Integrative Biological NMR

Our research focuses on the development of NMR methods and their applications, together with other biophysical techniques, in structural biology and to the biophysics of membranes, to characterize virulence factors or therapeutic targets associated with cancers or pathogen-host relationships, with a particular focus on mycobacterial infection.

An interdisciplinary research group elucidating molecular structure, dynamics, and interactions of biological processes using NMR, biophysical methods, and MD simulations.

The Integrative Biological NMR group applies its expertise and state-of-the-art equipment to pursue ambitious projects in structural biology with important implications in pharmacology. The study of structure, dynamics, and interactions of biomolecules are key to elucidating biochemical processes at atomic resolution. We continuously explore new avenues, such as the structure and function of complex membrane assemblies, and the influence of macromolecular dynamics on interactions, in the context of bacterial infection and cancer.

The relationship between host and pathogen is mediated by numerous biological processes. The molecular mechanisms by which the host detects and responds to infection by pathogens and by which pathogens circumvent host defences are of primary relevance to the development of novel therapeutic approaches.

– We are seeking to understand the defence mechanism of Mycobacterium tuberculosis against metal intoxication in human phagocytes, and to decipher the host’s response to pathogens mediated at a molecular level by a family of cell surface receptors. Upon infection by Mtb, macrophages attempt intoxication of the bacterium via an increase in the concentration of metals such as copper and zinc. In this context, the group of Dr. Olivier Neyrolles (IPBS) has identified three P1-type ATPases of Mtb (CtpC, CtpG and CtpV), each co-expressed with a small membrane-associated protein, PacL1, PacL2 and PacL3, respectively. While CtpC is required for optimal intracellular survival of Mtb at high zinc concentrations, PacL1 is required for zinc resistance in Mtb, it colocalises in foci with CtpC, and it stabilises CtpC efflux platforms at the plasma membrane. PacL1 therefore represents a novel type of metallochaperone in the sense that it binds zinc and stabilises CtpC. We are studying the selectivity of these metallochaperones towards metals and the mechanism of metal transfer towards the associated transporter.

– C-type lectin receptors (CLRs) are host proteins that play key roles in the innate immune system. CLRs allow cells to recognise characteristic molecules of pathogens or damaged cells and to trigger signalling pathways that culminate in protective effects. A better understanding of CLR signalling at the molecular level may facilitate the development of therapeutic agents targeting these receptors. Limited structural data is available, however, shedding only some light on ligand recognition. We focus specifically on a set of transmembrane CLRs (Mincle, Dectin-1, Dectin-2 and DCIR) that play key roles in pathologies such as infection, by Mtb and other bacteria, cancers, and autoimmune diseases. These CLRs are representatives of diverse signalling mechanisms. We aim to provide a detailed explanation of the allosteric coupling between extracellular ligand binding and intracellular partner protein recruitment that results in immune cell response.

Team members

Research Scientists

Andrew Atkinson (CNRS)
Georges Czaplicki (University)
Pascal Demange (CNRS)
Guillaume Ferré (University)
Evert Haanappel (CNRS)
Alain Milon (University)
Isabelle Muller (University)
Valérie Réat (CNRS)
Olivier Saurel (CNRS)

Research Engineers

Dunkan Bégué
Nathalie Doncescu (CNRS)
Yasmina Grimoire
Pascal Ramos (University)

PhD Students

Floriane Audebert
Louis Benastre
Maxime Noriega

Our research projects

Deciphering the architecture and function of bacterial membrane efflux platforms

Understanding immune cell signalling through C-type lectin receptors

Further collaborations

Ferré et al. (2023) Sodium is a negative allosteric regulator of the ghrelin receptor. Cell Rep

Schahl et al. (2022) Evidence for amylose inclusion complexes with multiple acyl chain lipids using solid-state NMR and theoretical approaches. Carbohydr Polym

Ferré et al. (2019) Structure and dynamics of G protein-coupled receptor-bound ghrelin reveal the critical role of the octanoyl chain. Proc Natl Acad Sci USA

Augenstreich et al. (2019) The conical shape of DIM lipids promotes Mycobacterium tuberculosis infection of macrophages. Proc Natl Acad Sci USA

Saurel et al. (2017) Local and global dynamics in Klebsiella pneumoniae outer membrane protein a in lipid bilayers probed at atomic resolution. J Am Chem Soc

Carel et al. (2017) Identification of specific posttranslational O-mycoloylations mediating protein targeting to the mycomembrane. Proc Natl Acad Sci USA

Macromolecular interactions by NMR: Solution structure of the THAP zinc finger of THAP1 in complex with its DNA target (PDB entry 2KO0). © Olivier Saurel