The circadian clock in macrophages: Mechanisms and pathophysiological implications

• Applicant: Dr. Bert Maier
• Subject Area: Cell Biology
• Term: from 2010 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 186269862

Time of day-dependent variations of immune system parameters are ubiquitous phenomena in immu-nology. While the circadian clock has been attributed to coordinate these variations on multiple levels, their molecular basis is little understood. In mammals the circadian system is organized in a hierar-chical manner. The suprachiasmatic nuclei (SCN) generate and integrate time information and send them to peripheral organs. There, like in the SCN, molecular clockworks are responsible for rhythm generation. These peripheral clocks modulate tissue physiology locally. Our goal is to unravel the molecular basis and the biological implications of a circadian regulation of immune functions. By using a candidate approach based on circadian profiles of the macrophage transcriptome we aim to identify rate limiting circadian components in the immune regulatory cascade of an LPS triggered cytokine response. Furthermore, conditional clock knockout and adoptive transfer mouse models will be used to dissect the role of systemic versus local time information in the circadian regulation of the pathophysiology of endotoxic shock.Macrophages are key regulators in a broad spectrum of physiological and pathological processes such as immune responses, autoimmune diseases, tumor growth and metabolic imbalance. Mecha-nistic insights in the circadian regulation of macrophages’ physiology will likely impact on diagnosis and treatment of many diseases.

• DFG Programme: Research Grants