|CCL 16.10.26 PhD student, Mol. simulation & modeling, Univ. Duesseldorf: Overcoming lantibiotics resistance in bacterial pathogens|
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To: jobs at ccl.net
Date: Wed Oct 26 03:58:55 2016
Subject: 16.10.26 PhD student, Mol. simulation & modeling, Univ. Duesseldorf: Overcoming lantibiotics resistance in bacterial pathogens
Applications are invited for a PhD student position in the Computational Pharmaceutical Chemistry & Molecular Bioinformatics group (Prof. Dr. Holger Gohlke; http://cpclab.uni-duesseldorf.de) at the Heinrich Heine University Dsseldorf, Germany. Topic: Overcoming lantibiotics resistance in bacterial pathogens: Nisin as a model system Lantibiotics are antimicrobial peptides, are produced by Gram-positive bacteria, and show bactericidal effects against other bacteria in the low nanomolar range. Due to their high selectivity and stability, lantibiotics are considered valuable future anti-infectives. The best studied lantibiotic nisin, produced by the lactic acid bacterium L. lactis, has been used for more than 50 years as an additive in food. In various human pathogenic bacterial strains (e.g. S. aureus and S. agalactiae), which do not produce nisin itself, a natural immunity to nisin was observed, which was attributed to the nisin resistance protein (NSR). NSR is a so-called C-terminus processive peptidase that cleaves the last six amino acids of nisin, whereby the effectiveness of nisin is reduced by 100 to 1000 times. By a drug-induced inhibition of NSR, the nisin resistance of these strains could be overcome, thus making anti-infective therapy with nisin possible. The aim of this project is the identification of small molecule inhibitors of NSR. As a model system NSR was chosen from S. agilactiae (SaNSR). By integrative modeling, mutagenesis studies, and genetic engineering of nisin variants, a model of the SaNSR/nisin complex has been recently generated, based on the first three-dimensional structure of a nisin resistance protein (DOI: 10.1038/srep18679). The work will be performed within the newly funded DFG Graduate School GRK 2158 Natural products and analogs against therapy-resistant tumors and microorganisms: New lead structures and mechanisms of action (http://www.grk2158.hhu.de/en.html). The PhD student will perform molecular simulation and modeling studies in the Gohlke lab and will furthermore work closely together with scientists of the lab of Dr. Sander Smits for experimentally validating the established models and predictions. Requirements: The ideal candidate will have a record of excellence and a strong background in computational biochemistry/chemistry or structural bioinformatics, a high interest in working in an interdisciplinary collaboration, and profound knowledge in state-of-the-art molecular dynamics simulations (Amber) software and molecular modeling. Detailed information about living and studying in Dsseldorf is provided here: http://www.uni-duesseldorf.de/home/leben-in-duesseldorf.html
Applicants should submit applications (a one-page letter of motivation _why_ they are interested in the respective project and _how_ they can contribute to the projects success, a current CV, and contact data of three references) by email to gohlke!^!uni-duesseldorf.de . Please provide all documents as one PDF file and specify for which position you are applying.NOTE THAT E-MAIL ADDRESSES HAVE BEEN MODIFIED!!!
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