Description du projet
Contrôle circadien des leucocytes
L’horloge circadienne joue un rôle essentiel dans la régulation des rythmes quotidiens de divers processus physiologiques, comportementaux et moléculaires. Elle permet aux organismes de s’adapter efficacement aux changements environnementaux. L’une des fonctions importantes de l’horloge circadienne consiste à synchroniser et de coordonner les activités du système immunitaire, à la fois dans des conditions normales et en réponse à des infections. Financé par le Conseil européen de la recherche, le projet CIRCODE se concentre sur les leucocytes, composants clés du système immunitaire, et sur leurs schémas de migration dans l’organisme sur une période de 24 heures. Les chercheurs étudieront les mécanismes moléculaires qui sous-tendent ces rythmes régissant le mouvement des leucocytes vers des organes spécifiques. Les résultats fourniront des informations précieuses sur le contrôle du système immunitaire dans un contexte de santé et de maladie.
Objectif
Leukocytes are the key components of the immune system that fight infections and provide tissue repair, yet their migration patterns throughout the body over the course of a day are completely unknown. Circadian, ~24 hour rhythms are emerging as important novel regulators of immune cell migration and function, which impacts inflammatory diseases such as myocardial infarction and sepsis. Altering leukocyte tissue infiltration and activation at the proper times provides an option for therapy that would maximize the clinical impact of drugs and vaccinations and minimize side effects.
We aim to create a four-dimensional map of leukocyte migration to organs in time and space and investigate with epigenetics techniques the molecular mechanisms that regulate cell-type specific rhythms. We will functionally define the daily oscillating molecular signature(s) of leukocytes and endothelial cells with novel proteomics approaches and thus identify a circadian traffic code that dictates the rhythmic migration of leukocyte subsets to specific organs under steady-state and inflammatory conditions with pharmacological and genetic tools. We will assess the impact of lineage-specific arrhythmicities on immune homeostasis and leukocyte trafficking using an innovative combination of novel genetic tools. Based on these data we will create a model predicting circadian leukocyte migration to tissues.
The project combines the disciplines of immunology and chronobiology by obtaining unprecedented information in time and space of circadian leukocyte trafficking and investigating how immune-cell specific oscillations are generated at the molecular level, which is of broad impact for both fields. Our extensive experience in the rhythmic control of the immune system makes us well poised to characterize the molecular components that orchestrate circadian leukocyte distribution across the body.
Champ scientifique
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomics
- medical and health scienceshealth sciencesinflammatory diseases
- medical and health sciencesbasic medicineimmunologyimmunisation
- medical and health sciencesbasic medicinephysiologyhomeostasis
- natural sciencesbiological sciencesgeneticsepigenetics
Programme(s)
Thème(s)
Régime de financement
ERC-STG - Starting GrantInstitution d’accueil
80539 Muenchen
Allemagne