Doctoral Researchers

 
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.

PDF »

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

Regulation of antibody production and functionality during Candida albicans infections

PDF »

Abstract: Candida albicans is a benign member of the human microbiota, but can become a lethal pathogen in immunocompromised hosts. As it plays a substantial and increasing role in nosocomial...
more
... infections, and resistances to the few available antifungal agents arise, alternative preventive or curative approaches are highly desirable. While the role of neutrophils, myeloid cells and T cells in response to acute C. albicans infection has been intensely studied, the role of B cells and antibodies is much less well understood although approaches for vaccination of at-risk patients are already undertaken. In previous studies, we found that purified B cells stimulated ex vivo with C. albicans showed increased production of IgG1 and IL-6 in a TLR/MyD88 dependent way. The present PhD project aims at deciphering the regulation of antibody production of B cells by C. albicans itself as well as by soluble host immune factors. Also, we wish to understand how certain secreted aspartic proteinases (SAPs) of C. albicans may interfere with the functionality of these antibodies as a mechanism for either host adaptation or immune escape. Furthermore, we will analyse how soluble serum immune factors affect the human B cell response to C. albicans components, in order to better understand how patients may react to vaccination responses in different settings.
 
 
Wilde, Julia

publications »

JSMC Fellow

Email »

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

cv + contact data »

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

PDF »

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....
more
... 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

cv + contact data »

publications »

Email »

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

cv + contact data »

publications »

JSMC Fellow

Email »

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

Volatilome of Schizophyllum commune

 
 
Wolff, Christian

publications »

JSMC Fellow

Institute/Dep.
PhD Project:

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