We are looking for a motivated PhD candidate in the field of biomolecular solid-state NMR combined with Dynamic Nuclear Polarization (DNP), for a start in Fall 2023 (or earlier).
The PhD student will be involved in a highly interdisciplinary research project at the frontiers of Chemistry, Biology and Physics. The aim is to continue the development of selective hyperpolarization NMR approaches and combine them with site-specific isotopic labeling for the investigation of active sites in large biomolecular assemblies.
PhD context and objective: Dynamic Nuclear Polarization (DNP) has emerged as a promising hyperpolarization technique for solid-state NMR. Nevertheless, for biomolecules, the spectral resolution is often strongly impacted by the use of cryogenic temperature. The DNP-NMR team at CEA Grenoble recently introduced a new methodology, called Selective DNP (SelDNP), which allows recovering high-resolution DNP spectra for specific parts of the protein . This targeted DNP-NMR approach  combines paramagnetic tagging (radical-functionalized ligand, spin label, paramagnetic metal ion, etc.) and differential spectroscopy. It was demonstrated to reveal the carbohydrate-binding site of the protein LecA (12 kDa). Thanks to the expertise of NMR-Bio, a translational contract research organization (http://www.nmr-bio.com), in advanced specific isotopic spin labeling , we propose to extend this emerging and promising SelDNP methodology to large biomolecules. As a proof of concept, we will first focus on a chondroitin sulfate 4-endosulfatase (ENDO-4sulfatase, 58 kDa) expressed by Prevotella oris, a bacteria of the human gut microbiota. Sulfatases are important and yet poorly understood enzymes, which play a key role in regulating the sulfation states of many important substrates, including complex cell-surface polysaccharides. Ultimately, the development of the SelDNP methodology should provide new solutions for investigating protein/glycan interactions and glycoenzymes.
 I. Marin-Montesinos, D. Goyard, E. Gillon, O. Renaudet, A. Imberty, S. Hediger and G. De Paëpe, Chem. Sci., 2019, 10, 3366.
 D. Gauto, O. Dakhlaoui, I. Marin-Montesinos, S. Hediger and G.De Paëpe, Chem. Sci., 2021,12, 6223.
 R. Kerfah, MJ. PLevin, R. Sounier, P. Gans and J. Boisbouvier, Current Opinion in structural Biology, 2015, 32:113-122.
Required background: Background in biochemistry and biophysics is required, with a strong interest in structural biology and physical chemistry (including NMR spectroscopy). Practical knowledge in protein production and overexpression is recommended. Basic knowledge in (solid-state) NMR spectroscopy would be an asset.
Application: Interested and motivated candidates can apply by email to email@example.com and firstname.lastname@example.org. Please provide:
- your CV
- a motivation letter
- M1 and M2 marks and ranking
More information about the position can be found here and about our group at https://nmr-dnp-grenoble.net.
Grenoble is one of the major cities in Europe for research with a large international scientific community. In addition, Grenoble has a large international student population, is a very pleasant city to live in, and is known as the “Capital of the Alps” with easy access to great skiing and hiking. It’s also only 2 hours’ drive to the Mediterranean Sea, Italy, or Switzerland. Grenoble, Lyon, and Geneva airports are nearby and permit straightforward international travel.