Structural studies of simplified RNA polymerases for engineering and drug design

The Institut Pasteur is a large scientific organisation located in central Paris with a worldwide reputation in Biology and Microbiology.
It is well connected to public transportation, including Metro lines and trains to south and south-west suburbs.
It is made of 12 Departments and 4 technological or translational Centers that include key technological platforms.
The Department of Structural Biology and Chemistry includes about 150 people: researchers, post-docs, engineers, technicians and students, with strong interactions and shared interests.

A post-doctoral fellowship for 2 years in structural studies of highly simplified versions of RNA polymerases from phages or parasites is available in the lab of Architecture and Dynamics of Biological Macromolecules at Institut Pasteur, Paris (http://dynstr.pasteur.fr, Head Marc Delarue).

The core expertise of the lab is in the field of structural biology, especially of DNA and RNA polymerases, giving crucial information that is used as input for protein engineering and design. Another aspect is the design of drugs against viruses or parasites.

Some phage RNA polymerases that are simpler than their eukaryotic or bacterial ones could be used as workable templates for directed evolution and enzyme engineering techniques, which we have implemented in the past 3 years in the lab on DNA polymerases. Detailed structural information on these enzymes is needed to proceed.

On another aspect, some RNA polymerases from parasites are sufficiently different from their hosts to make them druggable targets.

Access to excellent specialized platforms and facilities is granted in electron microscopy (1 Titan and 2 Glacios), protein expression and purification, NMR and mass spectrometry, as well as biophysics.

Potential applications concern finding working drugs against RNA polymerases of parasites as well as the design of RNA polymerases with the ability to incorporate modified nucleotides, or even to amplify RNA in PCR-like cycles.

We seek a post-doctoral fellow with a high profile to re-enforce these axis.

Institut Pasteur is a leading institution in fundamental molecular biology and applied microbiology in Europe. It is an equal opportunity employer that allows many cross-disciplinary collaborations within the campus in a dynamic and enriching environment, in the center of Paris.

Candidates should have a proven expertise in protein expression, purification and cryo-EM single-particle analysis.

We are looking for a structural molecular biologist or biochemist with experience in solving structures of biological macromolecules by cryo-EM techniques, all with a PhD degree in one of the aforementioned fields.
 

This CDD is for two years, but an extension by 1 year is possible.