Doctoral Researchers

 
Abdulsalam, Oluwatosin

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JSMC Fellow

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

Geosmin in the mycorrhizosphere of tricholoma vaccinum

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Abstract: Geosmin, a major contributor to the petrichor (earth smell) observed post-rain fall after a long spell of dryness, is a volatile chemical mainly produced by members of the genera...
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... Streptomyces. Although, many other organisms have been shown to produce this distinctly-smelling volatile, a recent discovery was made that our test organism, Tricholoma vaccinum, produces geosmin. Geosmin being a volatile organic compound (VOC) and with the numerous amount of research on the role of VOCs in communication between biological systems, we therefore are interested in understanding the role of geosmin in the communication between Tricholoma vaccinum and its norway spruce host, Picea abies. We are also interested in understanding the role of geosmin in Tricholoma vaccinum’s microbial community structure establishment. As part of the prelimnary experiments, representative community members of the mycorrhizosphere of Tricholoma vaccinum will be isolated and effects of the interaction between them and Tricholoma vaccinum will be investigated. Also, biosynthesis and the route of biosynthesis of Geosmin in Tricholoma vaccinum will be confirmed and mutants will be generated to help in the analysis of volatile functions in communication, community structure establishment and mycorrhization.
 
 
Aiyar, Prasad

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ILRS Student

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

Molecular dissection of early signaling response in the green alga Chlamydomonas reinhardtii under the influence of biotic and abiotic factors

 
 
Al-Zaben, Naim

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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 Applied Systems Biology
PhD Project:

Quantitative Analysis of Intercellular Communication from Live Cell Imaging

 
 
Allert, Stefanie

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FungiNet Student

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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.
 
 
Aurin, Marc-Benjamin

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ILRS Student

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

How do phytoplasmas generate ‘zombie plants’? Interaction of the bacterial effector protein SAP54 with floral homeotic proteins

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Abstract: Phytoplasmas are pathogenic bacteria that are obligate parasites of plants and transmitting insects [1 3]. They can cause devastating plant diseases, e.g. by reprogramming development...
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... in a way such that leaf-like structures instead of floral organs occur. Infected plants are thus often sterile, mainly serve to reproduce phytoplasmas and hence have been termed ‘zombie plants' [1, 3]. The molecular mechanism underlying the developmental reprogramming relies on specific interactions of a secreted phytoplasma protein called SAP54 (or PHYLLOGEN1) with a subset of MIKC-type MADS-domain transcription factors involved in controlling flower development [1, 2]. The secreted part of SAP54 interacts with the keratin-like domain (K domain) of MIKC proteins and destines them for degradation [1], so that they cannot constitute ‘floral quartets’ anymore, the protein complexes that specify floral organ identity [4]. Based on the recently published X-ray crystal structure of a K domain and detailed in silico analyses [5, 6] we have developed three hypotheses: i) SAP54-like proteins form a structure which is very similar to that of the K domain; ii) The interaction between SAP54 and the plant MIKC proteins is mediated by a mechanism that resembles the interaction of two K domains in floral quartets; iii) SAP54 mimics the K-domain structure as a result of convergent protein evolution [6]. We want to test these hypotheses by determining the structure of SAP54-like proteins and studying the interaction between these proteins and MIKC proteins. References 1. MacLean AM, et al. (2014) PLoS Biol 12, e1001835 2. Maejima K, et al. (2014) Plant J 78, 541-554 3. Du Toit A (2014) Nature Rev Microbiol 12, 393-393 4. Gramzow L, Theißen G (2010) Genome Biol 11, 214 5. Puranik S, et al. (2014) Plant Cell 26, 3603-3615. 6. Rümpler F, et al. (2015) Trends Plant Sci (in press)
 
 
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

 
 
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.
 
 
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

 
 
Brandt, Philipp

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FungiNet Student

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Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute (HKI)
Junior Research Group Host Fungal Interfaces
PhD Project:

Regulation of Candida albicans virulence traits by protein kinases

 
 
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

 
 
Carrasco Flores, David

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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:

Establishing a model system for studying abiotic and biotic interactions of a flagellate green microalga in the marine environment

 
 
Conrad, Theresia

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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:

Multilevel modelling of human-pathogenic fungi and the host immune system

 
 
Dadi, Temesgen Hailemariam

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Institute/Dep.
PhD Project:

computational methods for metagenome analysis

 
 
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

 
 
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.
 
 
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.
 
 
Esken, Jens

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ILRS Student

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

Induction of tetrachloroethene respiration in Sulfurospirillum multivorans

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Abstract: Dehalogenation processes driven by natural microbial communities contribute significantly to the global halogen cycle. Such microbial networks include organohalide-respiring bacteria,...
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... which couple the reductive dechlorination or debromination of halogenated organic compounds to energy conservation via a chemiosmotic mechanism. The key enzyme in organohalide respiration is the reductive dehalogenase (RDase), which serves as a terminal reductase. The RDases are iron-sulfur proteins that harbor a corrinoid cofactor at the active site. Organohalide respiration was studied in detail in the tetrachloroethene (PCE)-dechlorinating epsilonproteobacterium Sulfurospirillum multivorans. The organism displays an unusual type of long-term down-regulation of the PCE reductive dehalogenase gene (pceA) expression in the absence of PCE. In close proximity to pceA, open reading frames encoding putative regulatory proteins were identified. The ILRS project aims to determine the role the corrinoid cofactor of the RDase in the long-term regulation of PCE respiration. In addition, the project focuses on the characterization of two-component regulatory systems within the organohalide respiration gene region in S. multivorans and on the molecular mechanism of PCE sensing.
 
 
Ferling (née Viediernikova), Iuliia

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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:

The role of virulence determinants of the human pathogenic fungus Aspergillus fumigatus in the defense against fungivorous amoeba.

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Abstract: Infections with opportunistic pathogens are among the leading causes of morbidity and mortality in humans. The filamentous fungus Aspergillus fumigatus represents a classical example...
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... foe this group, as it normally thrives as saprophyte in the soil, but disperses asexual conidia as infectious agents. Upon inhalation by immunocompromised host, these conidia can germinate and invade the surrounding tissue. Lethality of such an invasive aspergillosis is high due to limited diagnostic and therapeutic options. A multitude of general virulence factors can lead to invasive growth and rapid disease progression with often enormously high death rates, exceeding even 90% in certain patient cohorts (Brakhage and Langfelderk, 2002). Little is known on the evolutionary origin of this armory. In a recent sturdy we could show that two major virulence determinants, formation of the protective DHN-melanin and the second metabolite gliotoxin are also effective against the soil amoeba Dictyostelium discoideum (Hillmann et al., 2015). An amoeba defensive function was also detectable for trypacidin, a spore born toxin of A. Fumigatus with antiphagocytic properties (Mattern et al., 2015). These results supported the idea some basic mechanisms of fungal virulence could have emerged long before the appearance of innate immune systems and foster the hypothesis that they could be driven from the selection pressure imposed by amoeba predation. A central question of my thesis is therefore if interactions with fungivorous amoeba could have stimulated the development of such virulence mechanisms. To address this point I will exploit an extended model system based on the amoeba Protostelium mycophaga, an obligate fungivore which was isolated from a forest site near Jena. Preliminary results in the group of Falk Hillmann indicate that P. mycophaga has wide food spectrum of ascomycetous or basidiomycetous yeasts, but can also attack fungal hyphae. My work program will analyze the molecular interactions with fungal conidia during phagocytosis, but will include first approaches to analyze the chemical communication between these two antagonistic organisms.
 
 
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.
 
 
Ferreira Lobo da Graça, Ana Patrícia

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

Biosynthesis and function of the cryptic cofactor mycofactocin

 
 
Flak, Michal

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Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Dept. Molecular and Applied Microbiology
 
 
Förster, Toni

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FungiNet Student

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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.
 
 
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”.
 
 
Fürst, David

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

Influence of microorganisms on the phytoremediation-potential of different plants on heavy-metal contaminated soils

 
 
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.
 
 
Garbe, Enrico

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Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute (HKI)
Junior Research Group Host Fungal Interfaces
PhD Project:

Transcriptional control of environmental pH modulation in the fungal pathogen Candida albicans

 
 
Gore, Sagar

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ChemBioSys Student

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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:

Pattern recognition methods for prediction of chemical structure of fungal secondary metabolites

 
 
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.
 
 
Häder, Antje

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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:

Genome-wide identification of risk markers during the immune response towards pathogens of systemic infections

 
 
Hanf, Benjamin

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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:

Low temperature stress of filamentous fungi

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Abstract: Fungi naturally encounter sharp temperature shifts in their environment. In this context, some fungi have evolved protective mechanisms to be more resistant against low temperatures....
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... Further on, silent gene clusters can be induced due to the initiation of new stress factors. Little is known about the adaptation to cold and cryo stress in Ascomycetes. To identify the key processes induced at low temperatures, the proteome such as the secondary metabolite production of the well-studied filamentous fungus Aspergillus nidulans was analyzed under defined cold stress conditions in a comparative gel-based (DIGE) and gel-free (LC-MS/MS) proteomic approach. Further on, the formation of secondary metabolites will be identified by LC-MS/MS. Another focus of this study will be the investigation of post-transcriptional changes, particularly the acetylome, which is currently completely unknown for the species Aspergillus. First insights should be provided into the regulation of different proteins in A. nidulans after inducing cold stress. In addition, different experimental methods should be combined to develop an improved identification of activated secondary metabolite biosynthesis gene clusters. This work will be complemented by transcriptional profiling of the cold stress response in A. nidulans. Interesting genes or proteins will be further analyzed by molecular biological techniques. Most likely, the generated data may support the development of new approaches to optimize the cryopreservation of fungi and may reveal putative anti-freezing-proteins or new osmoprotectants which could lead to an advanced long-term storage of fungi or other organisms.
 
 
Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Bio Pilot Plant
PhD Project:

Optofluidic study and characterization of microbial communities in a novel droplet-based microfluidic system with integrated optical fibers

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

TFP TV9

 
 
Hermenau, Ron

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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:

Chemical Mediators in the Interaction between Bacteria and Plants/Fungi

 
 
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).
 
 
Hoang, Mai

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JSMC Fellow

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Institute/Dep.
University Hospital Jena
Department for Internal Medicine II
Haematology and Medical Oncology
PhD Project:

Characterisation of Aspergillus fumigatus mutants regarding their interaction with human leucocytes

 
 
Hölscher, Theresa

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IMPRS Student

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Institute/Dep.
Friedrich Schiller University Jena
Institute of Microbiology
Junior Research Group Terrestrial Biofilms
Max Planck Institute for Chemical Ecology
Dept. of Bioorganic Chemistry
Experimental Ecology and Evolution
PhD Project:

Effect of spatial constrains of public good production on microbial community assortment

 
 
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.
 
 
Irmscher, Sarah

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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:
Infection Biology
Friedrich Schiller University Jena
Institute of Nutrition
PhD Project:

Analysis of the molecular interaction of the human pathogenic fungus Candida albicans with macrophages

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Abstract: The human pathogenic yeast Candida albicans escapes the immune response of the human host via different immune evasion strategies. C. albicans induces the adaptive as well as the innate...
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... immune system of the host including formation of antimicrobial peptides, attack by phagocytic cells, and complement activation. C.albicans activates all three complement pathways: the classical pathway by antibodies bound to C.albicans surface structures, the alternative pathway spontaneously, and the lectin pathway by mannan-specific lectins on the pathogen surface. As a consequence activated complement protein C3b binds to the pathogen’s surface, thus directing its opsonization and phagocytosis by recruited macrophages. For evading the complement system C. albicans recruits soluble host complement regulators to its surface, such as factor H and FHL1 as regulators of the alternative pathway, and C4b-binding protein, an inhibitor of the classical and the lectin pathway. Bound to the pathogen’s surface these recruited host regulators mediate inactivation of the central complement component C3. However, the molecular components involved in the evasion of C. albicans and the modulatory effects, which are mediated by fungal proteins via complement receptors on immune cells, particularly monocytes and macrophages, are still poorly understood. The project aims at elucidating the molecular principles of the interaction of C. albicans with macrophages and their response to the pathogen. Thereby the reaction of the immune cells to different stimuli provided by the pathogen will be of particular interest.
 
 
Ivanova, Lia

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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:

The impact of redox regulation on the stress response of Aspergillus fumigatus and its role in host-pathogen interaction

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Abstract: Recent studies have shown that reactive oxygen species (ROS), besides their involvement in protein and cell damage, also act as regulators for important cellular functions, mainly...
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... through reversible cysteine oxidation. Previously our group has shown (manuscript in preparation), that A. fumigatus experiences high levels of intracellular oxidative stress during adaptation to hypoxia or antifungal agents. It still remains unclear how ROS are distributed within the cell during these stress conditions and the physiological processes influenced by cysteine oxidation are not yet identified. The project will aim to establish genetically encoded fluorescent redox sensors, on the basis of molecules like HyPer-2 and roGFP2/Grx1-roGFP2, to allow observation of the flow and quantification of intracellular ROS under different stress conditions. Additionally, a quantitative redox proteomics method will be established in order to improve the identification and characterization of oxidative post translational modifications (PTMs). Combining the established iodoTMT method with the iTRAQ approach would also allow measuring changes in overall protein turnover. Later on, the main aim will be to observe intracellular redox changes in A. fumigatus during in vitro interaction with immune cells, allowing us to draw conclusions about the role of redox regulation in host-pathogen interactions.
 
 
Jo, Emeraldo

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FungiNet Student

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Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Research Group:
Infection Biology
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.
 
 
Institute/Dep.
Leibniz Institute of Photonic Technology (IPHT)
Dep. of Microscopy
PhD Project:

Development and application of high spatial resolution imaging for the characterization of intracellular infections

 
 
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.
 
 
Klapper, Martin

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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 Roles of Secondary Metabolites in Dictyostelium discoideum – Bacteria Interactions

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Abstract: This project will focus on both the identification of novel natural products as well as on the elucidation of their roles in eukaryote-prokaryote interactions. The social soil amoeba...
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... Dictyostelium discoideum will serve as the model eukaryote, whose secondary metabolome will be explored in a systematic fashion. D. discoideum is a voracious and ubiquitous predator of bacteria causing the depletion of large bacterial reservoirs. This puts both organisms under strong evolutionary selection pressure: consequently, the bacteria have evolved mechanisms to prevent grazing, and the amoeba must counteract or surmount these mechanisms in order to survive, for instance by the secretion of antibacterial metabolites. In particular, we are interested in a group of small molecules known as polyketides, of which only very few have been investigated. The structures and physiological roles of most of them, however, remain unknown. Specifically, we will examine their roles as signals or defense weapons in interspecies interactions when in contact with amoeba-pathogenic soil bacteria using a toolset of bioassays and methods that have been established in our lab. Emphasis will be put on the design of conditions that enable the expression of otherwise silent biosynthetic gene clusters of both the amoeba and bacteria. Thus, secondary metabolites will be accessible that would otherwise not be produced under standard laboratory conditions. Subsequent bioassay-guided fractionation of bioactive extracts from amoebal or bacterial cultures eventually allows for identification of natural products that orchestrate the coexistence and chemical warfare of the competitors in nature through their antibacterial, amoebicidal or cytotoxic properties. Thus, this project may give rise to new leads for anti-infective or anticancer drugs.
 
 
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

 
 
König (neé Franke), Annika

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publications »

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

Characterization of Candida albicans Ece1 membrane integration

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Abstract: Candida albicans is regarded as the most important of all medically relevant yeasts and is an extremely successful pathogen in humans. In contrast to most pathogenic fungi in humans...
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... such as Aspergillus fumigatus, Cryptococcus neoformans, or Histoplasma capsulatum, which are found in the environment, C. albicans belongs to the normal microflora of mucosal surfaces and are regarded as harmless commensals in most circumstances. In fact, most humans are probably colonized with these yeasts. An intact immune system and a balanced microbial flora are normally sufficient to protect the individual from Candida infections. However, certain critical events such as extensive antibacterial treatment or dysfunction of the immune system may enable these fungi to overgrow the microbial flora on mucosal surfaces. Using cellular, microbial, molecular and biochemical methods and C. albicans as model organisms, the goal of our research is to identify factors which fungal pathogens need to cause diseases. In addition to these efforts to increase our understanding of the basics of pathogenesis of fungal infections, we also seek to identify new biomarkers for diagnostic approaches and potential targets for antimycotic drug development. Under certain conditions, C. albicans is able to escape from macrophages by producing hyphal filaments. We discovered that the fungus produces the peptide toxin Ece1 during hyphal formation and during these interactions. We propose that Ece1 integrates into the host membrane to gain access to the host cytoplasm via pore formation. We have already shown that Ece1 plays an essential role during interaction with epithelial cells (unpublished data). In this project, the role of Ece1 integration will be studied in collaboration with groups working on optical high technology.
 
 
Krauße, Thomas

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ChemBioSys Student

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Institute/Dep.
Friedrich Schiller University Jena
Institute of Microbiology
Microbial Communication
 
 
Krespach, Mario

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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:

Communication between Streptomyces iranensis and Aspergillus – the streptomycete´s inducing principle?

 
 
Kreuzenbeck, Nina

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publications »

ChemBioSys 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:

Isolation, characterization and functional analysis of novel biomolecules from the mutualistic food fungus of fungus-growing termites

 
 
Kruse, Stefan

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publications »

JSMC Fellow

Email »

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.
 
 
Kurth, Colette

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ChemBioSys Student

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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:

Photoresponsive Modulation of a Freshwater Phytoplankton Community

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Abstract: Small molecule-mediated interactions of freshwater organisms are barely investigated with respect to their ecological impacts. In this project, the role of siderophores in structuring...
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... planktonic communities will be analyzed. Recent evidence suggests that some freshwater bacteria have acquired pathways for the biosynthesis of photoreactive Fe(III) ligands. Such compounds were before only known from marine bacteria, and they had been linked to the redox cycling of iron in the oceans. When exposed to sunlight, the iron complexes of these siderophores rapidly undergo an oxidative decomposition. At the same time, the coordinated ferric iron is reduced via ligand-to-metal charge transfer. The temporary increase of the Fe(II) concentration in the vicinity of the siderophore-producing bacteria promotes the assimilation of iron by associated algae. These planktonic consortia include many phototrophs, which are themselves not capable of siderophore-mediated iron uptake, but require large amounts of transient metal to support the fixation of carbon. Even though preliminary studies confirmed the growth-stimulating effects of photoreactive siderophores on marine microalgae and fueled the idea of a “carbon-for-iron” paradigm that would also be advantageous for the bacterial producers, many aspects of this mutualistic interaction are still poorly understood. In particular, we plan to resolve the discriminatory effects of photoreactive siderophores on a heterogeneous plankton community. Its members include both siderophore producers, such as cyanobacteria, and non-producers, among them many eukaryotic algae and protists. While the latter groups likely benefit from a facilitated access to iron, the former might encounter the opposite situation as they forfeit their advantage of endogeneous siderophore biosynthesis. It is therefore assumed that the bacterial release of photoreactive Fe(III) ligands induces a shift in the composition of a planktonic consortium away from prokaryotic siderophore producers. We will assess this impact, which may help us to delineate new strategies for the biological control of harmful algal blooms in rivers and lakes. Furthermore, we set out to clarify whether bacterial siderophore biosynthesis responds to signals from eukaryotic microalgae. The concomitant communication could rely on chemical molecules or, alternatively, on direct physical contact between the partners. Both scenarios will be probed by determining levels of bacterial gene expression in the presence and absence of diatoms or their cell culture extracts. We expect this experiment to provide fundamental insights into the evolution of natural product-mediated trans-kingdom interactions. Finally, we will validate the generalizability of mutualsitic iron sharing between heterotrophic bacteria and diatoms. For this purpose, we will analyze the genome sequences from selected freshwater bacteria, exploiting the predictability of microbial siderophore biosynthesis. The products of cryptic pathways will be isolated and characterized.
 
 
Lang, Stefan

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JSMC Fellow

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

Bioinformatics analysis of molecular mimicry in pathogenic fungi

 
 
Legros, Nadine

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Institute/Dep.
PhD Project:

TFP-TV8-AS12: Identifizierung und Charakterisierung der Glyko-Rezeptoren von viralen und bakteriellen Krankheitserregern

 
 
Leichnitz, Daniel

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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:

Exploitation and total synthesis of new microbial sphingolipid-type signaling molecules

 
 
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

 
 
Li, Qianqian

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JSMC Fellow

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

Chemical communication between bacteria in iron-rich lake aggregates

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Abstract: Iron-rich pelagic aggregates have been termed “iron snow” which are different from the more organically rich snow-like aggregates known from marine and freshwater environment. The...
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... pelagic aggregates formed in the water column through adsorption of inorganic and organic matter and colonization of motile microorganisms contribute substantially to the energy transfer from the photic zone to deeper water layers. Pelagic aggregates are thus local hot spots for microbial interactions by direct cell contact and feeding, as well as the action of diffusive signals. Chemical signaling molecules have been suspected to regulate bacterial colonization, coordinate group behavior, in addition to antagonistic activities within pelagic aggregates. Comparative metabolomics was be used to identify metabolites produced by microorganisms grown in co-culture by comparison with those of single-strain cultures. In this study, we found Ferrovum sp. (iron oxidizer) was always with Acidiphilium sp.(iron reducer) and that made more difficult to isolate the pure isolate of Ferrovum sp. If Acidiphilium sp. was added to the medium with Ferrovum sp., the growth of Ferrovum sp. would be promoted. Firstly, pure strain of Ferrorvum spp should be purified and isolated with conventional method of streaking plate in artificial pilot-plant water( APPW) medium. After that, supernatant exchange experiment was to detect extracellular chemical mediators produces by the isolates.
 
 
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.
 
 
Mamerow, Svenja Katharina

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Institute/Dep.
PhD Project:

Development and Evaluation of Influenza A Virus Live Attenuated Vaccines in Swine

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

Characterizing innate immune cell activation by fungal pathogens using Live Cell Imaging

 
 
Marx, Carina

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Institute/Dep.
PhD Project:

Identifizierung molekularer Targets potentieller Antibiotika

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

Using fluorescent Enterococcus mundtii to study the variation in its gene expression, spatially and temporally, in the gut of Spodoptera littoralis larva

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Abstract: Insects harbor a plethora of microorganisms within their gut, as their normal flora. They are not only non-pathogenic to them, but also have roles to play in the insect growth,...
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... development and immunity. There lies a complex interaction within the microflora and also, between the host and the microorganisms. This leads to variations in the microbial population with the development of the insect. Some get eliminated, some are added, whereas, some dominate throughout the insect life cycle. The gut microbiota of Spodoptera littoralis, a Lepidopteran insect of family Noctuidae, has been elucidated. The core community consists of Enterococci, Lactobacilli and Clostridia. The selection of one bacterial species over the other is quite evident throughout the life-cycle. The community varies with the stages of development of the larva, and spatially within the gut. By the time the larva reaches the 5th instar stage, Enterococcus mundtii and Clostridia sp persists and dominates. The class IIa antimicrobial peptide- mundticin KS, produced by Enterococcus mundtii, acts against the invading bacteria, and exercises its predominance. This way, they help preserve the host gut microbiota, reduce infection in the host and enhance its health. A method of fluorophore-labelling of Enterococcus mundtii has been developed to show that it is the persistent and metabolically active species in the gut microbiota, which in turn, intrigues us to find out the importance of this symbiotic species. Thus, the aim of my project will be to isolate the fluorescent Enterococcus mundtii from various regions of the larval gut, across its developmental stages, and study the variation in their gene expression. The Next generation method of RNAseq will be used to sequence the transcriptome. Thus, on analyzing the transcriptome of Enterococcus mundtii over the stages of Spodoptera littoralis larval development, we might conclude its specific role as a symbiont and its importance as a dominating gut microbiota. Once successful, the approach can be extended to other relevant gut bacteria and their role as symbionts, like, Clostridia sp, which dominate the gut till the later stages of development, even in depleting iron conditions.
 
 
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.
 
 
Meyer, Nils

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ChemBioSys Student

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

Algicidal Bacteria in Plankton Communities: Resistance, Lysis and Heterotrophy

 
 
Mohr, Jan Frieder

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ChemBioSys Student

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

Metallophores as mediators for metal cycling: Development of libraries for metal ion buffering and as redox carriers as well as profiling of metallophores

 
 
Müller, Tina

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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:

Host defense mechanisms against pathogens mediated by sphingolipids

 
 
Munser, Anne-Sophie

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Institute/Dep.
Fraunhofer Institute for Applied Optics and Precision Engineering, Jena
 
 
Normann, Nicole

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Institute/Dep.
PhD Project:

Protein markers for pathogen detection and risk stratification in patients with a suspected bacterial infection

 
 
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-Institut
Junior Research Group Evolution of Microbial Interactions
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
 
 
Oago Onchuru, Thomas

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JSMC Fellow

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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

 
 
Oetama, Vincensius

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

Chlorophyll degradation in Spodoptera littoralis

 
 
Papanikolopoulou, Lydia

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JSMC Fellow

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

Mechanisms of positive allelopathy in phytoplankton

 
 
Peña Ortiz, Luis Alberto

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publications »

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Institute/Dep.
Friedrich Schiller University Jena
Carl Zeiss Junior Research Group Synthetic Microbiology
PhD Project:

Identification and biotechnological assembly of cryptic cofactors

 
 
Pezzini, Francesco

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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:

Epigenetic control of secondary metabolism in filamentous fungi (Bioinformatic analysis and modeling)

Abstract: Secondary metabolites (SM) (antibiotics, toxins, etc.) are pharmaceutically important substances involved in microbial communications. The PhD project will be devoted to detection of...
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... epigenetic marks for regulation of SM cluster genes. This will include the work with NGS data (e.g., merging nucleosome and transciptome data), analysis of nucleosome positioning in genes and promoters of active and inactive SM clusters, application of comparative analysis and systems biology approaches
 
 
Pietschmann, Sebastian

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

Microbial succession in heavy-metal contaminated soils during in-situ phytoremediation

 
 
Pötschner, Jessica

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

Lipid rafts in fungi

 
 
Pourmasoumi, Farzaneh

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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
Biosynthetic Design of Natural Products
PhD Project:

Directed evolution of antibiotic producers

 
 
Preußger, Daniel

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JSMC Fellow

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

Molecular mechanisms of antifungal resistance and therapeutic strategies to manage infections with triazole

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Abstract: The PhD project in the group of Prof. Dr. Brakhage (Department of Molecular and Applied Microbiology) studies the human pathogenic fungus Aspergillus fumigatus and consists of two...
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... parts. One part belongs to the FINAR (Management of Fungal Infections in the Era of Emerging Azole Resistance) effort and focuses on the emerging problem of azole antifungal resistance in filamentous fungi. This topic is currently very important as more and more azole-resistant fungal isolates are recovered from patients, but there are very few treatment alternatives. The starting point for this project are natural products which show a synergistic effect when applied together with azole antifungals. These compounds could be the first step towards drugs that preserve the activity of azole antifungals in spite of the emerging resistances. The aim of this project is to characterize the effect and the mechanism of action of these compounds using –omics methods and a Knock-Out-mutant library of A. fumigatus and to possibly find new resistance mechanisms. The second part of the PhD project is aimed at DHN-melanin, a virulence factor of A. fumigatus. DHN-melanin is located on the conidial surface and protects the conidia for example against UV radiation and, during infection, from host defense mechanisms. It can withstand even harsh conditions easily. This project aims to discover how DHN-melanin is degraded by the fungus using proteomic and transcriptomic approaches.
 
 
Raguž, Luka

publications »

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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:

Molecular synthetic approaches towards natural sphingoid base-type signaling molecules

Abstract: Sphingoid bases and sphingolipids are essential multifunctional cellular compounds, which serve not only as integral components of cell membranes, but also as essential regulatory...
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... signals for fundamental cellular processes. They were first thought to exist exclusively in eukaryotes, but have now been repeatedly identified and isolated from important bacterial and viral sources. Despite being abundant signaling molecules, the biological function of many sphingolipid derivatives remains elusive. Prominent examples of fungal origin are sphingofungins and myriocin (ISP-1), which exhibit antifungal activity in the picomolar to nanomolar range. Their discovery has led to the development of many pharmaceutical drug leads (e.g. FTY720 and safingol. But the intrinsic biological role of sphingofungins is unknown until to date. In another study bacterial sulfonolipids, such as RIF-1 and RIF-2, regulate an onset of development in one of the closest living relatives of animals, the choanoflagellate Salpingoeca rosetta. A structural analog IOR-1 inhibits partially the activity of RIF molecules. Due to their intrinsic biological function of these types of molecules, this research project will focus on efficient and new synthetic strategies towards of rare microbial sphingoid base-type signaling molecules to allow their detailed functional analysis.
 
 
Ramachandra, Shruthi

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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. Microbial Pathogenicity Mechanisms
PhD Project:

Host pathogen interactions of human-pathogenic yeast

 
 
Raszkowski, Daniel

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JSMC Fellow

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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.
 
 
Rischer, Maja

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publications »

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:

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

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Abstract: Metamorphosis in marine invertebrate larvae is often an environmentally dependent process and larvae of many marine invertebrates use biofilm components as cues to appropriate...
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... settlement sites (habitats). In many phyla species of the bacterial genus Pseudoalteromonas induce larval settlement and metamorphosis, but despite century long intensive research, we still know very little about the bacterial ligands that stimulate larval settlement and the cellular basis of their detection by larvae.
We have chosen the colonial marine hydroid Hydractinia echinata as model organism, which grows on the shells inhabited by hermit crabs. Here, it is long known that the metamorphosis from free-swimming larvae to the sessile polyp is particularly stimulated by bacteria of the genus Pseudoalteromonas. This project will first focus on the characterization of the specific bacterial morphogenic factor from a highly inductive Pseudoalteromonas strain using a combination of various methods (molecular biology, genome analysis, proteomics, and imaging).
Biofilm and invertebrate settlement are part of the so-called ‘biofouling community’ that inhabit artificial surfaces and cause major economic losses around the globe. Analysing the settlement mechanisms might lead to new strategies to prevent biofouling, and decrease the current use of environmentally harmful and toxic antifouling agents.
As a second project we will analyse the chemical potential of microbes associated with H. echinata. It is known that Cnidara cultures are sensible to infection and parasitic infestation when they have lost important microbial commensals and symbionts. We hypothesize that microbial commensals contribute by secretion of antimicrobial compounds to the host defense and therefore represent a very promising source of biologically important natural products. We have established a collection of wildtype bacteria and fungi from the tissue surface of healthy polyps, which are currently under investigation using bioassay-guided fractionation and other dereplication methods. Isolation and structure identification of antimicrobial secondary metabolites is performed by using different analytical techniques like HPLC, NMR, UV-VIS and others. Based on sequenced genomes we want to investigate biosynthetic pathways of the characterized molecules and predict unknown secondary metabolite clusters through genome mining.
 
 
Röcker, Marie

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publications »

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:

Identification of immunogenic components of Aspergillus fumigatus for vaccine development

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Abstract: Aspergillus fumigatus is the most important air-borne fungal pathogen. In recent years, it became evident that certain unknown components of A. fumigatus apparently lead to protection...
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... against invasive aspergillosis in a mouse infection model. Until now, it remains to be shown whether the protection is due to a B cell response or rather T cell response. Furthermore, the components of A. fumigatus triggering this response have not been identified. The proposed project will investigate, which morphotypes (spore, mycelium) promote an immune response and which protein antigens contribute to this host reaction. The immunological properties of selected protein antigens will be further investigated in murine models of Invasive Aspergillosis (B-cells, T-cells). In collaboration with the Charite´ (Berlin) the T-cell response against Invasive Aspergillosis of Cystic Fibrosis patients will be characterized.
 
 
Rudolphi, Sven

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FungiNet Student

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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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JSMC Fellow

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Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Network Modeling
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.
 
 
Schaarschmidt, Barbara

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FungiNet Student

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

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ChemBioSys Student

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

Identification of Novel Secondary Metabolites with Roles in Interactions Between Chlamydomonas reinhardtii and Other Microorganisms

 
 
Scheven, Mareike

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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:

Novel molecular mechanisms of iron sensing and homeostasis in Aspergillus fumigatus

 
 
Schmidt, Franziska

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Email »

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

Virulence of Aspergillus fumigatus and Host-Pathogen Interactions

 
 
Schoeler, Hanno

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publications »

FungiNet 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:

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.
 
 
Schumann, Martin

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JSMC Fellow

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

Microbial origin of banded iron formations

 
 
Schürmann, Michaela

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Email »

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

Antimicrobial Effect of Nano-Rough Titanium surfaces: Reduction of Microbial Adhesion and Mechanisms of Reduction

 
 
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.
 
 
Shopova, Iordana

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FungiNet 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:

Communication between human polymorphonuclear granulocytes and Aspergillus fumigatus

 
 
Institute/Dep.
Friedrich Schiller University Jena
Dept. of Bioinformatics
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Research Group: Systems Biology / Bioinformatics
PhD Project:

Bioinformatic Analysis of alternative splicing in human pathogenic fungi

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Abstract: Alternative splicing (AS) processes can be found in a wide range of species. It is well studied in higher organisms but little is known about its regulation and effects in fungal...
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... species. This PhD project deals with the bioinformatics analysis of RNA-Seq data in order to identify AS events in human-pathogenic fungi and to predict the effect of AS on the infection process. Therefore, different tools for mapping of RNA-Seq data and detecting significantly alternatively spliced genes are used. A workflow for the reliable prediction of AS events in fungi will be developed. Identified AS events are the basis for multi-species comparisons which will gain new insights into the evolutionary connection of AS in fungi. Furthermore, it is of interest to discover the consequences of AS concerning their protein structure.
 
 
Siscar, Sofia Lewin

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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-
Dept. Microbial Pathogenicity Mechanisms
PhD Project:

Host adaptation, avirulence and antivirulence genes of Candida glabrata

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Abstract: Microbial evolution and adaptation to specific niches, such as the human body, are driven by genetic mutations and alterations including gain of new genes, modification of existing...
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... genes, but also loss of genes detrimental for survival in a particular niche or for a particular life style. For example, Yersinia pestis, a highly pathogenic micro-organism, has lost multiple genes and has a smaller genome than less pathogenic species; and M. leprae, the causative agent of leprosy, shows an extreme gene reduction concomitant with a loss of many metabolic functions. Candida glabrata is a commensal member of the microbiome in the majority of humans. However, it is also common opportunistic pathogen causing superficial to life-threatening infections under certain predisposing conditions. Of note, C. glabrata is phylogenetically more closely related to the baker’s yeast Saccharomyces cerevisiae than to other important pathogens such as C. albicans, and has developed pathogenicity strategies during host adaptation which differ markedly from the latter. One remarkable attribute of C. glabrata, in contrast to C. albicans, is the loss of distinct metabolic pathways resulting in several auxotrophies, which allow fungal cells to sense these molecules in the host to initiate a response suitable for fitness, survival and infection. Another example for genetic loss are secreted proteins of C. albicans, which elicit immune response in the host. C. glabrata, in contrast, lacks many of these proteins, and hence immunogenic signals and in general elicits a much lower immune response in ex vivo and in vivo models. Since C. glabrata has evolved pathogenicity mechanisms as an opportunistic pathogen, which is phylogenetically closely related to the baker’s yeast Saccharomyces cerevisiae, we aim to elucidate which particular genes of C. glabrata have diverged (possible avirulence genes, which would elicit a host response in the original form) or have been lost (potential antivirulence genes, which would reduce pathogenesis by their function) during host adaptation. This will increase our understanding of the past evolution of metabolism and interspecies molecular signaling between pathogens and their host. Characterizing these avirulence and antivirulence genes may help to identify new biomarkers and potential targets for antimycotic drug development. Importantly, the selection of the genes to be investigated in this project will be based on in silico analyses of existing transcriptional profiles, which have been obtained during simulated ex vivo infection of a whole-blood model. Additionally, this selection will also be based on in silico analysis of the evolution of C. glabrata and its related species, in cooperation with international collaboration partners.
 
 
Sreekantapuram, Venkata Naga Sravya

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Institute/Dep.
 
 
Stanford, Felicia

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JSMC Fellow

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

Adaptive traits as mediators of stress response and virulence in Lichtheimia

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

Antimicrobial Effect of Nano-Rough Titanium Surfaces: Reduction of Microbial Adhesion and Mechanisms of Reduction

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

Application of Orbitrap-GC/MS to metabolomics research

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

Cultivation Strategies for the Characterization of Secondary Metabolite Production in Anaerobic Bacteria

 
 
Tauber, James

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ChemBioSys Student

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

Role and regulation of secondary metabolites by basidiomycetes during inter-organismal interactions

 
 
Teh, Beng Soon

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publications »

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.
 
 
Thürich, Johannes

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publications »

ChemBioSys Student

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

Isolation and Characterization of Novel Biomolecules from Fungi Establishing Mutualistic or Pathogenic Interactions with Roots of Arabidopsis and Nicotiana Species

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Abstract: The goal of my project is to study the interaction of Arabidopsis thaliana and Nicotiana attenuata with root-colonizing fungi. These fungi, i.e. Piriformospora indica, Mortierella...
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... hyalina, Alternaria brassicae and Verticillium dahliae, exudate compounds which induce rapid cytosolic calcium elevation in roots. (Fig 1.) The Ca2+ signal is important for the downstream responses of plants such as gene activation or release of antifungal compounds. I will identify and characterize these unknown biomolecules and the in planta counterparts. Calcium measurement, next generation sequencing, mass spectrometry, gene expression studies and bio assays will help me to get new insights into the plant-microbial signaling.
 
 
Timme, Sandra

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publications »

FungiNet 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:

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

 
 
Töpfer, Natalie

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publications »

JSMC Fellow

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Institute/Dep.
Center of Sepsis Control and Care (CSCC)
PhD Project:

Characterization of pathogen-leukocyte interaction by means of Raman spectroscopy

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Abstract: Worldwide a third of all sepsis patients die from their condition. This systemic reaction can occur after infection with pathogens for example after surgery. In this uncontrolled...
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... hyper-inflammatory response leukocytes play an important role. Especially neutrophils, which are the most abundant representative of the immune system, are able to engulf pathogens and oppose them via phagocytosis. The pathogen is trapped intracellularly where it can be digested by granular enzymes and antimicrobial peptides. In a few cases, neutrophil extracellular traps (NETs) are produced to bind the pathogens with fibers composed of DNA and globular proteins. Macrophages and their progenitor cells, monocytes, are also able to phagocytize microbes and - like neutrophils - are important producers of inflammatory cytokines.
In the course of this project the infection mechanisms of the opportunistic pathogenic fungi Candida albicans an Aspergillus fumigatus will be investigated. Both pathogens are known to have polymorph phenotypes and cause localized, but also systemic infections. Systemic candidiasis and invasive aspergillosis are prominent in immunocompromised patients, like patients undergoing organ or stem cell transplantation, chemotherapy or AIDS. Raman spectroscopy will be used to study the interaction between neutrophils / monocytes and C. albicans/A. fumigatus. Leukocytes and pathogens will be visualized with false color Raman images before and after infection. The molecular information of the Raman spectra will be extracted
and compared to biochemical information gained through biological methods. Furthermore, this project could give insight into the characteristic differences between the pathogens that are to be phagocytized and which are not.
 
 
Tovar, Miguel

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publications »

JSMC Fellow

Email »

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

 
 
Ullah, Chhana

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publications »

JSMC Fellow

Email »

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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publications »

JSMC Fellow

Email »

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.
 
 
Vivas, Wolfgang

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publications »

JSMC Fellow

Email »

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

Modulation of Dendritic Cell Function by the fungal Quorum Sensing Molecule Farnesol

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Abstract: Quorum Sensing is a major mechanism of inter-microbial communication mediated by molecules that are released from growing microorganisms and accumulate in relation to microbial...
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... replication. Farnesol – the first identified fungal quorum sensing molecule – mediates the response of Candida albicans to growing population density and controls filamentation of C. albicans which is a major virulence trait. Beside species-specific effects on C. albicans, farnesol can exert effects on other microbes and is therefore a prototype mediator of inter- and intraspecies microbial communication. In previous work we have investigated the impact of farnesol on innate immune cells. For this, we used several infection models with primary human monocytes, monocytes-derived dendritic cells, and neutrophilic granulocytes that are established in our lab. Farnesol was able to induce activation of neutrophils and monocytes and triggered the release of pro-inflammatory cytokines. In contrast, farnesol impaired differentiation of monocytes into dendritic cells (DC) by modulating the phenotype, cytokine release and migrational behavior during differentiation. These modulatory effects resulted in severely impaired induction of antifungal activity in DC. In the proposed project, we will build from this work and try to elucidate the molecular basis of farnesol mediated DC differentiation, maturation and functionality. We will use of state of the art microbiological and immunological tools, primarily working with monocytes-derived DC. The project is built on several collaborations, including Prof. Dr. Marc Thilo Figge.
 
 
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

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Abstract: The saprophytic filamentous fungus Aspergillus fumigatus stays in focus of the current clinical research causing opportunistic infections in immunosuppressed patients, which can lead to...
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... life-threatening invasive aspergillosis. Moreover, the fungus is found in a wide variety of habitats including soil and decaying organic matter. An explanation for its ability to adapt to such diverse environments could be due to the production of a broad range of secondary metabolites (SM) with a wide spectrum of biological activity. Genome analyses of A. fumigatus have revealed a large number of putative SM biosynthesis genes commonly found in specific SM gene clusters. Despite this, only a few SM gene clusters are activated under standard laboratory conditions, making it difficult to assign SM to their corresponding SM gene clusters. One approach to identify silent gene clusters uses the regulation of gene expression via histone modifying enzymes. Especially with histone acetylation by histone acetyltransferases (HATs), which are generally involved in gene activation. Previous studies in Aspergillus nidulans have demonstrated that HATs play an important role in secondary metabolism (Nützmann et al., 2011. Proc Natl Acad Sci USA; 108(34):14282-7), but little is known about the pathogenic fungus A. fumigatus. There are approximately 50 putative acetyltransferase-encoding genes in A. fumigatus and current work of this PhD project aims at creating a knock-out (KO) library of these HATs. The library will be used in high-throughput screenings to understand the global function of HATs and in particular their role in pathogenicity, microbial interaction and regulation of SM gene clusters.
 
 
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.
 
 
Wilde, Julia

publications »

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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publications »

JSMC Fellow

Email »

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.
 
 
Wirgenings né Brensing, Marino

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

Total Synthesis of Copepodamides and SAR Studies of Analogues

 
 
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

 
 
Wolff, Christian

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JSMC Fellow

Institute/Dep.
PhD Project:

An integrated functional genomics approach to unravel the mode-of-action of novel antiinfective compounds

 
 
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.