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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; 
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 ( 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:
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!^! . 
Please provide all documents as one PDF file and specify for which 
position you are applying.
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Modified: Wed Oct 26 07:58:56 2016 GMT
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