PhD position: Combinatorial biosynthesis of nonribosomal peptide antibiotics

The Leibniz Institute for Natural Product Research and Infection Biology – Hans Knöll Institute – in cooperation with the Friedrich Schiller University, the University Hospital Jena and the Max Planck Institute for Chemical Ecology are offering an international graduate training programme. The International Leibniz Research School (ILRS Jena) gives doctoral researchers the possibility to prepare for their PhD exam in an ambitious program providing excellent research conditions. We invite applications for a Doctoral Researcher Position (Ref.No. ILRS_08/2016): Combinatorial biosynthesis of nonribosomal peptide antibiotics

Nonribosomal peptide synthetases (NRPSs) produce numerous biologically active peptides, including potent antibiotics, and are suitable for biosynthetic engineering due to their modular molecular architecture. NRPS modules typically consist of adenylation (A), condensation (C), and thiolation (T) domains organized in huge multimodular proteins like beads on a string. These modules elongate the nascent peptide chain one amino acid at a time. Several NRPS engineering approaches have been proposed in the past that suffer from various shortcomings. Binding pocket mutagenesis can be laborious and insufficient for larger changes in specificity and module or domain swaps can disrupt interdomain contacts.

In this project, a streamlined process for combinatorial biosynthesis of nonribosomal peptides will be developed based on ‘subdomain swapping’. These subdomains encompass known specificity determining factors of the A domain and are short enough for cost-effective gene synthesis. When subdomains are retrieved from sequence databases and synthesized, subdomain swapping can potentially produce a much larger number of module permutations than previous approaches. Strategies for combinatorial subdomain swapping will be developed to change multiple residues in one nonribosomal peptide. Using a novel microfluidics platform for antibiotic discovery, the resulting NRPS libraries will be screened for production of antibiotic peptides in collaboration with another PhD student. Directed evolution will be applied to overcome potential activity losses and to optimize peptide production. If successful, subdomain screening may accelerate the biosynthetic engineering of peptide natural products and contribute to the development of tailor-made drugs.

We expect:
- a Master’s degree (or equivalent allowing you to pursue a PhD degree) in Natural or Life Sciences. Research at ILRS is centred around “Microbial and Biomolecular Interactions”. Candidates about to earn their degree are welcome to apply.
- high motivation to join one of the research areas of ILRS
- creativity and interest in shaping your own thesis project
- an integrative and cooperative personality with enthusiasm for actively participating in our lively community
- very good communication skills in English
- laboratory experience in molecular biology or microbiology is desired

We offer:
- a top-level research environment
- efficient supervision by a team of advisors
- a comprehensive mentoring programme
- courses in state-of-the-art technologies and soft skills
- strong communication and interaction between the involved institutions
- Jena – City of Science: innovative business activities, successful scientific centres and a vibrant cultural scene around the famous Friedrich Schiller University

The three-year Doctoral Researcher position is available starting from January 2017. The position will be financially supported according to TV-L (salary agreement for public service employees). HKI is an equal opportunity employer.

Further information
Dr. Hajo Kries, PI, [Email Address Removed]
Dr. Christine Vogler, ILRS -Coordinator, [Email Address Removed]

Applications
The application process is handled exclusively online. Please acquaint yourself with the scientific projects offered on our website. Please note that you can choose up to 3 projects of interest in your application. It is only necessary to fill in the application form for your first preference of projects; the other two projects can be selected in the application form.

https://orthos.hki-jena.de/jobs/Doctoral-Researcher-mf-biochemistry-microbiology-eng-j41.html

Deadline for application: Oct 23, 2016.
Successful applicants will be invited to attend a recruitment meeting in Jena (envisaged date: Dec 14-15, 2016).