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Synthetic Biology of Multimodular, Nonribosomal Peptide Biosynthesis

The Jena School for Microbial Communication (JSMC) is funded by the German Excellence Initiative. JSMC is an ambitious Graduate School with over 150 doctoral researchers who are educated in a structured, interdisciplinary training program based on top-level fundamental research. It conceptually combines different research areas to a comprehensive picture of microbial communication (www.jsmc.uni-jena.de). Institutes at five facilities of the Friedrich Schiller University Jena, six non-university research institutes as well as 12 partner companies are participating in this cutting-edge research and training program.
The Graduate School of Excellence ‘JSMC’ invites applications for a
Doctoral Researcher Position TV-L E13 65% (Ref. No. HKI 27/2015)
to conduct research on the project
Synthetic Biology of Multimodular, Nonribosomal Peptide Biosynthesis
Background: Nonribosomally synthesized peptides (NRPs) represent one of the major groups of microbial bioactive natural products. A number of NRPs are highly potent molecules, which are currently in clinically use as antibiotics (vancomycin or daptomycin) or immunosuppressants (cyclosporin). Some NRPs (e.g. hormaomycin) are involved in bacterial interactions and chemical communication. NRPs often contain nonproteinogenic amino acids that are difficult to synthesize chemically. The biosynthesis of nonribosomal peptides is governed by gigantic, multimodular enzyme systems called nonribosomal peptide synthetases (NRPS). They resemble molecular “assembly lines” where each module minimally consists of a three domain set: an adenylation domain that recognizes and activates the building block (amino acid) to be incorporated, a condensation domain that forms the new peptide bond and a thiolation domain that carries the growing peptide chain. For quite some time the “holy grail” in natural product biochemistry has been to generate novel “unnatural products” by freely recombining these modules in a “Lego-like” fashion. This methodology would grant innovative access to improved compounds which might, for instance, display less side effects or enhanced stability in clinical settings. Despite some successful engineering attempts in the past, general “rules” for successful NRPS recombination are still rudimentary.
Objectives: The engineering of microbial NRPS systems to produce lead drug candidates with antibiotic activity against the causative agents for tuberculosis and malaria will be conducted in order to gain access to novel molecules with improved pharmacokinetic properties (reduced toxicity, improved bioavailability). General rules for successful NRPS engineering will be formulated.
Methodology: Modern synthetic biology methods will be used to generate libraries of novel NRPS assembly lines in vivo. Case studies will be performed in vitro using purified fusion proteins. State-of-the-art mass spectrometric methods will be employed to monitor product formation.
We expect:
  • A Master’s degree (or equivalent) in Life Sciences (e.g. Biology, Biochemistry, Biotechnology or related). Candidates about to earn their degree are welcome to apply.
  • A strong theoretical background in molecular genetics and  biochemistry or biological chemistry
  • Practical experience in synthetic biology (e.g. tranformation-associated recombination in yeast, Gibson-assembly) or directed evolution/protein engineering. Practical experience in metabolite extraction and analysis of natural products (LC-MS) is beneficial.
  • High motivation and interest to join one of the interdisciplinary research areas of JSMC
  • Creativity and interest to shape your own thesis project
  • A flexible and cooperative personality with enthusiasm for actively participating in the lively JSMC Community
  • very good communication skills in English (instruction language at JSMC)
We offer:
  • Modern lab equipment including high resolution mass spectrometric devices
  • A multi-disciplinary environment
  • A highly communicative atmosphere within a scientific network providing top-level research facilities
  • A doctoral researcher position (TV-L E13, 65%) with guaranteed funding for one and a half years based on the regulations of the German Research Foundation as well as generous research funding with the possibility of funding extension for completion of the PhD project
  • A comprehensive mentoring program with supervision by a team of advisors
  • A top-level PhD training program with courses in state-of-the-art research technologies and soft skills
  • Jena – City of Science: a young and lively town with dynamic business activities, successful scientific centers of innovation and a vibrant cultural scene around the famous Friedrich Schiller University
Friedrich Schiller University Jena is an equal opportunity employer. Disabled persons with comparable qualifications receive preferential status.

The application procedure takes place exclusively online via the JSMC website:
Please acquaint yourself with the open PhD projects and the application process described on this website.

Selected applicants will be invited to the JSMC Recruitment Meeting in Jena, Germany, in January 2016. Awarding decisions will be made shortly thereafter, allowing the projects to start immediately.

Application deadline: November 17th, 2015
How to apply:
The application procedure takes place exclusively online via the JSMC website:
Kontakt für Bewerbungen
Bitte beziehen Sie sich bei Ihrer Bewerbung auf jobvector und geben Sie die folgende Referenznummer an: Ref. No. HKI 27/2015

Über Jena School for Microbial Communication

The Jena School for Microbial Communication (JSMC) is funded by the German Excellence Initiative . It conceptionally combines different research areas (microbial communities, interactions with plant, animal and human hosts and environmental interactions) to a comprehensive picture of microbial communication (www.jsmc.uni-jena.de). JSMC is an ambitious Graduate School currently hosting over...

Mehr über die Jena School for Microbial Communication

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