Doctoral Researchers

 
Baldeweg, 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
Secondary Metabolism of Predatory Bacteria
PhD Project:

A natural product as a mediator of virulence in Ralstonia solanacearum

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Abstract: The soil bacterium Ralstonia solanacearum is an economically relevant plant pathogen with a remarkably broad host range. A genome mining study in R. solanacearum led to the discovery of...
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... a biosynthesis gene cluster, which could not be correlated with a known natural product. Targeted inactivation of a biosynthesis gene within this cluster yielded a mutant strain with significantly attenuated virulence in tomato plants. This finding suggests that the gene cluster is expressed in planta, and it also implies an involvement in the production of a novel and likely relevant phytotoxin. The aim of this project is to isolate the corresponding natural product and to elucidate its structure. Once the compound is characterized chemically, we will be in an ideal position to explore its biological effects. Evidence confirming the involvement of a natural product in the virulence of R. solanacearum would be of significant consequence from a phytopathological perspective and revolutionize our understanding of the pathogenesis of bacterial wilting diseases. From a chemical perspective, this study will close the existing gap in the secondary metabolome of R. solanacearum and set the stage for comprehensive analyses on the role of natural products in plant-microbe communication.
 
 
Barnett, 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-
Junior Research Group
Chemistry of Microbial Communication
PhD Project:

Discovery of Small Molecule Inhibitors of Multicellular Development

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Abstract: What are the small molecules that orchestrate, or interfere with, multicellular associations in eukaryotes?
The social amoeba Dictyostelium discoideum represents one of the...
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... earliest branches of the common ancestor of all eukaryotes. It is thus an ideal model organism to study general eukaryotic communication and cellular mechanisms. Since it can exist both in a single-cell and a multicellular state, D. discoideum serves as a paradigm in understanding the onset of multicellularity. Differentiation and multicellularity in this protist have evolved in a setting where they are surrounded by food sources (e.g. bacteria), as well as predators. Only in the light of this ecologically relevant context, a deep understanding of the fundamental molecular communication and signaling processes can be gained. Understanding how small molecules selectively interfere with the early eukaryote’s association machinery will provide us with insight for deciphering and modulating basic cellular mechanisms.
The social amoeba D. discoideum typically preys on bacteria, yet it can also serve as a food source for the related dictyostelid D. caveatum. [1] This feature was first described 30 years ago and has since been subject to further investigations. Importantly, D. caveatum can only feed on D. discoideum, if the latter is present in the single-cell state. Previous studies have shown that D. caveatum secretes a factor that effectively freezes D. discoideum in the single cell state, by inhibiting formation of the multicellular fruiting body (Fig. 1). While preliminary experiments clearly show that a small diffusible molecule is the responsible morphogenesis inhibitor, its structure, biosynthesis, and mode of action remain elusive.
While preliminary experiments clearly show that a small diffusible molecule is the responsible morphogenesis inhibitor, its structure, biosynthesis, and mode of action remain elusive. [2] We utilize bio-assay guided fractionation to attempt to isolate and elucidate the structure of the small molecule responsible for the inhibition of multicellular development in Dictyostelium discoideum.
 
 
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).
 
 
Beliaev, Ivan

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Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Research Group Applied Systems Biology
 
 
Benndorf, René

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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
Chemical Biology of Microbe-Host Interactions
PhD Project:

Investigation of secondary metabolites from insect-associated microbes and their contribution to insect homeostasis and defense

 
 
Beretta, Martina

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JSMC Fellow

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Institute/Dep.
University Hospital Jena
Clinic of Anaesthesiology and Intensive Care Medicine
Sepsis Research
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.
 
 
Bigalke, Arite

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ChemBioSys Student

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

Algizidal bacteria in plankton communities: resistance, lysis and hetereotrophy

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Abstract: This project focuses on the role of secondary metabolites as mediators of the complex plankton community structure. Plankton comprises any organisms that live in the water column and...
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... are incapable of swimming against a current. Numerous species of these often microscopically small organisms co-exist in the water columns and the species diversity in the homogeneous environment has fascinated scientists since the early days of microscopy. Besides fluctuating resources, chemical signals have more recently been identified as key players in the shaping of communities. But even if we know a few metabolites that have the potential to influence single species the role of such metabolites in structuring a complex community is still little. The starting point of this project is the observation that certain bacteria can lyse algae within a phytoplankton bloom to potentially exploit the released resources. The lytic bacterium Kordia algicida is capable of lysing entire algal blooms thereby massively influencing plankton dynamics in the sea. Lytic activity is controlled by quorum sensing type signaling and relying on the release of extracellular digestive enzymes, such as proteases. However specific algae, such as the diatom Chaetocerous dydimus are resistant against these bacteria. We will now follow up initial evidence of an induced resistance of the alga that releases proteases itself once it gets in contact with exudates from the bacteria. We will characterize the signal perception and the mechanism of induction of the chemical defense. Therefore we will use bioassay guided structure elucidation to identify the cues from K. algicida that are perceived by the algae, further we will explore the full metabolic response of the alga to identify mechanisms of adaptation besides protease release. This response will be characterized using elaborate GC/MS and LC/MS comparative metabolomics with a broad coverage. Our studies will also explore the role of lytic bacteria in a mixed community of susceptible and resistant alga species. Here we will follow up on initial results that indicate a substantial amount of heterotrophy in marine microalgae. We will extent the above described etabolomics platform established for the alga/bacteria interaction using by isotope labeling techniques. This will allow following up the fate of nutrients released by the lysed alga. Thereby we can monitor if the resistant alga benefits from the activity of the lytic bacteria. We will also explore the role of competition between these two partners that potentially exploit the same resources. Experiments will initially be conducted in lab experiments where microcosms for co-culturing of plankton species and simple communities are available. Once the responses are characterized and methods are in place we will conduct full-scale mesocosm experiments during phytoplankton blooms to find out more about potential cascading effects on the entire plankton community during events of bacterial control of blooms. Mesocosms will be selectively enriched with lytic bacteria and / or resistant algae and the performance of all introduced partners as well as of key players of the natural plankton community will be monitored. Using this elaborative approach we will be able to explore the potential complexity of plankton signaling and learn more about approaches for ecosystem conservation as well as for large scale industrial culturing of microalgae.
 
 
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.
 
 
Braga de Lima, Daniel

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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 Pharmaceutical Biology
PhD Project:

Investigation of multimodular biosynthesis enzymes in agaricomycetes

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Abstract: It is well established that small molecules mediate organismal interactions among eu -or prokaryotic microbes, or between them, e.g., through quorum sensing, inhibition, or inducing...
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... effects on metabolism. Recent progress in basidiomycete genomics unveiled a remarkable number of genes dedicated to small molecule biosynthesis, e.g. polyketides or small peptides. In stark contrast, little is known about the structures (let alone their bioactivities) of these secondary products and their effects on other microbial cells in subinhibitory concentrations, i.e., those titers that typically occur in shared habitats under natural environmental conditions. This ILRS project aims at research into the structural diversity of basidiomycete natural products and the effects they exert on other microbial cells. Specifically, parasitic species of the agaricomycotina (mushroom-type “higher fungi”) will be characterized for their secondary metabolome, with an emphasis on polyketides. In a higher level, we expect to gather information about the role of these microorganisms in the microbial community and evidences about polyketide biosynthesis in mushroom -type fungi. We combine chemical analytics with genetic methods, to identify biosynthesis genes and connect them with fungal natural products. Their interactive relevance on other microbes and microbial communitie s will be investigated by specifically engineered reporter strains and activity-guided assay procedures.
 
 
Brandt, Philip

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JSMC Fellow

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

Basidiomycete polyketides as potential mediators in organismal interactions

 
 
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.
 
 
Bratovanov, Evgeni

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ChemBioSys Student

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

Bacterial-fungal interactions

 
 
Bredy, 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-
Dept. Biomolecular Chemistry
PhD Project:

Cryptic Natural Products in Interactions of Anaerobic Bacteria