Université de Strasbourg

Nicolas Matt

Biography

Laboratory for Innate Immune Response in Insect Models (M3I), Institute for Molecular and Cellular Biology (IBMC), University of Strasbourg and CNRS

Nicolas Matt , USIAS Fellow 2018

Dr. Nicolas Matt carried out his thesis at the Institute of Genetics and Molecular and Cell Biology (IGBMC) in the team of Professor Manuel Mark and Dr. Norbert Ghyselinck, where he worked on the transcriptional regulation of nuclear receptor target genes by retinoic acid. In 2004, he obtained a PhD in Biology and Molecular Genetics from the Louis Pasteur University in Strasbourg (France), and subsequently completed a postdoctoral fellowship at the University of Basel (Switzerland).

In 2006, he was appointed lecturer at the University of Strasbourg and joined the French National Centre for Scientific Research (CNRS) research unit for Immune Response and Development in Insects (RIDI) at the Institute for Molecular and Cellular Biology (IBMC). He was awarded the 2015 prize “Les espoirs de l’Université de Strasbourg” awarded by the university to promising young researchers, and obtained the habilitation to direct research in 2016 and has since led his own team within RIDI, recently renamed as the laboratory for Innate Immune Response in Insect Models (M3I). His research focuses on deciphering the molecular mechanisms that regulate and orchestrate the transcription of NF-kB factor target genes during the innate immune response. His team is part of the Labex NetRNA: Networks of Regulatory RNAs across kingdoms and dynamical responses to biotic and abiotic stresses.

Nicolas Matt furthermore manages, with Dr. Bertrand Séraphin (Director of IGBMC), the Graduate School project “Integrative Molecular and Cellular Biology” (EUR-IMCBio).

Project - Exploration of the chromatin inflammatory code in Drosophila and in mammals

October 2018 – June 2021

NF-kB transcription factors are key players in the transcriptional cascade leading to inflammation, where they activate genes with pro- or anti-inflammatory activities. Tremendous efforts have been made to develop drugs that can interfere with NF-kB signaling in inflammatory diseases. However, complete shutdown of the NF-kB pathway can lead to many adverse effects. In this context, our laboratory made the discovery of akirine, a conserved protein of the NF-kB pathway that is necessary for the transcription of pro-inflammatory genes, but not for NF-kB-dependent genes that contribute to the down-regulation of inflammation. This discovery points to a dichotomy in NF-kB target genes between the activation of akirine-dependent and -independent genes, which allows - for the first time – the dissociation of the activation and resolution mechanisms of inflammation. We have been able to show that the SWI/SNF (SWItch/Sucrose Non-Fermentable) chromatin remodeling complex, combined with an epigenetic modification of histones, are specific factors of this dichotomy. A more recent study has revealed that epigenetic marks are determinant for the selective recruitment of chromatin remodeling complex which are essential for the good expression of genes. Collectively this suggests the existence of a distinctive epigenetic code that is triggered as part of the process of inflammatory response in order to activate akirine-dependent genes during inflammation.

Our main aim will be to decipher this code. To this end, we intend to combine genetic approaches used in Drosophila and murine cell lines with whole genome-wide exploration methods in order to explore the epigenetic change and chromatin remodeling that accompany immune stimulation. This project will provide a full overview of the inflammatory process at a molecular level and deliver new insights into the mechanisms that govern the transcriptional selectivity of NF-kB factors.

Post doc biography - Alexandre Cammarata-Mouchtouris

Laboratory for Innate Immune Response in Insect Models (M3I), Institute for Molecular and Cellular Biology (IBMC), University of Strasbourg and CNRS

Alexandre Cammarata-Mouchtouris

Dr. Alexandre Cammarata-Mouchtouris has an academic background in physiopathology and immunology (University of Strasbourg). In 2018, he obtained his PhD degree in Strasbourg under the supervision of Dr. Nicolas Matt and Professor Jean-Marc Reichhart. His thesis focused on the study of the innate immune system regulation in Drosophila melanogaster. After immune stimulation, stopping the molecular pathways of immunity, such as the NF-κB pathway, is necessary to prevent the development of autoimmune diseases or cancer. The similarity of those pathways in insects and mammals makes Drosophila an excellent model for exploring the immune response. Dr. Cammarata-Mouchtouris worked on understanding a time-dependent mode of regulation and the involvement of chromatin remodeling machinery in controlling the expression of Drosophila NF-κB pathways.

Within the USIAS project, from October 2018 to October 2019, Dr. Cammarata-Mouchtouris' objective was to explore the epigenetic control of NF-κB target genes expression. The NF-κB transcriptional selectivity is at the core of the innate immune response regulation. The aim was to crack the “inflammatory chromatin code” that selectivity is based on.

Post-doc biography - Layale Salem-Wehber

Laboratory for Innate Immune Response in Insect Models (M3I), Institute for Molecular and Cellular Biology (IBMC), University of Strasbourg and CNRS

Layale Salem-Wehber

Layale Salem-Wehber's first steps in science commenced with a Bachelor’s degree in Life sciences from the Lebanese University in 2014. After three years of extensive theoretical studies in this field, she decided to deepen her knowledge on the cellular and molecular aspect of biology. In order to achieve this, she joined the master’s in functional genomic and proteomics at Saint Joseph’s University (USJ), Lebanon. During the final semester, she was part of a collaborative internship under the supervision of Dr. Laure El Chamy from USJ and Dr. Nicolas Matt at IBMC, Strasbourg University.

After the internship, she received a fellowship from the doctoral school ED414 in Strasbourg to begin a PhD in co-tutorship between USJ and IBMC. During her PhD, she explored novel regulatory processes that ensure the proper modulation of the highly conserved NF-kB signaling pathways using the Drosophila model. Her results, submitted for publication, showed that the NF-κB pathway, IMD, is tightly regulated at multiple levels by protein phosphatases. It also allowed her to develop skills in scientific research and gain the objective to further deepen knowledge in genetics and immunology. Layale Salem-Wehber joined the laboratory of Dr. Nicolas Matt in December 2019 as a post-doctoral researcher, to work on the USIAS project with the motivation to decipher the mechanisms regulating immune responses, both in insects and mammals.

Links

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