[PhD defence] 03/07/2024 - Marine Soulié: "Design, synthesis and characterisation of chemical tools for the study of membrane proteins" (UPRI - Synthesis and Bio-organic Colloidal Systems Laboratory (S2CB))

Date and place

Oral defense scheduled on wednesday 03 july 2024 at 10.00 am
Venue: Avignon University Institut Agrosciences, Environnement et Santé - Bâtiment A Campus Jean-Henri Fabre 301 rue Baruch de Spinoza BP 21239 84916 AVIGNON cedex 9
Room: Amphithéatre Agrosciences

Discipline

Chemistry

Laboratory

UPRI - Synthesis and Bio-organic Colloidal Systems Laboratory (S2CB)

Management

MR GREGORY DURAND

Avignon University - UPRI - Synthesis and Bio-organic Colloidal Systems Laboratory (S2CB)

Composition of the jury

MR GREGORY DURAND	Avignon University - UPRI - Synthesis and Bio-organic Colloidal Systems Laboratory (S2CB)	Thesis supervisor
Thierry DURAND	Institut des Biomolécules Max Mousseron (IBMM) UMR 5247 - CNRS - UM - ENSCM Pôle Chimie Balard Recherche	Rapporteur
Ms Christine GERARDIN	University of Lorraine - Wood Materials Research Laboratory	Rapporteur
Ms Manuela ZOONENS	Université Paris Cité - Physical and Chemical Biology of Membrane Proteins Laboratory - UMR 7099	Examiner
Ms Catherine DUPORT	Avignon University - Safety and Quality of Plant Products Laboratory - UMR 408	Examiner
Ms Kerstin KANONENBERG	Company Eurofins Calixar	Guest

Summary

This thesis focuses on the design, synthesis and characterisation of chemical tools for the extraction and stabilisation of membrane proteins. It is part of the process of obtaining a doctorate through validation of prior learning (VAE), which highlights the most significant results obtained over the last ten years of my professional career, as presented in Chapter 1.

Membrane proteins are major therapeutic targets, and their study is essential for the development of new clinical solutions. These proteins are amphiphilic and fragile outside their native environment. Chemical tools are needed to extract them from the lipid bilayer in which they reside and keep them soluble and functional so that they can be characterised. A presentation of existing chemical tools for manipulating membrane proteins is given in Chapter 2.

The rationales that guide the development of new generations of tools and the resulting optimisation of structures are also presented. Particular emphasis is placed on detergents and polymers. These are two families widely used by biochemists to extract, stabilise and purify membrane proteins prior to structural and functional studies.

Chapter 3 summarises my work in synthetic chemistry and colloidal physico-chemical characterisation, as well as the results obtained on the modulation of the solubilising and stabilising properties of new tools. The introduction of a fluorinated hydrophobic unit has, for example, enabled the development of zwitterionic detergents with a polar sulphobetaine or amine-oxide head, and perfluorinated cyclic detergents with a maltose head, whose 'extractant/stabilising' behaviour can be finely adjusted. The design of non-ionic additives, aimed at improving protein stabilisation, is also illustrated by their synthesis from a calixarene platform and, more recently, on the basis of a cholesterol unit, which is particularly well suited to the class of receptors coupled to G proteins. Finally, the work carried out on approaches using non-ionic polymers of the NAPol type is presented as an alternative to the use of 'conventional' detergents for stabilising protein targets.

Key words :

Detergents, Amphiphiles, Polymers, Membrane proteins, Organic synthesis, Colloids