aims in a translational manner to systematically study comparative transcriptomics of the progression from a localized infection to systemic sepsis in compartments reflecting the source, such as peritonitis and the target, such as kidney and lungs of systemic inflammation as they relate to changes in the transcriptome of circulating immune competent cells. This will allow identification and characterisation of factors that cause systemic inflammation, multiple organ failure and death. Methods of cellular and molecular biology, such as bead-chip array technology and silencing of differentially expressed transcripts associated with unfavourable outcome will be used to study their impact on the disease process and identify novel targets in a translational manner.
 
 
Lüdecke-Beyer, Claudia

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JSMC Fellow

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Institute/Dep.
Friedrich Schiller University Jena
Institute for Materials Science and Technology (IMT)
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Bio Pilot Plant
PhD Project:

Studying biofilm formation on biomaterials by a combined experimental and theoretical approach – a contribution to win the race for the surface

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Abstract: Background Bacterial infection in hospitals (nosocomial infection) is an increasing problem in general. It is estimated that about 800.000 cases of nosocomial infections occur in...
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... Germany per year. In the USA at least half of such infections are associated with medical devices as, for example, metallic implants in the human skeletal system. Such infections go along with biofilm formation. Bacterial communities of only one or of several species often form so-called biofilms, that is, aggregates of micro-organisms in which cells are stuck to each other and/or to a surface. More than 5 million central venous catheters (CVC) are inserted annually in the US. 2 – 12 % of CVCs insertions result in sepsis. Although the risk for infection concerning hip and knee prosthesis is low (1 – 3 %), the cost of management of a joint infection is estimated to exceed $50,000 per case. Bacteria exist in planktonic and sessile forms. Free floating planktonic bacteria can be attacked by the immune system as well as by antibiotics. However, after settling on a surface, the phenotype changes and an extracellular matrix is formed (e.g. from cellulose) protecting the cells. This results in significantly reduced susceptibility to antibiotics. Furthermore they face a locally weakened immune defense. Perfect hygiene assumed, bacteria may come from two types of sources. The first is the patient’s skin, the air or microbial contamination of the wound (e.g., in case of open fractures), the second is haematogenous or lymphatic seeding from infections somewhere else in the body. In a first step bacteria attach to the surface and start producing an extracellular matrix. When further bacteria have settled, the former change their phenotype and the biofilm is formed. Biofilm formation competes with tissue integration, since human cells, too, try to cover the implant material. Thus, the main goal after implantation is to avoid the formation of a microbial biofilm and promote tissue integration – the so called race for the surface. Despite the large complexity and variety of the parameters, the development of a biofilm can, in principle, be divided into six different stages: A) forming a conditioning film, for example adsorption of water and proteins in the blood stream; B) reversible and irreversible primary adhesion: the meeting between a conditioned surface and a planktonic microorganism. This stage is reversible and is dictated by a number of physicochemical variables, C) the anchoring or locking phase, which employs molecularly mediated binding between specific adhesins and the surface. The presence of one species of microorganism on a surface can promote the adhesion of another. The following stages D, E and F of biofilm formation are controlled by a variety of parameters which are independent of the substrate material. Various investigations were made to influence bacterial adhesion by materials surface proper¬ties, such as chemistry of surface, surface roughness, surface morphology or configuration and surface hydrophobicity or wettability. In general, microorganisms are less attracted by flat, smooth surfaces than by rough or porous surfaces. However, these studies are hard to compare since there are no standard tests for biofilm formation. All these studies are different in conditioning the surface, the type(s) of microbes used, the testing parameters and finally material properties such as "roughness" are not systematically changed. Besides the lack of standard tests for biofilm formation, there will be no opportunity in the near future for in-vitro tests of human cell adhesion and microbial biofilm formation at the same time. Actual test methods focus on in-vivo models. By computer simulation, the two processes could be brought together to analyse the competing process of tissue integration and biofilm formation. The long-term perspective is to substitute experiments with animals by computer simulations. Goal of the present project is to extract hard and weak effects from the high variety of material properties that might influence microbial adhesion. In biotechnology, biofilm reactors have long been commercially used in the treatment of wastewater and off-gas. Additionally, it becomes more and more evident that biofilm technology has an enormous potential in improving efficiency of converting lignocellulose materials to biofuels. Advantages of biofilms include concentration of cell-associated hydrolytic enzymes at the biofilm–substrate interface to increase reaction rates, a layered microbial structure in which multiple species may sequentially convert complex substrates, and fungal–bacterial symbioses that allow simultaneous enzymatic processes of different types. Of special importance in microbial communities is the effect of cheating: some cells cease secreting extracellular enzymes or substances to save metabolic costs, but benefit from the compounds secreted by cooperating cells. This usually impairs productivity.
 
 
Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Dept. Molecular and Applied Microbiology
University Hospital Jena
Clinic of Anaesthesiology and Intensive Care Medicine
Research Unit Experimental Anesthesiology
PhD Project:

Identification of protein antigens from Candida albicans for fungal sepsis diagnostics

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Abstract: Candida albicans is the most important fungal pathogen of nosocomial bloodstream infections (candidemia). Especially among immunocompromised individuals and patients in intensive care,...
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... C. albicans can cause invasive mycoses. Recently it has also been shown, that the late phases of bacterial sepsis is associated with a significant re-infection with opportunistic pathogenic fungi, particularly Candida albicans. Until now, the diagnosis of Candida infections remains difficult and the antifungal therapy is far from being efficient. In our proposed project, we aim at identifying immunodominant antigens of C. albicans from its secretome, which could bring to light novel diagnostic and prognostic biomarkers for systemic candidiasis, especially for its early infection phase. In a first approach, we have been analyzing the secretomes of Candida albicans through a combination of 2D-gel electrophoresis and MALDI-TOF-TOF-MS. This included the comparison of the secretome maps of the yeast form and hyphal form of Candida albicans. As second, we will characterise the IgM and IgG antibody response against C. albicans secreted proteins in a murine model of candidemia in comparison to control groups of uninfected mice. In parallel, serum samples from patients with fungal sepsis and from negative patient control groups will be collected at the Center for Sepsis Control and Care in Jena. They will allow us to compare the mouse immunoproteome data with sepsis patiant data in future. To detect immunoreactive proteins, our immunoproteomics approach will be coupled with bioinformatic analyses, especially cluster calculations and decision tree constructions.
 
 
Mac Nelly, Anita

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ILRS Student

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Institute/Dep.
Friedrich Schiller University Jena
Institute of Microbiology
General Microbiology and Microbial Genetics
PhD Project:

Expression control and biosynthesis of dehalogenating enzymes from anaerobic soil bacteria in response to the interaction with aerobic halogenating fungi

 
 
Maenz, Stefan

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Institute/Dep.
Friedrich Schiller University Jena
Institute for Materials Science and Technology (IMT)
PhD Project:

New resorbable calcium phosphate ceramic composites for the treatment of bone defects

 
 
Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Bio Pilot Plant
PhD Project:

Exploiting the metagenome of microbial communities on a microfluidic platform

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Abstract: In the course of this dissertation a surfactant-based microfluidic platform is employed to discover new bioactive natural products. Due to the failure of the recently predominant...
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... target-oriented screening approaches we intend to use a whole-cell-based screening method. To test for the synthesis of natural products within the droplets, we utilize reporter cells that ideally indicate antimicrobial activity, using constitutive or stress-inducible promoters. Three different strategies are envisaged. In one approach, we plan to exploit complex mixtures of antibiotic producers derived from different habitats like soil and sea water with laying the focus on yet uncultivated or slow growing actinomycetes. Second, the system can be applied in the research of silent gene clusters revealed by genome mining of characterized bacterial strains. This will be realized by cultivating a single strain of Actinobacteria under highly variable culture conditions implemented by media gradients during droplet generation. A third envisioned approach is to screen a combinatorial library of oligopeptides with putative antimicrobial activity (provided by Prof. Dr. Wiesmüller EMC microcollections GmbH, Tübingen). After detection of droplets with inhibited reporter strains the respective amino acid sequence can be elucidated by mass spectrometry analysis.
 
 
Märten, Arno

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JSMC Fellow

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Institute/Dep.
Friedrich Schiller University Jena
Institute of Geosciences
Applied Geology
PhD Project:

How do microbes influence the bioavailability of metals? A bioremediation study

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Abstract: This project aims at investigating the microbial impact on bioremediation of acidic, heavy metal contaminated and nutrient-deficient soils. Large areas within Europe are affected by...
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... former and actual mining activies often leading to metal contamination of surface water and groundwater. Since conventional clean-up technologies such as “dig and drop” are by far to expensive, cost-effective methods for remediation are needed. A promising and emerging technology for this is bioremediation, that is the use of plants and microbes for either extracting metals from the soil (phytoextraction) or stabilising them in the soil (phytostabilisation) to decrease mobility, bioavailability and therefore toxicity of the metals. Typically, fast-growing plants are used for bioremediation (then called phytroremediation) since they form high biomass and are therefore either able to extract large amount of metals or to protect soil from erosion and leaching of metals to groundwater. However, speciation, mobility and toxicity of metals are strongly influenced by microbial actions such as exudation of chelating agents, acidification, biomineralisation, biosorption, or uptake of metals. Thus, the focus of this project is on interaction of microbes with the environment by influencing speciation and by this bioavailability of metals. The research will be situated in the former Uranium mining area of Eastern Thuringia. Mining was terminated in 1990 and since then, billions of Euros were spent by the German Government for remediation of the area. In this area the Friedrich-Schiller university has established a test field site where phytoremediation is investigated at the field scale.” Microbes will be isolated from soil, from secondary minerals formed within the soils and directly from plant roots. They will be identified and characterized for their plant growth promoting properties and for their metal tolerance. Since it is well known that microbial communities perform different from the single strains alone, microbial communities will be identified that are promising to phytoremediation. To investigate how these microbial communities interact with their environment, experiments with shallow groundwater lysimeters will be set up. Lysimeters filled with homogenized contaminated substrate, planted with e.g. Festucra rubra (red fescue), Trifolium pretense (red clover) or Helianthus annuus (sunflower) and inoculated with promising microbial communities will be studied for plant performance. Redox potential, water tension, evaporation, soil water chemistry and the formation of secondary minerals will be monitored. To obtain a closer insight into the relevant processes, rare earth elements will be used as tracers to visualize processes such as dissolution, precipitation, sorption and uptake of metals in the system soil-water-biota. This project links Geology and Geochemistry with Microbiology. It is embedded in two large research groups (Georg Büchel/Dirk Merten, Applied Geology and Erika Kothe, Microbial Communication) with both groups already collaborating in various third-party funded projects.
 
 
Mattern, Derek

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JSMC Fellow

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Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Dept. Molecular and Applied Microbiology
PhD Project:

Metabolic Engineering and Bioprospecting of Secondary Metabolism in Filamentous Fungi

 
 
Meichsner, Doreen

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JSMC Fellow

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Institute/Dep.
Friedrich Schiller University Jena
Institute of General Botany and Plant Physiology
Dept. of Plant Physiology
PhD Project:

Symbiosis-specific exudate components from the beneficial root-colonizing fungus Piriformospora indica and Arabidopsis thaliana

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Abstract: In this project, we will study the beneficial interaction between the root-colonizing fungus Piriformospora indica and the model plant Arabidopsis thaliana. The endophytic fungus P....
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... indica colonizes of the roots of many plant species. Similar to arbuscular mycorrhizal fungi, P. indica promotes plant growth, biomass and seed production and confers resistance to biotic and abiotic stress (Shahollari et al., 2007, Vadassery et al., 2009, Camehl et al., 2011, Nongbri et al., 2012, and references therein). P. indica is a member of Sebacinales, grows inter - and intracellularly and forms pear shaped spores, which accumulate within the roots and on the root surface. After the establishment of a beneficial interaction, barely any defense or stress genes are activated and no reactive oxygen species are produced by the host against P. indica (Camehl et al., 2011). The endophyte releases a small compound into the medium/rhizosphere which induces root-specific [Ca2+]cyt elevation in Arabidopsis and N. tabacum. [Ca2+]cyt elevation is followed by a nuclear Ca2+ response (Vadassery et al., 2009), similar to signalling events in arbuscular mycorrhizal fungi.
Using established cultivation and co-cultivation conditions, we will try to identify proteins, peptides and other biomolecules which are released from the two partners into the medium. Comparative analyses of the secretomes and metabolomes (released by the microbial and plant partners alone and in symbiotic interaction between the two partners) should identify those compounds which are symbiosis-specific. Since the genomes of both organisms are sequenced and available, the origin of the proteins and peptides can be identified. Furthermore, genome mining should help to identify the origin and biosynthesis of the symbiosis-specific biomolecules.
 
 
Meinel, Christian

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JSMC Fellow

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Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Junior Research Group
Chemistry of Microbial Communication
PhD Project:

Immunevasion of the Gram positive bacterium Streptococcus pneumoniae

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Abstract: S. pneumoniae is a Gram positive bacterium, which can asymptomatically exist in the upper respiratory tract of healthy individuals. However, S. pneumoniae can also cause severe and life...
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... threatening diseases, including pneumonia, meningitis, sepsis and also hemolytic uremic syndrome (HUS). Especially children, immunocompromised persons and older individuals are at risk for an invasive S. pneumoniae disease 1. Upon infection S. pneumoniae is challenged by the complement system, a part of the human innate immune response. In order to persist and to establish pathogenesis this bacterium has to evade the complement attack of the human host. To this end, S. pneumoniae has evolved several efficient strategies to evade the human innate immune response. One complement evasion strategy that is used by S. pneumonia and other pathogenic microbes is the recruitment and exploitation of human complement regulators to disturb complement activity 2. The pneumococcal surface protein C (PspC) and the translation elongation factor Tu (Tuf) are two surface expressed virulence proteins of S. pneumoniae, which support the immune evasion of this bacterium e.g. by recruiting human complement regulators to the pneumococcal surface 3,4. Until now, the various features by which these bacterial immune evasion proteins contribute to the pathogenesis of S. pneumoniae are only rudimentarily understood. Therefore, the aim of this project is to elucidate the exact mechanisms how PspC and Tuf contribute to the immune evasion of S. pneumoniae and how they support pathogenicity in life threatening diseases.
 
 
Menezes, Riya

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JSMC Fellow

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Institute/Dep.
Leibniz Institute of Photonic Technology (IPHT)
Dep. Spectroscopy/Imaging
PhD Project:

Analysis of nuclear migration in Schizophyllum commune by high resolution by in vivo microscopy/spectroscopy

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Abstract: Nuclar distribution, localization and migration in fungi is necessary for polar growth, branching, and sexual development in fungi. The full genome sequence of the model basidiomycete...
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... Schizophyllum commune allow the identification of genes involved in this process, both with intracellular signal transduction and nuclear positioning by genetic manipulation and phenotypic characterization. We could already show involvement of Ras in signal transduction, and we have identified and deleted genes encoding dyneine heavy chain. Additionally, we established methods to loclaize proteins in wildtype and mutant strains by immunofluorescence microscopy, including cytoskeleton stainings. In vivo studies with real-time, high-resolution microscopy should be applied within the frame of this PhD project to determine the precise co-localization of proteins involved in the rapid nuclar migration processes typically associated with mating interactions in higher basidioymcetes. The aim of the project is to provide the experimental basis for a modular enhancement of the rapid fluorescence wide field microscopy in the sub-100nm range. This, together with a Raman-based image contrast, should pave the way for an improved multicontrast microscopy technology. Within the PhD project, this technology will implemented and further developed for the online analysis of growth processes in homobasidomycetes. Moreover, microspectroscopic approaches that allow for a combination of rapid fluorescence nanometer resolution microscopy with resonance spectroscopic contrast will be developed.
 
 
Merker, Holger

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JSMC Fellow

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Institute/Dep.
Max Planck Institute for Chemical Ecology
Dept. of Bioorganic Chemistry
PhD Project:

Chemical ecology and coevolution of bacterial consortia

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Abstract: Interactions between microbial species, such as competition and cooperation, influence the abundance and distribution of the respective species. Metabolic cooperation among multiple...
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... bacterial species for example plays a key role in shaping and maintaining microbial consortia. This study aims at identifying the ecological selection pressures that govern the coevolution of two coexisting bacterial species as well as unravelling the mechanisms responsible for stabilising these communities. To this end, different pairwise combinations of soil-borne bacterial species will be co-cultured and the structural basis of the resulting ecological interaction characterized by using methods of analytical chemistry. In long-term experiments, in which two interacting partners are exposed to different ecological environments, both species are not only expected to adapt to each other but also the quality of the ecological interaction is likely to change (e.g. from neutral to cooperative, or from cooperative to exploitative), depending on the ecological environment the interaction has experienced. Detailed genetic, chemical and microbiological analyses of the ancestral and the derived consortia will be performed to identify qualitative and quantitative changes of the interspecific interactions as well as the causal evolutionary forces.
 
 
Mhatre, Eisha

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JSMC Fellow

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Institute/Dep.
Friedrich Schiller University Jena
Institute of Microbiology
Junior Research Group Terrestrial Biofilms
PhD Project:

Phenotypic heterogeneity in bacterial biofilms

 
 
Mori, Jiro

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GRK1257 Student

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Institute/Dep.
Friedrich Schiller University Jena
Institute of Ecology
Dep. Aquatic Geomicrobiology
PhD Project:

Unique algae bacteria mineral assemblages in highly metal-contaminated stream

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Abstract: Highly metal-contaminated, slightly acidic (~pH 6.0) underground water emerges in a former uranium mining district (Ronneburg, Germany). Recently, massive upweJling formed sm all...
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... streams and iron-rich terraces along grassland down to the drainage creek. These streams are characterized by conspicuous greenish and brownish algae (streamers) during the summer months that show iran incrustations. Since these streamers have not been characterized, the aim of the study is to elucidate (a) if the algal streamers are colonized by microorganisms that might be involved in iran oxidation, (b) the spatial arrangement of microbial constituents, and (c) the type of iran minerals and their location in the streamers, Observation of streamers with ClSM and SEM revealed that streamer-forming filamentous microalgae are encrusted with iron mineral precipitates that are coJonized by bacteria, Mineral precipitates are distributed in a regular but discontinuous pattern on the algal filaments, Moreover, EP5-like polysaccharides were observed on the minerals, Chemical analyzes (FTIR, ICP-MS, and Raman spectroscopy) of the mineral precipitates revealed that ferrihydrite was the major constituent of the mineral fraction, Microbial community structures of the streamers were analyzed by amplicon pyrosequencing targeting 165 rRNA genes with bacterial primers. Abundances were quantified by qPCR assays employing primers specific for different groups of iron oxidizing bacteria. Results indicated that Gallionella-related iron-oxidizing bacteria were the most abundant Bacteria. They were not only attached to the surface of algal filaments but were also metabolically active in streamer communities. Gallionella seem to preferably colonize algal filaments and cause formation of ferrihydrite. The site-specific colonization of Gallionella and accumulation of ferrihydrite likely were induced by the algal physiological activity and its morphoJogy.
 
 
Mrozinska, Anna

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IMPRS Student

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Institute/Dep.
Friedrich Schiller University Jena
Institute of General Botany and Plant Physiology
Dept. of Plant Physiology
PhD Project:

Molecular analysis of the interaction between Arabidopsis thaliana and Piriformosphora indica

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Abstract: The goal of my PhD project is the analysis of a newly discovered signaling cascade for the beneficial interaction between root-colonizing endophytes and plants. For this, a...
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... well-established model system Piriformospora indica/Arabdiopsis thaliana is used. The endophyte colonizes the roots of many plant species and promotes their growth and performance. For establishing the interaction, the second messanger phosphatidic acid, phospholipases, the protein kinase PDK1 and the AGC kinases OXI1 and AGC2-2 are nesessary. I will focus on the role of phospholipases and the AGC kinases in this symbiosis. I am also interested in the role of chitin and other small signaling compounds that are secreted by the fungus and recognized by the plant. For all this I am using a physiological and molecular approach.
 
 
Narvekar, Sneha

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GRK1257 Student

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Institute/Dep.
Friedrich Schiller University Jena
Institute of Geosciences
Chair for Hydrogeology
PhD Project:

Bioconversion of mobile organo-mineral geosorbents: microbial effects on reactivity and mobility

 
 
Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Dept. Molecular and Applied Microbiology
PhD Project:

Inducing the formation of fungal secondary metabolites by the interaction with Streptomyces

 
 
Novohradská, Silvia

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JSMC Fellow

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Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Dept. Molecular and Applied Microbiology
PhD Project:

Soil amoeba interactions with filamentous fungi as driving forces for pathogenicity

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Abstract: The filamentous fungus Aspergillus fumigatus is a well described example of an environmentally acquired pathogen. The colonization of the host organism is based on the multifactorial...
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... virulence mechanisms, which may have emerged long before the appearance of innate immune systems and could at least partially result from the selection pressure imposed by amoeba predation (Seaton and Robertson, 1989; Casadevall, 2012). Our central question is therefore how the interaction with predatory amoeba could also have stimulated the development of virulence mechanisms? Where did the fungus "learn" to cope with the residual innate immune responses and has acquired the abilities necessary for an invasive host colonization? Why some fungi use such highly structured mycotoxins which seem to target a wide range of cellular process in vertebrates? References Seaton A, Robertson MD (1989) Aspergillus, asthma, and amoebae. Lancet 1:893-4. Casadevall A (2012) Amoeba provide insight into the origin of virulence in pathogenic fungi. Adv Exp Med Biol 710:1-10
 
 
Novoselov, Alexey

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JSMC Fellow

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Institute/Dep.
Max Planck Institute for Chemical Ecology
Dept. of Bioorganic Chemistry
PhD Project:

Impact of plant toxins on the gut microbiota community of Lepidoptera

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Abstract: Gut microbial communities are significantly different from the environmental microbial community. Recent metagenomic studies demonstrated that closely related insects had a more similar...
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... gut microbial community. In Spodoptera littoralis larvae exists a core microbiome, but the microbial composition can be altered by the ingested diet. Under reproducible laboratory conditions larvae of S. littoralis and Helicoverpa armigera developed largely the same, almost static community. To analyze the food derived factors that control the composition of a microbial gut community, we tested typical plant toxins as admixtures in an constant artificial diet. Toxins were added to an artificial diet as admixtures in natural concentrations (typical concentrations that occur in plants). The body weight, length and survival of the larvae were determined as fitness parameters. It was shown that plant toxins: 3-nitropropionic acid (3-NPA), amygdalin, crotalin, coumarin, 8-methoxypsoralen slows down the growth of larvae of Spodoptera littoralis larvae. The 3-NPA (0.05%) and coumarin (0,1%) was selected for further processing. At the different time points the composition of the gut communities was documented by 454-sequencing. After the feeding on toxic diet 663 bacterial phylotypes were found. The significant changes of the communities were shown to depend on the applied toxins. Firmicutes and Proteobacteria were the two most diverse phyla of bacteria in the untreated gut microbial community. On diet with toxins the diversity of Proteobacteria in Spodoptera littoralis gut bacterial community decreased. Firmicutes were present in all samples. After applications of toxins microbial diversity strongly decreased, up to 95% of OTUs can be classified as Firmicutes. In the core microbial community Enterococacea was the largest group, Enterococus mundtti was highly abundant in the gut and resistant to applied toxins. Application of ampicillin and tetracycline to artificial diet lead to a deletion in development of S. littoralis larvae also the abundance of Enterococus mundtti significantly decreased. The gut microbial community is sensitive to the applied toxins and accelerates the growth of larvae on the artificial diet.
 
 
Oago Onchuru, Thomas

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JSMC Fellow

Email »

Institute/Dep.
Max Planck Institute for Chemical Ecology
Research Group Insect Symbiosis
PhD Project:

Host and symbiont contributions towards parasite resistance in cotton stainer bugs

 
 
Otzen, Christian

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publications »

JSMC Fellow

Email »

Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Research Group
Microbial Immunology
PhD Project:

Interaction of Candida albicans and host cells: Fungal nutrient acquisition and host defense mechanisms

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Abstract: Candida albicans is the most important fungal pathogen in noscomial infections. Although the pathobiology of C. albicans has been studied since many years, hardly anything is known...
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... about the nutrient acquisition from the host and the underlying physiology of the fungal cells. Isocitrate lyase, a key enzyme of the glyoxylate cycle, has been shown to be upregulated during host/pathogen interaction, but, although mutant strains displayed a reduced virulence, the impact of the glyoxylate cycle in nutrient acquisition is still a matter of debate. Besides carbon also nitrogen sources have to be aquired, which can be provided from protein degradation. This is supported by the essential role of secreted aspartic proteases in pathogenesis of C. albicans. Nevertheless, the degradation isoleucine, valine and methionine leads to the toxic intermediate propionyl-CoA. For A. fumigatus it has been shown that the methylcitrate cycle is essential for removal of propionyl-CoA and a deletion mutant of the key enzyme methylcitrate cycle, which is unable to remove propionyl-CoA, is strongly attenuated in virulence. Since the C. albicans genome does not contain genes of the methylcitrate cycle and also does not posses the coenzyme B12-dependent methylmalonyl-CoA pathway, an alternative metabolic pathway for the removal of toxic propionyl-CoA has to exist. The aim of this study is the identification and purification of the enzymes involved in propionyl-CoA degradation and the elucidation of their relevance in the interaction between the pathogen and the host. The impact on pathogenesis will be studied in different infection models after the construction of specific deletion mutants.
 
 
Pähtz, Vera

publications »

Email »

Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Dept. Molecular and Applied Microbiology
PhD Project:

The hypoxic response in the pathogenic mold Aspergillus fumigatus and its relevance to disease

 
 
Pande, Samay

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publications »

JSMC Fellow

Email »

Institute/Dep.
Max Planck Institute for Chemical Ecology
Dept. of Bioorganic Chemistry
Experimental Ecology and Evolution
PhD Project:

Ecological mechanisms that determine the maintenance of cooperative interactions

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Abstract: Mutualisms are interspecific interactions, in which both partners derive a fitness benefit. Although mutualisms are ubiquitous and of profound ecological importance, their evolutionary...
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... stability is difficult to reconcile with natural selection: conflicts of interest are expected to arise whenever organisms direct benefits to non-relatives at their own cost. Such conflicts are predicted to lead to the evolution of cheating types that reap mutualistic benefits without bearing the costs of the cooperation, which ultimately should collapse the interaction. The aim of this project is to identify those ecological conditions that can limit selection for cheating and hence stabilize mutualistic interactions. To this end, we will design and genetically engineer synthetic mutualistic interactions between two bacterial species. In long-term evolution experiments, we will expose the resulting interactions to different selection regimes that are predicted by evolutionary theory to contribute to the maintenance of mutualistic interactions. Depending on the selective regime and the cost-to-benefit ratio of the cooperation for the employed strains, we expect some conditions to collapse the interaction, while others should be able to support it. Since the arisal of cheating types is expected to be the main evolutionary force leading to instability by eroding the mutualistic interaction, identifying ecological factors that favour/ hamper the evolution of cheating types as well as studying the evolutionary consequences of cheaters arising, will be central to this project. The experimental work will be guided by theoretical models developed in the group of Prof. Dr. Stefan Schuster (Department of Bioinformatics, FSU Jena) as well as supported by the expertise of Dr. Uwe Horn’s laboratory (Hans Knöll Institute) on the long-term operation of chemostat cultures.
 
 
Park, Hea-Reung

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publications »

JSMC Fellow

Email »

Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute and Friedrich Schiller University Jena
Jena Microbial Resource Collection (JMRC)
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Dept. Molecular and Applied Microbiology
PhD Project:

Survival strategies of humanpathogenic zygomycetes inside macrophages

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Abstract: Zygomycetes are associated with plants, fungi, animals and humans. While the interaction with plants, fungi and arthropod animals is mainly harmless or even beneficial (due to...
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... mutualistic relationships), the liaison with humans is highly invasive leading to rapid death of patients. Pathogenesis is facilitated in these interactions by a hit and run strategy of the pathogen followed by purging of deleterious properties which become virulence factors, amongst many others the mode of interaction with human macrophages. To monitor the interplay between hosts and zygomycetous pathogens at the cellular level, two different murine cell lines of macrophages (phagocytizing J774.A1 cells and a specific line originating from lung) will be infected with spores from zygomycetes reported to date as human pathogens (approx. 28 species) and investigated with confocal laser scanning microscopy. In parallel the zygomycetes will be subjected to amoebae (Dictyostelium discoideum and Entamoeba coli) to test the hypothesis that the survival strategies for soil-borne, potentially human pathogenic fungi after ingestion by macrophages and amoebae are similar. The PhD student will mainly work in the Jena Microbial Resource Center (JMRC) at the Leibniz Institute for Natural Product Research and Infection Biology – Hans Knöll Institute (HKI). On macrophage assays we will cooperate with Prof. A. Brakhage (HKI) and on immunological problems, we will cooperate with Prof. P. Zipfel (HKI). In cooperation with the lab of Prof. Schuster the parameters derived from fungus-macrophage/amoebae interactions will be modeled by systembiological (game theoretical) approaches (see JSMC Project No: 65/2012 A Systems Biology approach to studying zygomycoses).
 
 
Phieler, René

publications »

GRK1257 Student

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Institute/Dep.
Friedrich Schiller University Jena
Institute of Microbiology
Microbial Communication
PhD Project:

Microbially supported phytoremediation of the heavy metal contaminated site Gessenwiese

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Abstract: The increasing release of heavy metals to the environment due to anthropogenic activities such as mining operations and smeltering is a serious problem world-wide. Microbially...
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... supported phytoremediation may be viewed as potentially useful approach. Soil bacteria and mycorrhizal fungi can alter physico-chemical properties in the rhizosphere and may alter soil metal bioavailability for uptake into plants. This project will focus on studying remediation potential of selected plants at the heavy metal contaminated site Gessenwiese, located on the basement of the former uranium leaching heap Gessenhalde near Ronneburg, Thuringia. The objective is to develop more knowledge-driven field remediation techniques to remediate and restore contaminated sites. Of special interests are the interactions between soil microorganisms and plants with respect to the uptake of heavy metals. Field experiments as well as pot experiments will be carried out in order to assess the effects of microbial inoculation on biomass production and total uptake of heavy metals by host plants.
 
 
Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Dept. Microbial Pathogenicity Mechanisms
PhD Project:

The role of morphology for fungal pathogenicity

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Abstract: The pathogenic fungus Candida albicans is able to colonize many different body sites and infections range from harmless superficial lesions up to severe and life threatening...
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... disseminated candidiasis. For the invasion and tissue penetration process of the fungus the transition from the spherical yeast to the filamentous hyphal growth form is essential. In addition to adhesion and invasion hyphae also mediate the escape from host cells such as endothelial cells and macrophages after internalization. Since the yeast-to-hypha transition is of great importance for the development of disease it is not surprising that this process is tightly regulated by a complex network of both positive and negative regulatory factors. While the knowledge about regulatory mechanisms controlling morphogenesis is rising, the exact role of morphology for the pathogenicity of C. albicans is still not fully clear. Studies revealed that not all filament-deficient mutants are attenuated in virulence, indicating a more complex relationship between morphology and infection process. Therefore the aim of this project is to analyze the contribution of different regulators of filamentation to pathogenesis and host-pathogen interaction. To analyze these regulators in a comparable genetic background, strains carrying the gene of interest under a doxycycline-inducible promoter will be constructed. These strains will then be analyzed in detail for filamentation defects, expression of virulence-associated factors and interaction with different host cells in vitro. Furthermore, different in vivo models will be used to determine the impact of the genes of interest on the various aspects of the host-pathogen interaction in complex systems.
 
 
Pollmächer, Johannes

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publications »

JSMC Fellow

Email »

Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Research Group Applied Systems Biology
Research Group: Systems Biology / Bioinformatics
PhD Project:

Development of a multi-scale simulator to model host-pathogen interactions

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Abstract: The host response against invading pathogens involves both innate and adaptive immunity and represents the concerted action of a multitude of different signaling molecules and immune...
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... cells. Complexity arises due to the fact that the individual constituents of the immune system have characteristic properties, for example, with regard to their mode of migration and to their interaction with the pathogen and with other constituents. In addition, these properties may change in the course of time implying that the dynamic regulation of the immune response spans different time- and length-scales. The objective of this project is to set up a flexible and extensible computational framework that can be generally applied to simulate aspects of immune responses at the multi-cellular level. This challenging and computationally demanding task is tackled within a hybrid agent-based modeling approach. In this approach, which has proven to be successful in previous studies [1-4], the dynamics of cells is represented by discrete agents that migrate and interact in a continuous spatial environment. The dynamics of the environment is represented by differential equations for the extracellular molecular concentrations that may be influenced by and impact on the agent dynamics. The dynamics of internal agent properties may as well be represented by individual systems of differential equations for the intracellular molecular network or may be represented by a set of rules, depending on the available experimental data basis. The structure of the computational framework includes five modules: (i) Data Input: This module allows for the flexible input of simulation data and must be user-friendly and open for the unique combination of very different experimental data bases. For example, parameters of the migration and interaction behavior may be obtained from the analysis of microscopy data while the time-dependent cellular state may be determined from kinetic data on the intracellular molecular network. (ii) System Simulation: In this module the actual simulation is performed within the hybrid agent-based model approach. It has to be programmed in an object-oriented manner and should be optimized for simulating multi-cellular systems in a continuous space representation of the three-dimensional environment. This may involve the use of neighbor-list methods and/or parallelization techniques in view of the required computational resources in terms of computing time and memory. (iii) Data Output: The output data of the computer simulations are stored in a well-organized fashion that allows for the fast identification of the relevant readouts for comparison with experiment. (iv) Data Analysis: For comparison with experimental readout further analysis of the output data may be required that is performed within this module. (v) Data Visualization: System configurations are visualized and the individual frames of the simulation are combined into movies to allow for the comprehensive presentation of results. The computational framework is to be written in the object-oriented programming language C++ under Linux and the development of the simulator is to be documented in a detailed record. The goal of this more technical project is to provide a reliable and flexible tool that can be applied to various biological systems, depending on the available experimental data basis and present scientifically interesting issues. Examples for applications of the multi-scale simulator to aspects of innate and adaptive immunity include, but are not restricted to, (i) regulation of neutrophil extracellular traps (NETs) in response to pathogen invasion, (ii) phagocytosis of fungal spores by macrophages, (iii) phases of T cell activation in lymph nodes.
 
 
Preußger, Daniel

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publications »

JSMC Fellow

Email »

Institute/Dep.
Max Planck Institute for Chemical Ecology
Dept. of Bioorganic Chemistry
PhD Project:

The evolution of metabolic cooperation within bacterial communities: causes and consequences

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Abstract: Bacteria live in diverse communities and frequently interact by the exchange of metabolites. However, those cooperative interactions pose a conundrum to evolutionary biology: costly...
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... benefits directed to other cooperating individuals are vulnerable to be undermined by selfish mutants, which gain a selective advantage by not reciprocating. Despite this seeming conflict, cooperation within and between different bacterial species is very common and plays a vital role in many ecosystems. Therefore, conditions, promoting the evolution and maintenance of such interactions, are worthwhile to be investigated: These are in detail ecological factors, co-evolutionary trajectories and consequences of metabolic capabilities within interacting species. To study effects of these parameters, long-term coevolution experiments will be performed under varying ecological conditions. Precisely defined bacterial consortia are allowed to develop metabolic cooperation, initially starting from a synthetically engineered obligate by-product interaction based on amino acid auxotrophies. A well-established analysis pipeline, in which the derived consortia are analysed for genetic and phenotypic changes that occurred during the selection experiments, will then help to causally link different initial conditions to the observed evolutionary outcomes. Evolved cooperation will be characterised by analysing fitness relative to ancestors, local adaptation, and frequency dependent selection of partners. In this way, several hypotheses on the causes and consequences of metabolic cooperation within bacterial communities can be scrutinized.
 
 
Ramachandra, Shruthi

publications »

ILRS Student

Email »

Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Dept. Microbial Pathogenicity Mechanisms
PhD Project:

Host pathogen interactions of human-pathogenic yeast

 
 
Raszkowski, Daniel

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publications »

JSMC Fellow

Email »

Institute/Dep.
Friedrich Schiller University Jena
Institute of Pharmacy
Pharmaceutical Biology I
PhD Project:

Evolution of glorin-based intercellular communication in social amoebae

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Abstract: The “social amoebae” are a group of unicellular organisms that transiently achieve multicellularity by aggregation of single cells, aimed at the formation of fruiting bodies whose...
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... spores survive environmental conditions unfavorable for growth. Multicellular development of social amoebae is accompanied by intensive intercellular communication, which has to some extent interesting parallels with bacterial quorum-sensing and quorum-quenching systems. Extracellular signaling molecules used by social amoebae to coordinate aggregation of usually reffered to “acrasins” irrespective of their chemical natures. A hallmark or amoebal acrasin systems is that the signaling molecule is periodically degraded, which allows the amoebae to position in an acrasin gradient and move to the highest concentration of the signaling molecule, which is the aggregation center. Thus, besides the signaling molecule and its receptor, an acrasin system of social amoebae requires a self-produced and secreted enzyme that inactivates the acrasin. Several of the species that diverged late in the evolution of social amoebae use cAMP to regulate aggregation. In this project we follow the hypothesis, based on our previous work, that the phylogenetically oldest species of social amoebae use the modified dipeptide glorin instead of cAMP as the intercellular signaling molecule that coordinates aggregation. In addition, we assume that glorin is secreted by cells of genus Polysphondylium and that these species produce an enzyme (a “glorinase”) that is capable of inactivating glorin in the extracellular space. A major goal of this project is to identify the glorinase-encoding gene from Polysphondylium pallidum. To this end, we will establish a biochemical assay to measure glorinase activity in the buffer supernatant of aggregating P. pallidum cells. This assay will be fundamental to purify extracellular glorinase from aggregating P. pallidum cells by activity-guided fractionation. The glorinase protein will be identified by means of proteomic methods and this information will be used to identify the glorinase gene in the P. pallidum reference genome. To explore the function of glorinase in coordinating P. pallidum aggregation, we will generate a knock-out mutant of glorinase in P. pallidum. This mutant will be characterized in terms of developmental phenotypes. A detailed expression of the glorinase gene will answer the question how the gene is regulated at the transition from growth to development of P. pallidum cells. Search for functional glorinase orthologs in other sequenced genomes of social amoebae will shed light on the evolution of the glorin-based communication system in social amoebae as well as on the origin of ths system and its relation to bacterial quorum-sensing systems.
 
 
Reinicke, Martin

publications »

GRK1257 Student

Email »

Institute/Dep.
Friedrich Schiller University Jena
Institute of Microbiology
Microbial Communication
PhD Project:

Identification of microbial consortia in heavy metal polluted soils

 
 
Richter, Jessica

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publications »

JSMC Fellow

Email »

Institute/Dep.
Friedrich Schiller University Jena
Institute of German Linguistics
PhD Project:

Multiphoton nano markers

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Abstract: Optical microscopy has been one of the most important tools in biology for almost a century. Recently fluorescence imaging has revolutionized the field, providing images with superior...
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... contrast and resolution as also recognized by the 2008 Nobel Prize committee1. With this work, we propose to use a new type of nanomaterials with outstanding optical properties for enlarging the imaging and sensing tool-box. These nanomaterials, either particles or wires made of a special kind of niobate crystals, emit light through the second-harmonic generation (SHG) mechanism rather than fluorescence. Compared to conventional fluorescent markers such as organic dyes, green fluorescent proteins (GFPs) or quantum dots, they possess several key advantages, including long-term observation without photobleaching, flexibility in excitation wavelength, coherent signals for three-dimensional imaging, narrow signal bandwidth for greater noise rejection, ultrafast response time, and excellent biocompatibility. Moreover, they also possess electro-optic properties useful to move and orient biological objects or to heat the surrounding medium if coupled to plasmonic effects. The challenge of this proposal is to bridge the gap between physics and biology by studying the fundamental physical properties of this novel type of nanoparticles, and subsequently by using them as markers in biological applications or as local light or field emitters in optofluidic chips. Different multidisciplinary solutions at the boarder of optics, biochemistry and biology will be studied such as biochemical functionalization, optical or electrical tweezing, and lithography methods.
 
 
Rischer, Maja

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publications »

ILRS Student

Email »

Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Junior Research Group
Chemical Biology of Microbe-Host Interactions Leibniz Institute for Natural Product Research and Infection Biology
PhD Project:

Exploring the chemical potential and mechanisms of marine microbe-invertebrate interactions

 
 
Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Research Group
Microbial Immunology
PhD Project:

Host-pathogen interactions during Candida albicans translocation through the gut

 
 
Saraiva, João

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publications »

JSMC Fellow

Email »

Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Research Group:
Infection Biology
PhD Project:

Exploring unbound human and mouse inflammatory defense mechanisms against bacterial and fungal infection employing bioinformatics/systems biology concepts

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Abstract: Systemic infection of the human host can arise from pathogenic bacteria such as Staphylococcus aureus and non-pathogenic bacteria such a E. coli, but also from overall abundant fungal...
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... species such as Candida albicans. Such infections can lead to an unbound inflammatory response of the human host and finally sepsis. Sepsis is one of the leading causes of death world wide. Besides this, the Systemic Inflammatory Response Syndrome (SIRS) can arise from injury without an infectional cause. SIRS comes also along with unbound inflammation. It has similar clinical symptoms at time of diagnosis but the patients show a much better recovery in comparison to sepsis. Inflammation caused by fungi and bacteria seem to utilize different signaling pathways. The aim of the project is to - explore signaling and metabolic networks in the immune cells to enroll similarities and differences between these diseases (bacterial and fungal caused inflammation, SIRS), - put up mathematical models for the different causes of inflammation (fungal, bacterial, SIRS) which explain the different regulatory response, and to use these models i) for predicting the cause of the disease, ii) to elucidate the difference in cellular regulation between the different microbial and non-microbial caused dis-regulations and to get an insight into the communication between immune cells and the parasitic microbes, and iii) to identify targets for switching back the immune cells from a pathogenic back to a normal like behavior, i.e from unbound to controlled inflammation.
 
 
Institute/Dep.
University Hospital Jena
Clinic of Anaesthesiology and Intensive Care Medicine
Research Unit Experimental Anesthesiology
PhD Project:

Effects of hypoxia and intestinal nutrients on intestinal barrier function and translocation of microorganisms

Abstract: The transition of C. albicans from a commensal within the gut to an invasive pathogen is of great clinical importance. However, it is largely unknown which host factors trigger the...
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... transition and which fungal factors are essential for translocation through the gut. There is experimental evidence that intestinal ischemia/hypoxia, e.g., during major surgery and shock/sepsis, weakens the intestinal barrier and may promote translocation of C. albicans. We furthermore hypothesise that the environmental alterations during intestinal hypoxia trigger a specific fungal response that is associated with increased translocation. The aim of this project is to dissect the translocation process with regard to the involved anatomical sites and host cells, immune response and fungal factors. Furthermore, the effect of intestinal ischemia/hypoxia on C. albicans translocation will be evaluated. In vitro cell culture experiments will be used to determine intestinal cell barrier functions under different levels of hypoxia and the consequences for interaction with C. albicans. Transcriptional analysis will be used to identify pathways involved in epithelial response to hypoxia and fungal factors contributing to the interaction. The obtained results will be confirmed in murine ex vivo and in vivo models. To determine at which anatomical sites translocation occurs and which host cells are involved, a murine in vivo model of dissemination from the gut will be established and analysed by using fungal reporter strains and imaging (IVIS), determination of fungal burden, histology and immunhistochemistry, FACS and cytokine ELISAs. To test the hypothesis that intestinal ischemia/hypoxia enhances translocation of C. albicans through the gut, the consequences of intestinal hypoperfusion on the colonisation and translocation of C. albicans will be tested in an ex vivo model using externally perfused gut and in vivo. Transcriptional analyses as well as loss-of-function models of both host and fungus will be used to identify factors involved in the translocation process under normoxia and hypoxia in vivo. Furthermore, the transcriptional analyses allow determine whether intestinal ischemia/hypoxia leads to a specific fungal response involved in translocation. Finally, based on the transcriptome analysis and on barcoded mutant libraries, C. albicans mutants will be tested for their translocation potential to identify fungal factors essential for translocation.
 
 
Schmalwasser, Andreas

publications »

IMPRS Student

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Institute/Dep.
Friedrich Schiller University Jena
Institute of Geosciences
Chair for Hydrogeology
PhD Project:

MOPS in the critical zone – the neglected mobile pool of soil organic matter

 
 
Schmidt, Hella

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publications »

JSMC Fellow

Email »

Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Dept. Molecular and Applied Microbiology
PhD Project:

Interactions of the fungal pathogen Aspergillus fumigatus with human macrophages

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Abstract: Aspergillus fumigatus is the most important airborne human pathogenic fungus. It causes severe diseases with high mortality rates, particularly in immunocompromised patients. In the...
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... lung, alveolar macrophages represent the first line of defense against inhaled conidia. Effective elimination of the fungus requires phagocytosis and the localization of conidia in acidified phagolysosomes. However, A. fumigatus is able to interfere and manipulate the formation of a functional phagolysosome. Engulfed conidia block the acidification of the phagolysosome of the host macrophage and thereby evade their intracellular killing. Previous studies revealed that the conidial pigment, the dihydroxynalphthalene (DHN)-melanin, plays a decisive role in this survival strategy. We hypothesise that certain components of the phagosomal membrane are targeted by DHN-melanin to prevent the phagolysosomal maturation. A protocol for the isolation of conidia-containing phagolysosomes is applied to analyse proteins of the phagolysosome in order to identify potential receptors or effectors involved in the process of phagosomal maturation. By using immunofluorescence and confocal microscopy, the contribution of selected receptors to maturation of the phagolysosome is monitored. The approaches will help to elucidate the yet unknown mechanism of how A. fumigatus conidia evade their intracellular killing and disseminate in the human host.
 
 
Schoeler, Hanno

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publications »

JSMC Fellow

Email »

Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Dept. Molecular and Applied Microbiology
PhD Project:

Imaging und Proteomanalyse der Interaktion von Aspergillus fumigatus mit Neutrophilen Granulozyten

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Abstract: Aspergillus fumigatus is the most important air-borne human-pathogenic fungus. This opportunistic pathogen can cause invasive aspergillosis in immunosuppressed patients (e.g. organ...
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... recipients or patients with CGD). The PhD-project aimes to analyse the interaction between the neutrophil granulocytes and the fungus. It is on the one hand of interest to highlight the role of the DNases that are secreted by the fungus. On the other hand the project should elucidate the host defense-strategies upon confrontation with Aspergillus fumigatus, especially the formation of neutrophil extracellular traps (NETs) - DNA-fibers suspected to inhibit fungal growth and to mark it for the immune system. The latter process could serve for recognition of the fungus by the immune cells which will be investigated with a confocal laser-scanning microscope. Within an interdisciplinary framework the time-laps movies will then be analysed in-silico by the bioinformatic department of the HKI. In another collaboration with the Universitätsklinikum Würzburg an analysis of differences in NET-formation is planned. Here, the influence of selected genetic diseases, resulting in impaired neutrophil activity, will be investigated in more detail. Previously, the transcriptome of neutrophil granulocytes was studied. For this project the next step will be performed by generating the proteomic map of the neutrophil granulocytes during infection. The project highlights the interactions between neutrophil Granulocytes and the human-pathogenic fungus Aspergillus fumigatus. This includes also all kinds of communication between them. There are distinct signs for the immune system that a pathogen is present which lead to subsequent activation of the immune reaction, for example the NET formation. But there are also signals for the pathogen about the hostile environment it is colonizing which leads to avoidance strategies. Therefore, investigation of the complex interplay between the host and the fungus will not only contribute to the understanding of infection by Aspergillus fumigatus but might also serve as a model for immune defense mechanisms towards other fungal pathogens.
 
 
Schulze, Robert

publications »

Email »

Institute/Dep.
Friedrich Schiller University Jena
Institute for Materials Science and Technology (IMT)
PhD Project:

New strategies for the creation of nanostructures by double crystalline block copolymers for biomedical applications

 
 
Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Research Group: Systems Biology / Bioinformatics
PhD Project:

Systems based modelling of human fungal pathogens interacting with the human immune system

 
 
Schumann, Martin

publications »

JSMC Fellow

Email »

Institute/Dep.
Friedrich Schiller University Jena
Institute of Geosciences
Mineralogy & Geochemistry
PhD Project:

Microbial origin of banded iron formations

 
 
Schwenk, Daniel

publications »

ILRS Student

Email »

Institute/Dep.
Friedrich Schiller University Jena
Institute of Pharmacy
Dep. of Pharmaceutical / Medicinal Chemistry
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Bio Pilot Plant
PhD Project:

Natural products from an unidentified homobasidiomycete which control wood- deteriorating microorganisms

 
 
Seccareccia, Ivana

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publications »

JSMC Fellow

Email »

Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Junior Research Group
Secondary Metabolism of Predatory Bacteria
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Junior Research Group
Chemistry of Microbial Communication
PhD Project:

Molecular basis for predatory interactions of Cupriavidus necator with its prey bacteria

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Abstract: Many microbiologists know the Gram-negative bacterium Cupriavidus necator (syn. Ralstonia eutropha)1 for its metabolic adaptiveness. The organism usually thrives in soil and freshwater...
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... habitats, where it metabolizes organic substances as sources of carbon and energy.2 In the absence of such compounds, however, the bacterium switches to an autotrophic growth mode.3 To this end, C. necator fixes CO2 via the reductive pentose phosphate cycle.4 The energy that is required for this process comes from the oxidation of molecular hydrogen by two NiFe hydrogenases, corresponding to a biological Knallgas reaction. To sustain its growth under anoxygenic conditions, C. necator possesses a complete denitrification pathway, which allows the usage of alternative electron acceptors, e.g. nitrate or nitrite.5 Its diverse metabolic features clearly make C. necator an allrounder among bacteria that is able to cope with harsh environmental conditions. Of particular interest within the scope of the JSMC are the diverse interactions of this bacterium with other microorganisms. C. necator exploits the transiently available supplies of H2, which arise from the metabolic activity of N2-fixing microbes.6 Furthermore, it was shown to act as a nonobligate bacterial predator of various other gram-positive and gram-negative bacteria in soil.7,8 In fact, the predatory behaviour of C. necator, albeit often neglected, was eponymous for its epithet (L. n. necator, slayer).8 Previous studies have shown that predatory behaviour can be triggered in C. necator by nutrient depletion,9 i.e. predation may represent an alternative to autotrophy. The mode of predation is still barely characterized in C. necator,10 even though its attachment to prey cells8 suggests an epibiotic strategy that does not involve cytoplasmic or periplasmic invasion. In the proposed project, we set out to interrogate the molecular basis of predation in C. necator. We have recently verified the predatory potential of strain H16, adapting a baiting technique that was originally developed for the isolation of predatory myxobacteria from soil.11 C. necator strain H16 is probably best known for the production of bioplastics.12,13 What makes this organism an ideal candidate for our study is the availability of its fully sequenced and annotated genome,14,15 providing a basis for gene inactivations, transcriptomic and proteomic analyses. We will target select genes that are likely to have a role in predation (e.g., pili and adherence genes, genes involved in chemotaxis and toxin production) and analyze the effects of deletions in microscopic studies. References 1. Vandamme, P. & Coenye, T. Taxonomy of the genus Cupriavidus: a tale of lost and found. Int. J. Syst. Environ. Microbiol. 54, 2285-2289 (2004). 2. Balkwill, D. L. Genus Cupriavidus Makkar and Casida 1987. in Bergey’s Manual of Systematic Bacteriology, 2nd edn., Vol. 2 (eds. Boone, D. R., Castenholz, R. W., Garrity, G. M., Brenner, D. J., Krieg, N. R., Staley, J. T.) 600-604, (Springer-Verlag, New York, NY, 2005). 3. Aragno, M. & Schlegel, H. G. The mesophilic hydrogen-oxidizing (knallgas) bacteria. in The Prokaryotes (eds. Balows, A., Trüper, H. G., Dworkin, M., Harder, W. & Schleifer, K.-H.) 344-384, (Springer-Verlag, New York, NY, 1992). 4. Bowien, B. & Kusian, B. Genetics and control of CO2 assimilation in the chemoautotroph Ralstonia eutropha. Arch. Microbiol. 178, 85-93 (2002). 5. Pfitzner, J. & Schlegel, H. G. Denitrifikation bei Hydrogenomonas eutropha strain H 16. Arch. Mikrobiol. 90, 199-211 (1973). 6. Schwartz, E. & Friedrich, B. The H2-metabolizing prokaryotes. in The Prokaryotes: An Evolving Electronic Resource for the Microbiological Community release 3.13, Edn. 3 (eds. Dworkin, M., Schleifer, K. H. & Stackebrandt, E.) (Springer-Verlag, New York, NY, 2003). 7. Casida, L. E. Relation to copper of N-1, a nonobligate bacterial predator. Appl. Environ. Microbiol. 53, 1515-1518 (1987). 8. Makkar, N. S. & Casida, L. E. Cupriavidus necator gen. nov., sp. nov.: a nonobligate bacterial predator of bacteria in soil. Int. J. Syst. Bacteriol. 37, 323-326 (1987). 9. Casida, L. E. Response in soil of Cupriavidus necator and other copper-resistant bacterial predators of bacteria to addition of water, soluble nutrients, various bacterial species, or Bacillus thuringiensis spores and crystals. Appl. Environ. Microbiol. 54, 2161-2166 (1988). 10. Jurkevitch, E. Predatory behaviors in bacteria – diversity and transitions. Microbe 2, 67-73 (2007). 11. Dawid, W. Biology and global distribution of myxbacteria in soils. FEMS Microbiol. Rev. 24, 403-427 (2000). 12. Gorenflo, V., Schmack, G., Vogel, R. & Steinbüchel, A. Development of a process fort he biotechnological large-scale production of 4-hydroxyvalerate-containing polyesters and characterization of their physical and mechanical properties. Biomacromolecules 2, 45-57 (2001). 13. Fukui, T., Abe, H. & Doi, Y. Engineering of Ralstonia eutropha for production of poly(3-hydroxy-butyrate-co-3-hydroxyhexanoate) from fructose and solid-state properties of the copolymer. Biomacromolecules 3, 618-624 (2002). 14. Pohlmann, A., Fricke, W. F., Reinecke, F., Kusian, B., Liesegang, H., Cramm, R., Eitinger, T., Ewering, C., Pötter, M., Schwartz, E., Strittmatter, A., Voß, I., Gottschalk, G., Steinbüchel, A., Friedrich, B. & Bowien, B. Genome sequence oft he bioplastic-producing "Knallgas" bacterium Ralstonia eutropha H16. Nature Biotechnol. 24, 1257-1262 (2006). 15. Schwartz, E., Henne, A., Cramm, R., Eitinger, T., Friedrich, B. & Gottschalk, G. Complete nucleotide sequence of pHG1: a Ralstonia eutropha H16 megaplasmid encoding key enzymes of H2-based lithoautotrophy and anaerobiosis. J. Mol. Biol. 332, 369-383 (2003).
 
 
Senftleben, Dominik

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ILRS Student

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Institute/Dep.
Friedrich Schiller University Jena
Institute of Microbiology
Microbial Communication
PhD Project:

A surface hydrophobin in ectomycorrhiza interaction

 
 
Shitut, Shraddha

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IMPRS Student

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Institute/Dep.
Max Planck Institute for Chemical Ecology
Dept. of Bioorganic Chemistry
Experimental Ecology and Evolution
PhD Project:

Unraveling the dynamics of metabolite production in cross-feeding populations and study its effect on the interactions

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Abstract: No organism exists in isolation in nature. There are numerous interactions taking place; some of which entail exchange of information between microbes. This information has been shown...
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... to be of different types like DNA, metabolites, toxins and so on. My work focuses on the exchange of metabolites between synthetically engineered strains of Escherichia coli and Acinetobacter baylyi. The metabolite being a nutrient (amino acid) also affects the physiology of the partners. Availability of this nutrient in the surrounding could alter internal levels and subsequently the interaction between the partners. Understanding how this exchange is regulated gives an insight of how organisms interact in a community. A major part of the interaction is not only the process but also its result. These interactions in-turn shape the community and also the physiology of the organisms. Another aspect of the study will be to study the interaction between partners with a perspective of experimental evolution. This also throws light on its frequent occurrence in nature.
 
 
Siegismund, Daniel

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JSMC Fellow

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Institute/Dep.
Friedrich Schiller University Jena
Institute for Materials Science and Technology
Dept. of Metallic Materials
Friedrich Schiller University Jena
Dept. of Bioinformatics
PhD Project:

Studying biofilm formation on biomaterials by a combined experimental and theoretical approach – a contribution to win the race for the surface

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Abstract: Bacterial infection in hospitals (nosocomial infection) is an increasing problem in general. It is estimated that about 800.000 cases of nosocomial infections occur in Germany per year....
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... In the USA at least half of such infections are associated with medical devices as, for example, metallic implants in the human skeletal system. Such infections go along with biofilm formation. Bacterial communities of only one or of several species often form so-called biofilms, that is, aggregates of micro-organisms in which cells are stuck to each other and/or to a surface. More than 5 million central venous catheters (CVC) are inserted annually in the US. 2 – 12 % of CVCs insertions result in sepsis. Although the risk for infection concerning hip and knee prosthesis is low (1 – 3 %), the cost of management of a joint infection is estimated to exceed $50,000 per case. Bacteria exist in planktonic and sessile forms. Free floating planktonic bacteria can be attacked by the immune system as well as by antibiotics. However, after settling on a surface, the phenotype changes and an extracellular matrix is formed (e.g. from cellulose) protecting the cells. This results in significantly reduced susceptibility to antibiotics. Furthermore they face a locally weakened immune defense. Perfect hygiene assumed, bacteria may come from two types of sources. The first is the patient’s skin, the air or microbial contamination of the wound (e.g., in case of open fractures), the second is haematogenous or lymphatic seeding from infections somewhere else in the body. In a first step bacteria attach to the surface and start producing an extracellular matrix. When further bacteria have settled, the former change their phenotype and the biofilm is formed. Biofilm formation competes with tissue integration, since human cells, too, try to cover the implant material. Thus, the main goal after implantation is to avoid the formation of a microbial biofilm and promote tissue integration – the so called race for the surface. Despite the large complexity and variety of the parameters, the development of a biofilm can, in principle, be divided into six different stages: A) forming a conditioning film, for example adsorption of water and proteins in the blood stream; B) reversible and irreversible primary adhesion: the meeting between a conditioned surface and a planktonic microorganism. This stage is reversible and is dictated by a number of physicochemical variables, C) the anchoring or locking phase, which employs molecularly mediated binding between specific adhesins and the surface. The presence of one species of microorganism on a surface can promote the adhesion of another. The following stages D, E and F of biofilm formation are controlled by a variety of parameters which are independent of the substrate material. Various investigations were made to influence bacterial adhesion by materials surface proper¬ties, such as chemistry of surface, surface roughness, surface morphology or configuration and surface hydrophobicity or wettability. In general, microorganisms are less attracted by flat, smooth surfaces than by rough or porous surfaces. However, these studies are hard to compare since there are no standard tests for biofilm formation. All these studies are different in conditioning the surface, the type(s) of microbes used, the testing parameters and finally material properties such as "roughness" are not systematically changed. Besides the lack of standard tests for biofilm formation, there will be no opportunity in the near future for in-vitro tests of human cell adhesion and microbial biofilm formation at the same time. Actual test methods focus on in-vivo models. By computer simulation, the two processes could be brought together to analyse the competing process of tissue integration and biofilm formation. The long-term perspective is to substitute experiments with animals by computer simulations. Goal of the present project is to extract hard and weak effects from the high variety of material properties that might influence microbial adhesion. In biotechnology, biofilm reactors have long been commercially used in the treatment of wastewater and off-gas. Additionally, it becomes more and more evident that biofilm technology has an enormous potential in improving efficiency of converting lignocellulose materials to biofuels. Advantages of biofilms include concentration of cell-associated hydrolytic enzymes at the biofilm–substrate interface to increase reaction rates, a layered microbial structure in which multiple species may sequentially convert complex substrates, and fungal–bacterial symbioses that allow simultaneous enzymatic processes of different types. Of special importance in microbial communities is the effect of cheating: some cells cease secreting extracellular enzymes or substances to save metabolic costs, but benefit from the compounds secreted by cooperating cells. This usually impairs productivity. Objective The objective of this proposal is to create a testing device and a simulation tool to investigate material surface properties for the first three stages of biofilm formation. Two PhD students – one experimentalist and one theoretician – are to cooperate closely. The building and validation of models and the planning and realization of experiments will be performed in an iterative, mutually stimulating manner. The proposal is based on a previous feasibility study of the IMT and the HKI in 2004. It was shown that such a testing device can be built and first results revealed qualitative differences. The experimental challenge is to assure reproducibility of the conditions for biofilm formation for every experiment and for the duration of several days. Fig. 1 shows the experimental setup. Up to 12 material samples can be placed in the constant-depth film fermenter and each of them can be removed individually. In a first approach glass slides were covered by half with a PVD layer of titanium. Fig. 2 shows the interface between the uncoated and the coated glass slide after some days of testing with attached Escherichia coli cells.
 
 
Sumanovac Sestak, Ivana

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JSMC Fellow

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Institute/Dep.
Leibniz Institute of Photonic Technology (IPHT)
Dep. of Microscopy
Leibniz Institute for Age Research, Fritz Lipman Institute (FLI)
Dep. Molecular Biology
PhD Project:

Developing a palm-compliant MELC process for the structure elucidation of the human kinetochore

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Abstract: The PhD student will develop a novel mode of microscopy imaging which aims at obtaining structural biological information at a resolution down to about 30nm for many (10-100) target...
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... molecules associated with the kinetochore complex. The methodology is based on combining a high resolution single molecule technique (photo activated localization microscopy, PALM) and addressing the multiple molecular targets by using multi-epitope ligand cartography (MELC). Both of these techniques have been shown to achieve impressive results and thus the combination should be capable of producing extremely valuable scientific information about the organisation of the kinetochore. The three-dimensional molecular structure of the kinetochore is still unknown but is essential for the understanding of its function and its role in cancer development. This project is situated within two highly motivated groups in the interface between Biology (Prof. Stephan Diekmann, Kinetochore complex) and Physics (Prof. Rainer Heintzmann, high resolution microscopy techniques), where experience, team-work and guidance with many aspects of the project will be provided.
 
 
Sundaram, Srividhya

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ILRS Student

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Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Dept. Biomolecular Chemistry
PhD Project:

Elucidation of Complex Biosynthetic Pathways in Microorganisms

 
 
Institute/Dep.
Max Planck Institute for Chemical Ecology
Dept. of Bioorganic Chemistry
PhD Project:

IRMS-Analyse von Terpenduftstoffen

 
 
Teh, Beng Soon

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JSMC Fellow

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Institute/Dep.
Max Planck Institute for Chemical Ecology
Dept. of Bioorganic Chemistry
PhD Project:

Insect gut microbiota: community structure and control

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Abstract: The gut of insects harbors a wide range of microorganisms. The bacteria in the gut directly affect the physiology, development and growth of the insect host. Intestinal gut microbes...
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... play essential role in food digestion, synthesizing vitamins for the host and protection against harmful microbes. The work on the gut of the genus Spodoptera has been extensively studied in our laboratory in recent years. An indigenous biota is present in the gut of all insect species with a role of maintaining stable communities. One of the core bacteria living in the gut of insects is the Enterococcus sp. In our previous studies, E. casseliflavus was detected to be the most abundantly distributed apart from Clostridia and Lactobacilli. It is unknown if strains of these species residing specific niches in the gut and the reasons of colonizing those habitats. Several factors such as pH and redox potential might alter the composition of the microbiota. The gut of insects develops an efficient mechanism to digest their diets leading to different pH and redox potential as part of the adaptation strategies. The different pH gradient within the gut environment of many insects dramatically changes the diversity of gut microbiota. The first aim of this project is to selectively use a dominant single bacterial species, E. casseliflavus as model organism to study its gene expression in response to pH variations in the gut of Spodoptera at different life cycles (larvae, pupae and adults). In order to achieve this objective, single bacterial cells will be tagged with fluorescent gene as a marker to monitor survival of the bacteria along the gut of the insect. In addition, it has been reported that E. casseliflavus live in close proximity with the red crop (crystallization of beta-carotene) in the foregut of Spodoptera larvae upon feeding on toxic plant. We feel that the presence of carotene crystal and the bacteria together might form an unknown mechanism in the adaptation of the insects to toxic food plants. In the second aim of the project, we are particularly interested to uncover the carotenoid uptake mechanism leading to the crystal formation in the foregut of the insect. The gene expression of carotenoid-binding protein will be closely studied.
 
 
Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Research Group Applied Systems Biology
PhD Project:

Agent-based modeling of the spatio-temporal interaction between immune cells and human-pathogenic fungi

 
 
Töpfer, Natalie

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JSMC Fellow

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Institute/Dep.
University Hospital Jena
Septomics Research Centre
Leibniz Institute of Photonic Technology (IPHT)
Dep. Spectroscopy/Imaging
PhD Project:

Characterization of pathogen-leukocyte interaction by means of Raman spectroscopy

 
 
Tovar, Miguel

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JSMC Fellow

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Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Bio Pilot Plant
PhD Project:

Exploiting the metagenomic and biosynthetic diversity of microbial communities on a droplet-based microfluidic platform for the screening of novel natural products

 
 
Tuppatsch, Katja

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Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Dept. Molecular and Applied Microbiology
PhD Project:

Redox regulation, development and hyphal growth in Aspergillus nidulans

 
 
Ullah, Chhana

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JSMC Fellow

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Institute/Dep.
Max Planck Institute for Chemical Ecology
Dept. of Biochemistry
PhD Project:

Chemical communication between biotrophic and necrotrophic pathogens and a woody plant host: Signaling, defense reactions, and the cost of defense

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Abstract: Plants are subject to infection by two different classes of pathogens: biotrophic pathogens, which infect plant cells but do not actually kill them, and necrotrophic pathogens, which...
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... obtain their nutrients from dead or dying cells. Biotrophs are known to communicate closely with plants via effector proteins that maintain pathogenesis. Plant R-protein receptors are designed to recognize the effector proteins of biotrophs and signal a defense response, but biotrophs may be able to evade recognition. In contrast, the communication of necrotrophs with their hosts is much less well understood. Plants are hypothesized to recognize necrotrophs by the pattern of molecules produced on infection and respond by synthesizing defensive compounds. But, it is unclear how plant defenses function against necrotrophic vs. biotrophic pathogens given the different scales of contact and types of communication. Necrotrophic infection must be opposed by blocking pathogen growth at a distance from living plant cells, while biotrophs need to be selectively killed within living cells. Not enough is known about which plant compounds are active in defense to determine how they target different pathogen types. Moreover, rarely has anyone considered the costs of antifungal defenses to the plant for different pathogen types. Many pathogens are not necessarily fatal to woody plants. It would be valuable to compare the potential loss of tissue to pathogens and the costs of defending it by measuring carbon and nutrient allocation patterns in plants manipulated to be both with and without defenses. These results should give unique insights into the optimization of plant defense strategies. In recent years, many species of poplar (Populus) have gained economic importance due to their fast growth and use for bio-fuel and timber. The availability of a complete genome for one species has quickly established Populus as the best model system in woody plant research. However, under natural conditions, poplar trees face a plethora of biotrophic and necrotrophic pathogens. In their leaves and bark, poplars synthesize high quantities of polyphenolic metabolites, including proanthocyanidins, flavonoids and salicinoids, which may have anti-fungal properties. Although similar compounds are present in many other woody plant species, their benefit in defense against pathogens of different types and their metabolic costs are still poorly understood. We propose to compare plant-pathogen interactions between black poplar (P. nigra), a species native to Germany, and its two most important pathogens, the biotrophic poplar rust (Melampsora larici-populina) and the necrotrophic poplar canker (Cryptodiaporthe populea). The project will exploit the genomic sequence obtained from Populus trichocarpa, our knowledge of poplar polyphenolic metabolites thought to be important in anti-fungal defense, and the ecological, chemical and molecular platforms already established for studying poplar-herbivore interactions in our laboratory. The goal is to understand: (1) the differences in communication between poplar and biotrophic vs. necrotrophic pathogens (2) how these affect the strategies of plant defense, and (3) the costs and benefits of such defense.
 
 
Üzüm, Zerrin

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JSMC Fellow

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Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Dept. Biomolecular Chemistry
PhD Project:

Bacterial endosymbionts in plant-pathogenic fungi

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Abstract: The plant-pathogenic fungus Rhizopus microsporus and the bacterium Burkholderia rhizoxinica form a unique symbiosis, in which the fungus hosts the bacterial endosymbiont for the...
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... production of a phytotoxin causing rice seedling blight (Nature 2005). Interestingly, reproduction of the fungal host has become totally dependent of the bacterial symbiont (Curr Biol 2007). Analysis of the whole genome sequence of B. rhizoxinica (BMC Genomics 2011) has granted insights into the evolution and the genetic potential of endofungal bacteria. In this project we aim at studying the molecular basis of the bacterial-fungal interaction at the genetic, biochemical and chemical levels.
 
 
Vahabi, Khabat

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Institute/Dep.
Friedrich Schiller University Jena
Institute of General Botany and Plant Physiology
Dept. of Plant Physiology
PhD Project:

Role of AGC kinases in beneficial plant-microbe-interactions

 
 
Voit, Annekatrin

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GRK1257 Student

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Institute/Dep.
Friedrich Schiller University Jena
Institute of Microbiology
Microbial Communication
PhD Project:

Quantification of Streptomycetes in metal-contaminated soil

 
 
Wadke, Namita

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JSMC Fellow

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Institute/Dep.
Max Planck Institute for Chemical Ecology
Research Group Insect Symbiosis
PhD Project:

Biochemistry and ecology of stilbene detoxification by fungal plant pathogens

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Abstract: The success of many plant pathogens is linked to their ability to detoxify the chemical defenses of their hosts. Stilbenes are antifungal defenses found in several important crop...
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... plants, yet some stilbene-containing plants are still susceptible to pathogens. This project will investigate whether pathogens are able to detoxify stilbenes. The work will include research on potential detoxification reactions and enzymes as well as genetic alteration of fungi to investigate the contribution of detoxification processes to fungal fitness.
 
 
Waschina, Silvio

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JSMC Fellow

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Institute/Dep.
Friedrich Schiller University Jena
Theoretical Systems Biology
Dept. of Bioinformatics
Max Planck Institute for Chemical Ecology
Dept. of Bioorganic Chemistry
Experimental Ecology and Evolution
PhD Project:

Evolutionary Systems Biology of Metabolic Microbial Interactions

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Abstract: Cooperative metabolic interactions in microbial communities occur when certain compounds are exchanged between two or more parties in the consortia while each party receives a mutual...
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... benefit. Such mutualisms are from high ecological importance and occur during biofilm formation, quorum sensing and degradation of waste products. A foundational question in evolution of metabolic mutualisms is: Why does a species exhibits a costly metabolic function that benefits another species and, at time same time, coercively depends on actions performed by the partner instead of accomplishing all necessary metabolic functions by itself? For my PhD project, I put the emphasis on a systematic assessment of the costs and benefits that shape the balance between metabolic independence and dependence. Using large-scale metabolic models I plan to identify the environmental and genetic circumstances under which metabolic cooperation can evolve and persist over time. The models are going to be further used to make precise predictions for cooperative interactions between different strains of Escherichia coli, which will be tested with experimental studies.
 
 
Weber, Jakob

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JSMC Fellow

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Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Dept. Molecular and Applied Microbiology
PhD Project:

Discovery of secondary metabolites from Aspergillus fumigatus utilizing post-transcriptional histone modifications

 
 
Institute/Dep.
Friedrich Schiller University Jena
Institute for Inorganic and Analytical Chemistry
PhD Project:

Exploration of a tripartite partnership between green algae and bacteria: From epiphytic bacterial communities to biofilm formation with Ulva sp.

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Abstract: The marine macroalga Ulva mutabilis (Chlorophyta) is developing properly only in association with the two bacterial strains Roseobacter sp. and Cytophaga sp. or morphogenetic compounds...
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... extracted from the bacterial supernatant. Axenic U. mutabilis gametes develop parthenogenetically into callus-like colonies consisting of undifferentiated cells without normal cell walls. Interestingly, the Roseobacter species exhibits a specific chemotactic affinity to the rhizoid cells of U. mutabilis and seems to cooperate with the Cytophaga strain by chemical communication. We are particularly interested in deciphering the cross-kingdom cross-talk from the “first contact” of axenic U. mutabilis gametes with its symbiotic bacteria till the formation of a tripartite system by molecular biological and biochemical approaches. Chemotaxis assays will prove the chemotactic behavior of bacteria to algal-derived extracts. An important aim of this project is to identify the bacterial perception system of these algal infochemicals by applying a transposon knock-out library of Roseobacter. Upon random transposon insertion mutagenesis tetracycline resistant mutants will be tested in chemotaxis assays with Ulva gametes. This project also includes a phenotypic characterisation of the Cytophaga and Roseobacter strains as well as the localisation of the bacteria in the tripartite community via fluorescence in situ hybridization.
 
 
Werner, Sarah

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JSMC Fellow

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Institute/Dep.
Friedrich Schiller University Jena
Dept. of Bioinformatics
PhD Project:

Mathematical modelling of communication between micro-organisms

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Abstract: The work in this PhD studentship will deal with the mathematical modelling and computer simulation of intra- and inter-species signalling between micro-organisms. Specific examples may...
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... be quorum sensing among bacteria, the use of faked signals to cheat prey or hosts or the mutual exchange of intermediates in the production of trisporic acid between mating types in fungi (in particular, Mucorales). An special point to be analysed is the "depth of sensing", that is, is one organism sensing that the other is sensing the presence of the former, and so on. Various methods from mathematical biology and bioinformatics are to be used, e.g. evolutionary game theory and metabolic modelling. The work will be done in cooperation with experimental groups in the Graduate School. Applicants should have a Master's, excellent Bachelor's or diploma degree in a Natural science discipline, programming skills and, preferentially, experience in mathematical modelling of biological processes.
 
 
Wilde, Julia

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JSMC Fellow

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Institute/Dep.
Max Planck Institute for Chemical Ecology
Dept. Molecular Ecology
PhD Project:

The effect of arbuscular mycorrhizal infection on the fitness of Nicotiana attenuata in the field

 
 
Winkler, Thomas

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JSMC Fellow

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Institute/Dep.
Friedrich Schiller University Jena
Institute of Organic Chemistry and Macromolecular Chemistry
Chair for Organic Chemistry I
PhD Project:

Semisynthetic Nosiheptide Derivatives Enabling an Improved Selectivity Profile

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Abstract: Abstract: The natural product nosiheptide (1) will be obtained by fermentation and its scaffold (2) modified by chemical synthesis in order to uncover novel or improved properties....
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... These compounds will be screened for improved activity and selectivity and tested for their regulatory impact on colonies of receptive, mostly soil-dwelling bacteria (Streptomyces, Nocardia, Bacillus, Rodococcus sp.). Objectives: 1) Overproduction of nosiheptide on gram scale 2) Development of synthetic methodology for semisynthetic scaffold variation 3) Syntheses of a focused library of approx. 15?25 compounds 4) Threefold profiling for antimicrobial (70S ribosome), antimalarial (20S proteasome), and microbial signaling (TipAL-induction). 5) Tracking of selective candidates with a focus on microbial signaling. Details: Nosiheptide (1) belongs to the thiopeptide natural products and is one of the most potent antibiotics in vitro known to man, but too insoluble and chemically too unstable to be used for human therapy.[1,2] Its enormous activity stems from extremely potent blockade of the bacterial ribosome (pM range).[3,4] Further activities of thiopeptides include proteasome modulation[5] and induction of the TipAL promoter system,[6] a merR-family regulator.[7] In order to uncover highly active compounds with a selective mode of action, this project will explore semisynthetic derivatization of 1, which is easily fermented in high yield (up to 2g/L) [8, 9]. Nosiheptide will be purified by chromatography and crystallization [1,8] and chemically transformed to a core scaffold (2). This scaffold will be synthetically evolved by using both established [3,4] and new techniques featuring acylation, alkylation, ester- and amide formations, Michael additions, and ring closures. These operations will generate an initial collection of compounds (15-25) in sufficient amounts for characterization and testing (5-20 mg each). The compounds will be profiled in assays for bacterial growth, protein biosynthesis inhibition and proteasome modulation, which will be carried out along established techniques in the lab. To monitor TipAL induction it is planned to set up an appropriate assay [10, 11] Specific focus will then be on uncovering independent chemical triggers/modulators for the three major modes of action of the thiopeptide antibiotics. This project will synergistically benefit from concurrent activities in the Arndt lab thiopeptide team, including total syntheses of thiazolo-peptide natural products, investigations on the mode of action at the proteasome, computational modeling of thiopeptide target interactions, and ribosomal assays. Impact: This project is expected to yield new chemical candidates for antimicrobial and antimalarial applications and to shine light on the regulatory principles connected to thiopeptide antibiotics. The interdisciplinary training will qualify the candidate for advanced research and leadership positions in Chemical Biology and Drug Development. References: 1) T. Prange, A. Ducruix, C. Pascard, J. Lunel, Nature 1977, 265, 189. 2) M. C. Bagley, J. W. Dale, E. A. Merritt, X. Xiong, Chem. Rev. 2005, 105, 685. 3) S. Schoof, S. Baumann, B. Ellinger, H.?D. Arndt, ChemBioChem 2009, 10, 242. 4) H. R. A. Jonker, S. Baumann, A. Wolf, F. Hiller, S. Schoof, K. W. Schulte, K. N. Kirschner, H. Schwalbe, H.?D. Arndt, Angew. Chem. Int. Ed. 2011, 50, 3308. 5) S. Schoof, G. Pradel, M. N. Aminake, B. Ellinger, S. Baumann, M. Potowski, Y. Najajreh, M. Kirschner, H.?D. Arndt, Angew. Chem. Int. Ed. 2010, 49, 3317. 6) T. Murakami, T. G. Holt, C. J. Thompson, J. Bacteriol. 1989, 171, 1459 7) N.L. Brown, J.V. Stoyanov, S.P. Kidd, J. L. Hobman, FEMS Microbiol. Rev. 2003, 27, 145. 8) F. Benazet et al., Experientia 1980, 36, 414. 9) X. Zhang, M. Fen, X. Shi, L. Bai, P. Zhou, Appl. Microbiol. Biotechnol. 2008, 78, 991. 10) D. J. Holmes, J. L. Caso, C. J. Thompson, EMBO J. 1993, 12, 3183 11) L. Dong, N. Nakashima, N. Tamura, T. Tamura, FEMS Microbiol Lett. 2004, 237, 35 12) S. Baumann, S. Schoof, M. Bolten, C. Haering, M. Takagi, K. Shin?ya, H.?D. Arndt, J. Am. Chem. Soc. 2010, 132, 6973 13) B.?S. Yun, T. Hidaka, T. Kuzuyama, H. Seto, J. Antibiot. 2001, 54, 375.
 
 
Wirth, Sophia

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JSMC Fellow

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Institute/Dep.
Friedrich Schiller University Jena
Institute of Microbiology
Microbial Communication
PhD Project:

Volatilome of Schizophyllum commune

 
 
Wissuwa, Bianka

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Institute/Dep.
University Hospital Jena
Clinic of Anaesthesiology and Intensive Care Medicine
Research Unit Experimental Anesthesiology
PhD Project:

Interaction of Heme and Heme degradation products with Slo-1 Channel as a pathomechanism of septic shock

 
 
Zhang, Xiaoyuan

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Institute/Dep.
Friedrich Schiller University Jena
Institute for Materials Science and Technology (IMT)
PhD Project:

Highly Oriented Nanostructured Surfaces of Block Copolymer for Biomedical Applications

Abstract: During the last decades, one of the major trends in the biomaterial research has been the functionalization of the material surfaces to control the biological response of the host...
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... (human body) to improve the biocompatibility. Prevention of nonspecific protein adsorption and microorganisms adhesion on biomatetial surfaces play key roles for successful integration of implants into the human body. It was reported that fabrication of biomaterial surfaces with different nanostructures, especially with different chemical and physical properties, is an effective method to control the protein adsorption and the microorganisms adhesion. So far, only few work focused on the influence of both topographical and chemical surface properties on the protein and microorganisms behavior. Melt-drawn amphiphilic block copolymer thin films are excellent 2D model surfaces to investigate the interaction between surface properties and proteins as well as microorganisms. These functional biomaterial thin films have potential use for broad biomedical applications, e.g., tissue engineering, antimicrobial mat, drug delivery, and optical device/biosensor application. The aim of this research is to investigate the influence of functional block copolymer surfaces with different nanotopographies and chemical properties on protein and microbial adhesion.
 
 
Institute/Dep.
Friedrich Schiller University Jena
Institute of General Botany and Plant Physiology
Chair for General Botany
PhD Project:

The Role of Photoreceptors in Photoperiodic Control in the Green Alga Chlamydomonas reinhardtii

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Abstract: Plants and animals measure the duration of the day and night in the natural environment for sensing the season of the year, known as photoperiodic control. Thereby, components of the...
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... circadian clock and photoreceptors are involved as shown in the underlying molecular mechanism of the long-day plant Arabidopsis thaliana (Fuijwara et al., 2008, Plant Cell 11:2960-71; Miyata et al., 2011, Plant Signal Behav 8:1162-71). While photoperiodic control is well documented in multicellular organisms, relatively little is known in unicells. One of the few reports of a photoperiodic response includes Chlamydomonas. In the well-known life cycle of this alga, non-optimal conditions provoke the differentiation of haploid vegetative cells into gametes, which form zygotes after fusion. Zygotes resist stressful environmental conditions, thus adapting to seasonal changes such as overwintering. It has been shown that the germination efficiency of Chlamydomoans zygospores is enhanced under long-day conditions (Suzuki and Johnson, 2002, Naturwissenschaften 89:214-20; Mittag et al., 2005, Plant Physiol 137:399-409). Based on the full genome sequence of C. reinhardtii (Merchant et al., 2007, Science 318:245-50) (putative) photoreceptors have been found that may be in functional connection to the circadian clock (Schulze et al., 2010, Protoplasma 244:3-14). Recently, some photoreceptor mutants were generated by an insertional mutagenesis approach and are currently under investigation. The aim of this project is to examine the role of different photoreceptors in Chlamydomonas in the molecular mechanism of photoperiodic control and thereby analyze the potential relationship to the circadian clock. Also, the molecular mechanism of photoperiodic control in a unicell will be compared to that of Arabidopsis in collaboration with the lab of Tsuyoshi Mizoguchi (Japan). It is envisaged that the successful PhD candidate joins the lab in Japan for a few months to also work there on the project.