Deadline: March 16, 2012
Nosiheptide belongs to the thiopeptide natural products and is a highly potent antibiotic but chronically 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.
In order to uncover highly active compounds with a selective mode of action, this project will explore semisynthetic derivatization of nosiheptide [7]. Its scaffold will be evolved by degradation and chemical synthesis using both established[3,4] and new techniques to yield a focused library of
compounds. The library will be profiled in assays for bacterial growth, protein biosynthesis inhibition and proteasome modulation. In a second part of the project, TipAL induction will be studied,[8] in order to uncover and track modulators of each of the specific activities of nosiheptide in bacteria and
eukaryote.
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 inter- disciplinary training will qualify the candidate for advanced research and leadership positions in
Chemical Biology and Drug Developmen.
Application Guidelines
For the first stage of the application procedure (submission of the “Statement of Interest” form):
- Please acquaint yourself with the open projects being offered within the 9th JSMC Recruitment Call
- Download and complete the “Statement of Interest” form.
- Save the completed “Statement of Interest” on your computer (filename: JSMC–.PDF)
- Submit this pdf document as an email attachment to apply-jsmc(at)uni-jena.de
Please note:
- Applications can ONLY be considered if the COMPLETED “Statement of Interest” form is received on time.
- DO NOT submit any unrequested additional documents (e.g., CV, certificates, etc.) until asked to do so.
- You are welcome to contact the corresponding project supervisor(s) if you have specific scientific questions on a research project. However, DO NOT send any application material directly to the project supervisors.
If you have questions on the recruitment procedure, please refer to the FAQ first. If your questions persist, please contact apply-jsmc(at)uni-jena.de.
