Grant: CIHR New Investigator

Sleep and circadian rhythms (24-hour biological rhythms regulated by an internal biological clock) have a huge impact on human performance and biology. However, our knowledge of the genes influencing human sleep and circadian biology is incomplete. Moreover, while small-scale animal and human experiments suggest that sleep and circadian disruption (as experienced, for instance, in shift-work and jet-lag) may have a major impact on brain function, their impact on neurological disease at the population level is only partly understood. The overall goal of the applicant's research plan is to identify genes influencing human sleep and circadian function, and to explore the impact of sleep and circadian disruption on common and important human brain diseases in aging such as dementia and stroke. Toward this end, the applicant has developed a number of analytical approaches to facilitate large-scale at home measurement of sleep and circadian rhythms, and to measure brain genetic rhythms from collections of brain tissue obtained from organ donors. He will apply these tools to several large existing studies in Canada and the United States, as well as to an existing collection of donated brain tissue to identify genes influencing human sleep and circadian rhythms and the mechanisms whereby they act, and to assess the influence of sleep and circadian disruption on human brain diseases in the community. This work may lay the foundation for new treatments to manipulate sleep and circadian function to combat the adverse brain effects of jet lag or shift work as experienced by millions of Canadians. It may also lead to genetically guided optimization of the scheduling of neurological therapies to optimize clinical outcomes. Finally, it may lay the foundation for sleep or circadian interventions as a potential strategy for decreasing the burden of stroke, dementia, and other brain disorders in the aging Canadian society.