DUFOURC Erick

Membrane dynamics

Solid state NMR is one of the best techniques to decipher membrane dynamics on time scales ranging from picoseconds to seconds (insert). We currently use two NMR observables: motion averaged spectra and relaxation times. Nuclei of interest are 1H, 2H, 31P, 13C, 15N. They provide information on order parameters, phase transitions, correlation times, activation energies and membrane elasticity. These physical parameters provide us with tools to understand the biological mechanisms (fusion, leakage, adsoption, permeability, etc.) that occur at the cell membrane.

We are also interested in membrane sterols which are very important molecules in life and play a crucial role in membrane dynamics. They modulate membrane phases, order parameters, correlation times and membrane elasticity. In general, sterols tend to reduce the impact of environmental changes on the order and dynamics of molecules. They can be described as “regulators of membrane dynamics” by keeping them in a state of dynamics that changes very little when the temperature or other factors change. The mechanism of action of amphipathic peptides on membranes can also be discovered using solid-state NMR. Peptide-lipid complexes exhibit a wide range of structures and dynamics: carpet-like, barrel stave, toroidal and disordered pore, electrostatic wedge and molecular electroporation assemblies are commonly observed.

More reading: Morvan et al., BBA, 2022; Anal. Chem., 2023; Dufourc, J. Chem. Biol., 2008; Dufourc et al. Curr. Protein Pept. Sci., 2012.

Myelin dynamics (ANR ULTIMO)

Myelin is a lipid and protein lamellar membrane structure that tightly envelops the axon in a concentric fashion (see insert). It serves as an electrical insulator to transport electricity (nerve impulses) along the axon in nervous systems. In many neurodegenerative diseases, myelin loses its tight cochlear structure, which is primarily held together by two proteins, myelin basic protein (MBP) and proteolipid protein (PLP), resulting in a detachment mechanism that releases the axon membranes. Although great progress has been made in brain imaging, it is still very difficult to specifically probe myelin membranes and their changing dynamics.Our project, shared with colleagues from Marseille, aims at better understanding these phenomena, both from the point of view of magnetic resonance imaging (MRI) and solid state nuclear magnetic resonance (ssRMN). Special techniques will be developed to try to image myelin in the brain (inhomogeneous magnetization transfer ihMT-MRI) and to determine which membrane motions are responsible for the image contrast and the detection of myelin dysfunction at the molecular level (Jeener-Broekaert dipolar echoes and Dipolar spin-lattice relaxation).

Erick Dufourc graduated in physical chemistry from the University of Bordeaux, France, in 1980, and obtained a PhD in biophysics from the University of Ottawa/National Research Council, Canada, in 1983. He joined the CNRS (Centre National de la Recherche Scientifique, France) in 1983 and obtained a state doctorate (DSc) in Physical Sciences from the University of Bordeaux, France, in 1986, working on solid-state NMR of lipids and peptides. After a sabbatical in Stuttgart (Humbolt Foundation laureate), Germany, where he worked on the theory of membrane dynamics, he returned to Bordeaux and obtained a position as director of research at CNRS and a chair at the University of Bordeaux, to develop NMR of soft matter. In 1998, he was one of the founders of the European Institute of Chemistry and Biology (IECB) where he led the "Biophysics of Membrane Assemblies" group and developed a unique platform of NMR spectrometers to work on the structural biology of membranes. In 2006, he created and directed for 11 years the Institute of Chemistry and Biology of Membranes and Nanoobjects (CBMN), an interdisciplinary institute gathering 200 chemists, physicists and biologists in Bordeaux. At the same time, he has also developed with other French scientists the TGIR RMN THC (France Large scale infrastructure of high field NMR spectrometers). The Bordeaux site is dedicated to NMR for "membrane and colloid sciences". He has been president of several scientific societies (EBSA, GERM, GEM, SFC Aquitaine, etc.) and served for 8 years in the Ministry of Foreign Affairs in the framework of bilateral scientific relations between France and India and France and Pakistan. In 2017, he was appointed Deputy Scientific Director of the Institute of Chemistry at the CNRS headquarters in Paris, in charge of chemical biology and molecular and supramolecular chemistry in France.
He became Emeritus Research Director of the CNRS in 2021 and continues his activity at CBMN/IECB in Bordeaux.
He is currently developing three lines of research in structural biophysics: i) membrane dynamics: lipids, sterols, peptides and proteins, ii) role of aluminum-based adjuvants in vaccines and iii) structure and dynamics of myelin in healthy and diseased brains.
He wrote more than 200 papers and book chapters and gave more that 150 conferences.
ORCID: 0000-0002-8221-9326