Doctoral Researchers

 
Wadke, Namita

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JSMC Fellow

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

Biochemistry and ecology of stilbene detoxification by fungal plant pathogens

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

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JSMC Fellow

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

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

 
 
Winkler, Thomas

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JSMC Fellow

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

Semisynthetic Nosiheptide Derivatives Enabling an Improved Selectivity Profile

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

 
 
Wissuwa, Bianka

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

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

 
 
Wolff, Christian

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Institute/Dep.
PhD Project:

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