PhD position in Paris, France - Hyperpolarised method developments to study the metabolism of glutamine #DNPNMR

Published: Thursday, 20 April 2023 - 10:00 -0400

Author: Thorsten Maly

Dear colleagues,

We are hiring a motivated and hard-working candidate for a PhD position at Université Paris Cité in the frame of an ANR-granted project, to study the use of glutamine as a hyperpolarised biomolecular tracker using dissolution dynamic nuclear polarisation.

Glutamine is a key-player in cellular energetic supplies. The deregulation of its metabolism has been shown to play a role in some pathologies such as cancer or cardiovascular dysfunctions. Using NMR, we will study its metabolism in cellular models in real-time as well as the effect of potential drugs. While NMR is a powerful tool and enables to monitor dynamic processes such as chemical reactions, it suffers from an intrinsic weak sensitivity which can lead to long signal acquisition times and reduce its temporal resolution. Among the techniques used to enhance NMR sensitivity, dissolution dynamic nuclear polarisation (D-DNP) is the most versatile and enables to reach signal enhancements up to four orders of magnitudes over several tens of seconds by using a dedicated piece of hardware, the polariser, coupled to a classic NMR spectrometer or MRI scanner. [1-2]

This PhD project will be supervised by Mathieu Baudin (Université Paris Cité and École Normale Supérieure) and Nicolas Giraud (Université Paris Cité). We combine areas of expertise ranging from inorganic chemistry to supramolecular chemistry and analytical chemistry involving Nuclear Magnetic Resonance (NMR) as well as hyperpolarisation hardware. This present offer focuses on hyperpolarisation and cellular metabolism, to develop hardware and methods dedicated to sensitivity enhancements for the study of biological samples.

In this project, we will develop methods in NMR enhanced via D-DNP to study the cellular metabolism of glutamine through in vitro enzymatic reactions, as well as experiments on cell extracts and live cells. The aims will be to develop hyperpolarisation hardware, specific DNP samples, and innovative detection NMR sequences dedicated to hyperpolarised NMR in order to study the metabolic reactions in real time, detect and identify metabolites at low concentrations and test the effect of anti-metabolic drugs [3].

We seek a motivated candidate to join our team. They will be in charge of preparing, optimising and handling NMR samples dedicated to hyperpolarization by DNP, implementing and optimizing NMR experiments regarding detection schemes and biological applications, and analysing and modelling the resulting NMR data. They will be located in a dynamic and international research team at LCBPT at Université de Paris (CNRS UMR 8601), a biomedical research centre of excellence located downtown Paris, France. In addition, a significant part of the experiments foreseen in this project will be performed at École Normale Supérieure at the Laboratory of Biomolecules (CNRS UMR 7203) as the two groups collaborate tightly and share a hardware platform for D-DNP.

Applicants should have a degree in chemistry, or an engineering degree with strong background in chemistry. Experience with NMR spectroscopy and data analysis would be appreciated. We are looking for a hard-working and highly motivated candidate. The eligible candidate will be funded for three years by a grant from the French Research Ministry (ANR grant ANR-22-CE29-0003-01 PolarGlu).

Références:

[1] J. H. Ardenkjaer-Larsen, J. Magn. Reson., 2016, vol. 264, pp. 3–12, https://doi.org/10.1016/j.jmr.2016.01.015
[2] M. Baudin et al., J. Magn. Reson., 2018, vol. 294, pp. 115–121, https://doi.org/10.1016/j.jmr.2018.07.001
[3] K. Dos Santos et al., ChemPhysChem, 2023, e202300151, https://doi.org/10.1002/cphc.202300151

Contact:
If you are wishing to apply, please send CV, cover letter and contact information for two/three references to: mathieu.baudin@u-paris.fr • CNRS, Université Paris Cité, École Normale Supérieure

Websites: https://lcbpt.biomedicale.parisdescartes.fr/nmr / https://www.chimie.ens.fr/recherche/laboratoire-lbm/structure-and-dynamics-of-biomolecules/

Best regards,
Mathieu Baudin


Mathieu Baudin
CNRS research Engineer, PhD

UMR 8601
Laboratoire de Chimie et Biochimie Pharmacologiques Toxicologiques
Université Paris Cité - Campus Saint Germain des Prés
45 rue des Saints Pères 75006 Paris
+33 1 76 53 42 02

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