Project description
Circadian control of leukocytes
The circadian clock plays a vital role in regulating daily rhythms in various physiological, behavioural and molecular processes. It allows organisms to adjust to environmental changes effectively. One important function of the circadian clock is to synchronise and coordinate immune system activities, both under normal conditions and in response to infections. Funded by the European Research Council, the CIRCODE project focuses on leukocytes, key components of the immune system, and their migration patterns throughout the body over a 24-hour period. Researchers will investigate the molecular mechanisms behind these rhythms that govern leukocyte movement to specific organs. Findings will provide valuable insights into immune system control in health and disease.
Objective
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.
Fields of science
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomics
- medical and health scienceshealth sciencesinflammatory diseases
- medical and health sciencesbasic medicineimmunologyimmunisation
- medical and health sciencesbasic medicinephysiologyhomeostasis
- natural sciencesbiological sciencesgeneticsepigenetics
Programme(s)
Topic(s)
Funding Scheme
ERC-STG - Starting GrantHost institution
80539 MUNCHEN
Germany