Institut de Chimie Moléculaire et des Matériaux d'Orsay


Synthèse de Molécules et de Macromolécules

pour le Vivant et l’Environnement

Chemical tools for the study of epigenetic modifications

Epigenetics defines the changes in gene expression that are not coded by the DNA sequence and are inheritable. The main epigenetic factors are chemical modification of histones (methylation and acetylation) and DNA methylation, but new modifications have recently expanded the epigenetic landscape. Considering the potential of “druggability” of proteins involved in epigenetics, the precise characterization of their activity might offer new opportunity for therapeutic intervention. In recent years, the study of chromatin biology has greatly benefited from chemical biology tools to address fundamental structure/function problems in epigenetics. We recently developed both chemical tools and proteomic approaches based on photolabeling or bioorthogonal labeling coupled to mass spectrometry to study several epigenetic modifications.

Trehalose and mycolic acid-based probes for the study of mycomembrane biogenesis

Recently, chemical-biology-based strategies have emerged for the study of bacterial pathogens, giving biologists the opportunity to have powerful new tools for probing bacteria. Actually, probes for the study of mycobacterial envelope remains challenging since Mycobacteria and Corynebacteria have an atypical organization being composed of complex glycolipids (mycolic acids esterified to α,α-D-trehalose). They form a very impermeable and rigid barrier that might contribute to the exceptional resistance of mycobacteria towards chemotherapeutic molecules. The biosynthesis of these cell wall mycolate esters has been studied during the last decade but the mechanisms of their assembly in the bacterial envelope is largely unknown.

In this context, we study the specificity and the interplay between several enzymes named mycoloytransferases in the biogenesis of the envelope of these mycobacteria, using our expertise in trehalose chemistry including the synthesis of complex fatty acids and selective modifications of trehalose. We work in this project in close collaboration with Prof. Nicolas Bayan (Institut de Biologie Intégrative de la Cellule, Université Paris Sud), Dr. Boris Vauzeilles (Chemical Biology Department, Institut de Chimie des Substances Naturelles) and with Prof. Federica Migliardo (University of Messina).