Integrated structural biology of nucleoprotein complexes

Our team http://www.igbmc.fr/Klaholz uses an integrated structural biology approach to study the structure and function of various macromolecular complexes involved in transcription, translation and other molecular mechanisms involved in diseases, in particular cancer. The aim of the postdoctoral project would be to investigate the structure of full nuclear receptors or other nucleoprotein complexes such as ribosomes or viruses using any of the methods used in the team (see keywords below) and/or participate in the developments of new tools where needed. Nuclear receptors in particular are DNA-binding proteins that can be activated by binding hormones or other endocrine ligands. The structure of ligand-binding and DNA-binding domains is known in some cases, but only few high-resolution structures exist for the full-length assemblies bound to the DNA (comprising direct or inverted DNA repeats); hence, understanding the overall architecture and the detailed molecular interactions in such complexes is a key question to address. Cryo-EM and new image processing methods are currently making major advances such that relatively small complexes (DNA-bound NRs are in the 100 kDa range) can be analysed. Other possible projects comprise pushing resolution of ribosome complexes to below 2Å to resolve RNA chemical modifications and drug substituents, study translation initiation complexes or virus/phage complexes, or study any of these complexes in their cellular context using FIB & cryo electron tomography. Background can by from biology, biochemitry, cell biology, structural biology, medicine, pharmacy, chemistry, physics, mathematics or informatics as the approaches used in the team are highly interdisciplinary and often involve new developments to enable structure-function analysis of the macromolecular complexes of interest. Latest-generation instrumentation (FIB, two Titan Krios cryo electron microscopes etc.) is available onsite at the CBI/IGBMC at part of the national and European FRISBI & Instruct-ERIC infrastructures http://www.igbmc.fr/grandesstructures/cbi.

https://euraxess.ec.europa.eu/jobs/hosting/integrated-structural-biology-nuclear-receptor-and-nucleoprotein-complexes