Permanent researcher CNRS
Team B-NATION
My research theme focuses on the role of the regulatory regions of the IgH locus (3’RR and Eµ-MAR) on the 3D organization of the nuclei and on the maintenance of the integrity of the B lymphocyte genome.
Office 107 CBRS
05 19 56 42 04
Research
My research theme is focused on the study of the regulation of immunoglobulin genes in a physiological context in animals (KO and KI murine models). Immunoglobulin genes (IgH and IgL) undergo gene rearrangements during the development of B lymphocytes. These rearrangements (somatic hypermutation and class recombination) are regulated for regulatory elements present on the IgH loci (3’RR and Eµ- Mar) and on the Igk locus (3’Eik). My project aims to dissect the role of these regulatory regions on nuclear organization and on maintaining the genomic integrity of B lymphocytes.
Student supervision
PhD student
Charlotte Bruzeau, University of Limoges.
Thesis topic: Influence of regulatory regions of the immunoglobulin heavy chain (IgH) gene on gene interactions between the IgH gene and the rest of the genome.
Thesis co-supervised with Dr Eric Pinaud, research director CNRS, HDR.
Morgane Thomas, University of Limoges.
Thesis topic: Organization and integrity of the genome of B cells and nuclear matrix proteins.
Thesis co-supervised with Dr Eric Pinaud, research director CNRS, HDR
Ophélie Martin, University of Limoges.
Thesis topic: Somatic hypermutation of normal and pathological B cells: regulatory cis elements and nuclear factors involved
Thesis co-supervised with Dr Eric Pinaud, research director CNRS, HDR
Defense in Octobre 2018
M2R student
Ophélie Martin, Université of Poitiers. 12 weeks in 2015
Topic: Influence of the MAREµ regulatory regions of the IgH locus on the position of AID target genes “off targets” in the germinal center B cells.
Internship co-supervised with Dr Eric Pinaud, research director CNRS, HDR
M1 & engineering school
Loris Verron, ENSTBB Bordeaux. 8 weeks in 2018
Topic: Influence of the Eμ and 3’RR regulatory regions of the heavy chain immunoglobulin (IgH) locus on the maintenance of the organization of the B lymhocyte genome
Valentine Audonnet. ENSTBB Bordeaux. 8 weeks in 2017
Topic: Study of the somatic hypermutation of immunoglobulin heavy chain genes in mouse models deficient for the 3’RR regulatory region.
Christopher Maucourant, Université de Paris 6 – UPMC. 8 weeks in 2015
Topic: Study of the role of the 3’RR regulatory region of the immunoglobulin heavy chain locus by a mouse model showing the replacement of the 3’RR by a micro 3’RR.
Marine Faïsse, University of Limoges. 13 weeks in 2014
Topic: Development of a procedure for calculating distances between cellular objects after reconstitution of 3-dimensional images.
Julian Tronc, University of Limoges. 8 weeks in 2013
Topic: Analysis of the nuclear positioning of the IgH locus and / or its colocalization to heterochromatin by a 3D FISH method on murine B cells.
License and BTS student
Pauline Dupaquier, University of Poitiers. L3 intern. 8 weeks in 2016
Topic: Rôle des différents éléments activateurs composant la région régulatrice en 3’ du locus IgH dans les lymphocytes B sur le positionnement subnucléaire.
Audrey Arquilliere, University of Limoges. L2 discovery internship. 5 weeks in 2015.
Lucie Le Roux, University of Limoges. L2 discovery internship. 8 weeks in 2015.
Ludivine Fini, Legta, Melle. 1st year BTS trainee. 12 weeks in 2014.
Topic: 3D FISH study of the nuclear positioning of the IgH locus in wild and mutant murine B cells.
Charlène Fournier, BTSA ANABIOTEC, La Roque. 1st year BTS trainee. 12 weeks in 2013.
Topic: Standardization of the 3D Immuno-FISH method on murine B cells.
Education
Since 2017 : Permanent researcher CNRS (Section 27). University of Limoges, UMR CNRS 7276, INSERM U1262. Contrôle de la Réponse Immune et des Lymphoproliférations (CRIBL). Team Pr Cogné M.
2012-2017 : post doctoral researcher University of Limoges, CNRS UMR 7276 Contrôle de la Réponse Immune et des Lymphoproliférations (CRIBL). Team Pr Cogné M.
Subject: Role of regulatory regions of the immunoglobulin heavy chain locus (3’RR and MAR) on legitimate and illegitimate recombination events (somatic hypermutation, class recombination and translocation) as well as on the subnuclear localization of immunoglobulin loci
2012:PhD student in biologie. Biology of blood cells. University Paris 7 Diderot – Very honorable mention.
Subject: Analysis of the regulation of early TCR rearrangements in normal thymopoiesis and associated oncogenic abnormalities in acute T lymphoblastic leukemia (T-ALL)
Skills
Molecular biologie: ADN & ARN extraction, PCR, RT/RQ-PCR, LM-PCR, cloning / plasmid construction, sequencing (Sanger and high throughput), 3C/4C (Chromatin Conformation Capture), LAM-HTGTS, RNA-SEQ
Cellular biologie: cell culture (cell lines and murine primary cells), lentiviral infection, transfection of ES cells, Co-culture, sorting of cell subpopulations (ARIA III), system CRISPR/cas 9
Microscopy: Fluorescence In Situ Hybridation (FISH 2D et FISH 3D) and image processing, IF staining
Animal experimentation: Project designer level
Representative publications
Le Noir S, Boyer F, Lecardeur S, Brousse M, Oruc Z, Cook-Moreau J, Denizot Y, Cogné M
Functional anatomy of the immunoglobulin heavy chain 3’ super-enhancer needs not only core enhancer elements but also their unique DNA context
Nucleic Acid Research. 2017 Mar 22.
Le Noir S*, Laffleur B*, Carrion C, Lecardeur C, Garot A, Pinaud E, Denizot Y, Skok J, Cogné M.
The IgH locus 3’ cis-regulatory super-enhancer co-opts AID for allelic transvection
Oncotarget. 2017 Feb 21;8(8):12929-12940.
Laffleur B, Dalloul Z, Dalloul I, Le Noir S, Cogné M.
When immunoglobulin genes assemble with bricks from other chromosomes.
Med Sci 2016 8-9;32(8-9):677-80.
Garot A, Marquet M, Saintamand A, Bender S, Le Noir S, Rouaud P, Carrion C, Oruc Z, Bébin AG , Moreau J, Lebrigand K, Denizot Y , Alt FW, Cogné M, Pinaud E
Sequential activation and Distinct functions for Distal and Proximal modules within the IgH 3’RR region
PNAS. 2016 Feb 9;113(6):1618-23.
Bonaud A*, Lechouane F*, Le Noir S*, Monestier O, Cogné M, Sirac C
Efficient AID targeting of switch regions is not sufficient for optimal class switch recombination
Nature Communication. 2015 Jul 6;6:7613.
Dissemination of scientific culture
Since 2014: Co-Coordinator and animator of an itinerant immuno-fun workshop in Limousin schools
Description: Workshop presented 10 times a year in the 3 departments of Limousin in schools in rural areas, which do not have easy access to science.
Target: 3rd cycle students (CE2, CM1 and CM2).
Funding: Science at school: Promotion of scientific culture in schools. CNRS, INSERM. Partnership foundation of the University of Limoges.
Since 2014: Scientific recreation workshops
Animation of an immuno-fun workshop during CCSTI Limousin recreation Wednesdays.
http://www.recreasciences.com/site/index.php?option=com_content&view=article&id=219&Itemid=175
Since 2014: European researchers’ night.
Since 2013: Science festival.