PHD STUDENTSHIP IN BIOPHYSICS
Joint project between the High Field NMR Center (CRMN) of the ENS Lyon, the Laboratory of Bioimaging and Pathologies (LBP) at the University of Strasbourg and SANOFI Pasteur
From September 2022
CNRS 80 Prime scholarship for cutting-edge interdisciplinary research
TITLE OF THE PROJECT
Understanding supramolecular architectures of mRNA-loaded lipid nanoparticles
We are looking for a highly motivated candidate with background in structural and molecular biology, biochemistry, physical chemistry or biophysics, and a strong interest in spectroscopic techniques and in their applications to biomolecules and pharmaceutical research.
Nucleic acid therapies are expected to revolutionize the treatments of a large number of diseases. The potential of RNA- and especially messenger-RNA-based medicines has been remarkably illustrated by the recent development of vaccines against SARS-Cov-2. To deliver mRNA in cells, lipid nanoparticles (LNPs) are the most advanced platforms, protecting mRNAs from nucleases, allowing their efficient uptake by the cells and their escape from endosomes into the cytosol, where they are translated into the antigenic protein. The architecture of mRNA-LNPs plays a key role in the stability of mRNA and its expression in cells, but remains still largely unknown.
The aim of this multidisciplinary project is to characterize the architecture of LNPs, including their topology, the location of the mRNA, its hydration and specific interactions with lipids, by two complementary approaches using innovative NMR and fluorescence techniques, as well as state-of-the art instrumentation developed in the two labs. The project will be carried out jointly between two prestigious laboratories, the CRMN (Lyon) and the LBP (Strasbourg), in partnership with Sanofi Pasteur. At the CRMN, the candidate will notably develop high-sensitivity solid-state NMR approaches with fast Magic Angle Spinning (MAS) and/or Dynamic Nuclear Polarization (DNP) to probe the nm-scale architecture of LNPs. At the LBP, the candidate will implement state-of-the art steady-state and time-resolved fluorescence spectroscopy using tailor designed sensitive molecular probes located either on the lipids or on the RNA. Model as well as pharmaceutically relevant assemblies will be investigated.
The PhD candidate will work in both labs, with a balanced time sharing, with severalmonth / one-year periods in Lyon and in Strasbourg. The CRMN is a first-class laboratory hosting a unique ensemble of NMR spectrometers fully equipped for the analysis of a large variety of samples in solution and in the solid-state, and operated by young, dynamic and internationally recognised scientists. The LBP is equipped with advanced fluorescence spectroscopy and QUEST microscopy platforms, and is a leading laboratory in the investigation of molecular and cellular mechanisms involved in many diseases and in the development of new therapeutic clues.