Identification of distinct regulatory mechanisms of circadian transcription programs across the circadian neuronal network.

Behavioural disorders are linked to circadian rhythm disruption. Circadian rhythms are behavioural responses to daily environmental changes, like light/dark cycles. Such behavioural responses are regulated by circadian clocks, which are biochemical time keeping machines that control the daily expression of several hundred genes. There is a circadian clock hypothesis of behavioural disorders that offers a framework to understand behavioural disorders, but how they are linked to each other is unknown.

Mutations in circadian clocks that cause behaviour problems also cause the several hundred circadian-regulated genes to oscillate with different amplitudes, phases and periods in different brain cells. This means that the oscillating genes become uncoupled from each other, because the oscillations all look different. We think that this uncoupling causes behaviour disorders. For a single mutation to cause such differences in gene expression can only be explained by differences in the regulatory proteins made in different brain cells. We will identify the regulatory proteins that act on the circadian clock in the different brain cells using unique methods that we developed. Once we identify the regulatory proteins in different brain regions, we have an opportunity to intervene with these proteins to realign uncoupled gene oscillations, hoping to restore behavioural disorders.

Faculty Supervisor:

Deniz Top

Student:

Partner:

Radboud University Nijmegen

Discipline:

Life Sciences

Sector:

Education

University:

University of Alberta

Program: