Molecules to Behaviour
Laboratory of Molecular Neurobiology and Behaviour
Why do we get sleepy at night? Why do we get hungry at lunch time? How do we anticipate different events in our surroundings?
Understanding how the brain works is one of the biggest endeavours in biological research. We approach this problem using Drosophila melanogaster and circadian behaviour as a model, at the intersection of biochemistry, neurobiology and behavioural sciences.
Location
Medical Sciences Building, University of Alberta
T6G 2H7
Contact Info
toplab.fly@gmail.com
Tel +1 780 492 7787
LEArn more
Circadian behaviour is an ideal model for understanding how the brain works because it is a collection of anticipatory behaviours that are hard-wired into the brain: an animal can anticipate sunrise and wake up at approximately the same time every day. By studying this innate behaviour, we avoid the complexities that learned behaviour can create.
Time-dependent anticipatory behaviours are collectively called circadian behaviours. Circadian behaviours are regulated by a transcription/translation negative feedback loop called the “circadian clock” or “molecular clock”. Like a clock that we all recognize, the circadian clock keeps biological time and ensures that the body is synchronised, regulating its physiology and ultimately behaviour. The basic architecture of the circadian clock is conserved across almost all species. In Drosophila, the core of the circadian clock is comprised of two transcriptional activator proteins called Clock and Cycle (CLK and CYC) and two transcriptional inhibitors called Period and Timeless (PER and TIM). The CLK/CYC complex activate the transcription of hundreds of genes, including PER and TIM. After accumulating in the nucleus, the PER/TIM complex repress CLK/CYC transcriptional activity, closing the negative feedback loop. Mechanistic delays built into the negative feedback loop ensure an approximate 24-hour oscillation of genetic expression.
Mutating any of the circadian proteins causes the 24-hour rhythm to deviate. The “perceived day” of the animal could become as short as 16 hours and as long as 32 hours. Mutations can also cause “arrhythmic” behaviour, whereby animals can no longer synchronize their body physiology with planetary rhythms, despite environmental cues (e.g. day and night cycles). Such mutations can interfere with the animal’s physiology and anticipatory behaviour.
From Molecules to behaviour
We noticed that targeted mutation of behaviour genes (in our case, circadian genes) can cause a loss of gene function in some neuronal clusters, but have no effect in other neuronal clusters within the same brain. In other words, a mutant gene can appear to function like the wild-type variant, if they are expressed in the relevant region of the brain. This suggests that the function of a behaviour gene is dependent on distinct molecular mechanisms in the different regions of the brain.
To understand behaviour at molecular resolution, we aim to uncover the distinct molecular mechanisms that regulate behaviour. We believe that our work will (1) offer valuable target sites for small molecule intervention to develop drug therapies for various forms of neurodegenerative disorders, some behavioural disorders and mental illness; (2) inform us of genetic diseases that affect the well-being of our society.
Contact
Questions? Shoot us a message!
* required field