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Genetics and Chemogenomics team (Gen&Chem)

Published on 21 August 2020



Leader

Marie-Odile Fauvarque

Laboratoire Biologie à Grande Échelle
CEA-Grenoble
17 avenue des Martyrs
38 054 Grenoble cedex 09

Composition of the team

Laurence Aubry, PhD
Caroline Barette, PhD, Automated screening of compounds libraries
Julie Bourget, administrative
Alexandre Bouron, PhD
Gilles Courtois, PhD
Marjorie Comte, Research assistant
Marie-Odile Fauvarque, PhD
Agnès Journet, PhD
Magda Mortier, Research assistant
Catherine Pillet, Research assistant
Emmanuelle Soleilhac, PhD, Cell profiling using automated microscopy
Emmanuel Taillebourg, PhD
Waltrich Augusto Thierry, PhD student


Presentation

The team develops genetics and chemogenomics approaches for the identification and study of proteins and small chemicals functions in cell signalling. The team pursues both a research project which aims in the characterization of novel mechanisms of regulation of innate immune and inflammatory signals, and facilities and R&D activities at the Center for the screening for BioActive Molecules (CMBA).

The research activity of the team aims to provide fundamental insights into the role of the ubiquitin system in signal transduction and endocytosis of plasma membrane receptors that provide appropriate cellular responses to cell growth or differentiation signals. Special attention is given to deubiquitinating enzymes (DUBs) of the ubiquitin-specific protease subfamily that regulate inflammation or cell growth. These DUBs are known therapeutic targets in several pathologies, including chronic inflammation, cancer or rare diseases (Cushing’s disease) but their substrates and mechanisms of action are still poorly known. The team is also studying, in collaboration with European groups, the developmental function of a ubiquitin binding protein (NEMO, NF-kB Essential MOdulator) that plays a major role in inflammation and whose mutations cause the rare disease Incontinentia pigmenti. Finally, the team collaborates with Prof. Ramesh Pillai (Geneva Univ.) To understand some epigenetic mechanisms of development related to the biology of the RNAs. The research of the team is based on the implementation of molecular genetics, transgenesis, mutagenesis and cell biology strategies on mouse, murine or Drosophila fly models.

The CMBA center, (“Criblage pour des Molécules BioActives”, CMBA) is an open platform which is dedicated to the screening and discovery of bioactive molecules.

The platform ensures:
• Facilities and collaborative activities for the High Throughput Screening (HTS) of chemicals libraries on cellular or biochemical assays, including statistical analysis of the results,
• A Research & Development activity for improving the analysis of cell phenotypes by High Content Screening imaging (HCS), including statistical analysis of results,
• A training activity on HTS and HCS.

In addition to their therapeutic potential, small molecules present many advantages for research purposes. They are irreplaceable tools for probing dynamic phenomena and inducing reversible effects in some cases.

The CMBA platform works in close collaboration with the DPM-Expert platform of the Department of Molecular Pharmacology (DPM) at Grenoble Alpes University, headed by Professor Ahcène Boumendjel. The DPM-Expert platform provides expertise in medicinal chemistry and collections of original chemicals, including extracts from alpine flora. Together, the two platforms constitute the Grenoble Alpes Drug Discovery (GAP2D) consortium, labeled by GIS-IBiSA pledge of open access and reliability for the acquisition, analysis and storage of data.


The CMBA is a member of the CHEMBIOFRANCE national infrastructure
The Center for the screening for BioActive Molecules (CMBA) of the BGE laboratory participates to the national infrastructure ChemBioFrance. This infrastructure was designed to encourage and stimulate exchanges and services at the interfaces between the chemistry of biology and chemoinformatics in order to select bioactive molecules that can be used for basic or therapeutic research purposes. ChemBioFrance is a distributed infrastructure that interconnects the French national chemical library, the platforms for the screening and the pharmacokinetic studies (ADME), and molecular modeling laboratories (chemoinformatics). It is open to researchers from academic and private laboratories.
Contact: Marie-Odile Fauvarque
More information.


Key words

- Cell signaling; Intracellular trafficking; Endocytosis; Inflammation; NF-kappaB; Ubiquitin; Ubiquitin-specific proteases; USP2; USP8; USP36
- Cancer; Oncogenesis; Rare diseases; Incontinentia pigmenti; Cushing's disease
- Automated molecular screening; Drug Discovery; Therapeutic targets