Grant: Operating Grant

Circadian (24-hr) rhythms of behaviour and physiology, including sleep-wake cycles and fluctuations in hormones and body temperature, are present in virtually all organisms, and allow them to keep track of, and adapt their needs according to, the time of day. In mammals, these rhythms are driven and maintained by biological clocks throughout the body, including the master circadian pacemaker in the brain, the suprachiasmatic nucleus (SCN), which responds directly to changes in environmental light-dark (day-night) cycles. A set of core "clock genes" expressed in biological clocks represents the machinery that maintains time. The long-term goal of my research is to understand how biological clocks, in particular the SCN clock, are controlled, and how loss of proper control affects the physiology and behaviour of the organism. Recently, we found two novel genes in the mouse SCN that control circadian rhythms: microRNA-132 and UBR4. Both genes are activated by light. While we have data showing that miR-132 affects the ability of the SCN to react to light, virtually nothing is known about the role of UBR4 in biological timing. Thus, our goal here is to understand the functions of miR-132 and UBR4 in the control of circadian rhythms and how they interact with core clock genes to influence the timing process. We would also like to identify specific pathways that link miR-132 and UBR4 to the clock machinery. Since biological clocks affect many aspects of human health and disease (e.g. cancer, mental health disorders, obesity, and cardiovascular diseases), this work will provide new insights into mechanisms that maintain proper functioning of the biological clock and potential causes of circadian dysfunction during disease.