Circadian clock regulatory mechanisms and the etiology of behavioural disorders

Approximately one in three Canadians experience a mental illness like depression in their lifetime, which costs Canadian society $51 billion every year. Current drugs are not always effective and can have unwanted side effects. We need better treatments with fewer side effects. To develop these treatments, we first need to understand how mental illnesses happen. We use fruit flies to study the effects of mental illness on the brain. Sleep-wake cycles, or circadian rhythms, are controlled by coordinating functions of different parts of the brain. Some people with mental illnesses have mutations in genes controlling these sleep-wake cycles. We plan to learn how these mutations cause mental illness. We discovered that mutations in some sleep-wake cycle genes disrupt some parts of the brain, but not other parts. This causes different parts of the brain to cycle at different rates, disrupting the whole brain. We believe that this may be one way in which mental illnesses develop. We will study this problem three ways. (1) We will study how gene mutations change the function of the gene, and how other proteins in brain cells act on the gene. (2) We will then study how these mutations affect the function of different brain cells. (3) We will use what we have learned to understand why so many mutations in genes that are connected with mental illnesses cause changes in behaviours, like sleep, fighting, eating and memory. (4) We will artificially change different parts of the brain to see if we can cause the same change in behaviours as mutations. Overall, we will study the molecules, the brain cells and the behaviours to gain a complete picture of how mutations in circadian genes cause mental illnesses.