Vertebrates are constantly subjected to threats arising from their living environment. To survive, they have evolved a highly complex immune system that can recognize a myriad of danger signals issued upon invasion by foreign organisms or produced endogenously during the onset of a pathology. While the immune system is instrumental to eliminate these threats, an exacerbated immune response can lead to excessive inflammation, tissue damage and eventually diseases.
Understanding how the cellular and molecular effectors of the immune system recognize these threats, how immune cells are reprogrammed to efficiently fight the danger, and how this fighting may be controlled not to harm the host, are the major questions our team tries to address. To meet these challenges, our team has set up a multiscale approach, ranging from studies at the molecular level based on biochemical and structural methodologies, to investigations in a whole organism, the zebrafish, using live imaging.
News
March 2022 - Audrey Bernut receives the Michel Chignard Prize from the French association Vaincre La Mucoviscidose.
"The Michel Chignard Prize rewards a young researcher or teacher-researcher who has distinguished himself/herself both for his/her scientific excellence in the field of cystic fibrosis and for his/her educational qualities."
Dec
ember 2021 - Welcome to Audrey Bernut who joins our team as CNRS CR Researcher!
September 2021 - Welcome to our 3 new PhD students from the MSCA-ITN European network INFLANET: Liz, Maria and Resul!
Theme 1: Immune cell activation
Theme leaders : Dr. Georges LUTFALLA and Dr. Mai NGUYEN CHI
Innate immunity is at the front line to thwart microorganism invasion. The zebrafish has proven particularly suitable for studying immune response to infections and injury. Thanks to the genetic amenability and transparency of its larvae and embryos, it provides an outstanding opportunity to decipher the dynamics of immune cell activation in infected and damaged tissues.
Our group uses the zebrafish larvae to unravel how phagocytes differentiate and fight microbes.
Theme 2: Danger signals and chronic inflammation
Theme leader : Dr. Laure YATIME
We are interested in the molecular actors of the innate immune system whose excessive activation by pathogenic or endogenous danger signals causes chronic inflammation related to human pathologies such as hemolytic diseases, inflammatory bowel diseases or cancers. Our current work aims to understand how the recognition of these danger signals by specific immune receptors generates a pro-inflammatory response promoting the progression of these pathologies. To this purpose, we use a multidisciplinary approach combining biochemistry, cell biology, structural biology and in vivo modeling in zebrafish.
Theme 3: Antibacterial defenses and inflammation during cystic fibrosis
Theme leader : Dr. Audrey BERNUT
Theme 4: Lymphopoiesis
Theme leader : Dr. Paul GUGLIELMI
1 / the primitive hematopoiesis, which originates at 2 jpf from hemogenic buds on the surface of the yolk sac;
2 / the classical hematopoiesis, dependent on conventional stem cells and taking place first in the caudal hematopoietic tissue, then in the cephalic kidney.
We complete our imaging work by analyzing the transcriptome of B cells during their maturation. Our aim is to develop analysis protocols on isolated individual cells. An analysis of the antibody repertoire by RNA-Seq completes this study.
Theme 5: Intron dynamics
Theme leaders : Dr. Georges LUTFALLA and Dr. Clement METTLING
Introns are a hallmark of metazoan genes, but their role in the evolution of genomes is still of debate: Selfish? exon shuffling? Their conservation in most species proves their extreme stability. The existence of independent and distant species not obeying this rule proves that introns can move and suggests that metazoans with introns possess an active mechanism to prevent this dynamics.
According to Walter Gilbert's theory, introns are lost by homologous recombination with reverse transcribed cDNAs. To further assess this hypothesis, we study genome dynamics in a mouse model that accumulates reverse-transcription products and promotes homologous recombination.
BEGON-PESCIA Christina
BERNUT Audrey
DEMOU Maria
HERNANDEZ PEREZ Liz
LEIBA Jade
OZBILGIC Resul
PARIS Théo
Head of the Team
Georges LUTFALLA
Research Director (DR1) CNRS
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Immune cell activation
(Mai Nguyen-Chi / Georges Lutfalla)
Danger signals and chronic inflammation
(Laure Yatime)
Lymphopoiesis
(Paul Guglielmi)
Intron dynamics
(Clément Mettling / Georges Lutfalla)
