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Reference : UMR5075-JERGAU-013
Workplace : GRENOBLE
Date of publication : Wednesday, September 8, 2021
Scientific Responsible name : Darren HART
Type of Contract : PhD Student contract / Thesis offer
Contract Period : 36 months
Start date of the thesis : 1 January 2022
Proportion of work : Full time
Remuneration : 2 135,00 € gross monthly
Description of the thesis topic
The thesis project aims to develop new peptide-based inhibitors of influenza virus through a combination of structural biology, protein engineering, cell biology and peptide chemistry. There is an important need for new antivirals as a complement to vaccination due to issues of viral resistance. Phage display directed evolution (see Nobel Prize in Chemistry 2018) will be used to generate high affinity peptide inhibitors of viral and host protein complexes that are essential for influenza virus replication. Hits will be characterised using biophysical methods and X-ray crystallography at the facilities of the EPN Campus in Grenoble, followed by cellular assays of virus replication in collaboration with the Institut Pasteur, Paris. Working with our peptide chemistry partner at the University of Grenoble Alpes (UGA), peptides will be improved by chemical modification to improve their properties of cellular import, target-binding and stability. Initial results have been obtained in our lab, indicating the feasibility and exciting potential of this approach.
The PhD student will work in the Virus Replication Machines (VRM) group of the Institut de Biologie Structurale (IBS) in Grenoble, supervised by Darren Hart. The IBS (www.ibs.fr) is afilliated with the CNRS, the CEA and the UGA, and is located on the EPN Campus. This site is recognised globally for its research in structural biology with large instruments, notably the European Synchrotron Radiation Facility (ESRF), and a dozen smaller platforms providing all necessary tools for structural biology research e.g. biophysics, electron microscopy, NMR, mass spectrometry, protein crystallisation, etc. (www.isbg.fr). The project is funded for 3.5 years by the French National Research Agency (ANR) and involves consortium partners at the Institut Pasteur and the UGA with whom the student will interact. The student will participate and present project results at local and national events organised by local and national communities including the IBS, the Partnership for Structural Biology (PSB; www.psb-grenoble.eu), the UGA Chemistry & Life Sciences Doctoral School (EDCSV) and the RESAFLU network.
The candidate must have a Masters in biology or biochemistry. The post requires sound knowledge of molecular biology and interests in areas such as virology, drug discovery, protein engineering and/or structural biology, plus a basic knowledge of bioinformatics. A high level of communication skills in English, both oral and written, is required to be able to present at conferences and write articles in scientific publications.
Applications must include a detailed CV; at least two references (people who may be contacted); a cover letter of one page; a short summary of the dissertation for the Masters degree (or equivalent); grades for the Masters 1 and 2 or diploma.
Constraints and risks
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