Understanding the rules of life

Bioscience for sustainable agriculture and food

Bioscience for an integrated understanding of health

Category: Standard Studentships

Genetic and molecular analysis of the ‘evening state’ of the circadian clock in the model organism Drosophila melanogaster

Primary Supervisor

Dr Herman Wijnen – University of Southampton

Co-Supervisor(s)

Professor Claudio Alonso – University of Sussex

Summary

Both insects and mammals organise their physiology and behaviour in a coherent daily schedule that is controlled by a conserved internal mechanism for daily timekeeping known as the circadian clock.

Due to its pervasive impact on bodily functions, the circadian clock impacts many aspects of human and animal health and well-being.  The fruit fly Drosophila melanogaster has been established as a particularly powerful genetic model for understanding molecular and neural mechanisms underlying circadian clock function. Previous work has demonstrated that different subsets of clock-bearing neurons take responsibility for directing sleep/wake rhythms under light versus dark conditions. The neuronal signalling mechanisms underlying rhythmic behaviour in constant dark, representing a clock state in anticipation of dawn, are relatively well-characterized. However, this is not yet the case for conditions where rhythmic behaviour occurs in the continuous presence of light, representing anticipation of dusk. This project aims to elucidate signalling mechanisms that establish ‘the evening state’ of the circadian clock. This will be achieved via analyses of (1) molecular clock function in the evening pacemaker neurons (‘e cells’) and (2) output pathways connecting ‘e cells’ to sleep/wake rhythms. The PhD student will experimentally address these objectives by taking advantage of the powerful genetic tools available in Drosophila to conduct spatiotemporally-targeted genetic screens aimed at identifying microRNAs and protein coding genes that act in ‘e cells’ or relevant downstream neurons to impact sleep/wake rhythms in constant red light conditions. Mutant genotypes that disrupt sleep/wake rhythms in constant red light will be further classified based on their impact in other environmental contexts as well as their impact on molecular circadian rhythms in different subsets of clock neurons and non-neural tissues. Finally, genetic and molecular interaction studies will be conducted to trace the signalling mechanisms underpinning timekeeping during the ‘evening state’ of the clock.