Comparative study of circadian behaviours of Drosophilid species

 

The fruitfly Drosophila melanogaster has proven to be a model to understand circadian organization at the behavioural, neuronal and genetic levels. Although several hypotheses have been proposed to explain how circadian neurons regulate specific aspects of rhythmic behaviour based on this model, much remains to be understood regarding the functional significance of circadian activity/rest patterns. In an attempt to address the question of functional significance of circadian organization using a comparative approach we aim to compare several aspects of activity/rest rhythm under various environmental cycles along with natural conditions, neuronal architecture and cycling of various clock proteins in these neurons of wild-caught D. melanogaster and some of its close relatives.

Drosophila circadian model to study Huntington's disease

 

Our main aim is to study the cellular and molecular mechanisms involved in neurodegenerative disease progression using Drosophila melanogaster circadian system as a model. The Drosophila circadian organisation due to its robust behavioural readout and genetic tractability provides an ideal system to simultaneously track and study behaviour and the underlying neuronal circuits that control them. Specifically, we are trying to address several questions surrounding Huntington’s Disease such as selective susceptibility of some neuronal subtypes versus others to the presence of mutant Huntingtin, the role of aggregates in disease progression and also chart the time-course of association between cellular dysfunction and behaviour. We use a combination of genetic, behavioural and immuno-histochemical approaches in our studies.

Thermoreceptors and temperature entrainment in Drosophila melanogaster

 

How organisms respond to their environment has been a subject of great scrutiny. Circadian clocks help organisms to synchronize their physiological and metabolic activities with the external fluctuating environment in order to maximise their chances of survival. While our understanding of how light/dark cues are utilised by circadian clocks to gain temporal information has advanced greatly, we are yet to fully comprehend the mechanism of temperature entrainment of circadian clocks. We are interested in characterising the role of various thermoreceptors in conveying thermal inputs to the circadian clock, using genetically tractable model system Drosophila melanogaster. We probed the role of heat sensitive ion channel, dTRPA1 (drosophila Transient Receptor Potential A1), in temperature entrainment pathways. Our studies suggest that there are several possible communication routes between dTRPA1 and circadian clock neurons. Functional level of dTRPA1 expression is of critical importance to flies when subjected to an environmental regime of temperature cycles in constant darkness. dTRPA1 null mutants or flies with RNAi downregulation of dTRPA1 phase their locomotor activity/rest rhythms differently from wild type control flies. Further, we also observed altered neuronal firing of dTRPA1 neurons can affect phase of locomotor rhythms under light/dark cycles at different constant temperatures.

Sleep regulation in Drosophila melanogaster

 

Sleep in Drosophila is a well-established behaviour and like in most organisms, involves circadian regulation and homeostatic control. While the circadian clock circuitry is well-understood, so far no specific region has been identified as the sleep homeostat. Thus, identifying such a region, and establishing its subsequent circuitry is important for a better insight into understanding sleep regulation. A number of neuronal circuits have been implicated in sleep regulation – arousal-promoting circadian clock neurons large ventral lateral neurons (l-LNv), sleep-promoting dorsal fan-shaped body (FB), learning and memory centre mushroom body (MB) and neuroendocrine centre Pars Intercerebralis (PI). However how these interact to bring about the overt behavior is unknown, and joining the dots of this seemingly dissociated circuit is another one of our aims. Apart from these, we are also probing the significance of sleep by examining the effects of sleep loss on fitness-related traits in Drosophila.

Circadian rhythms in natural conditions in Drosophila melanogaster

 

Although lab-based studies have given us tremendous insight into the oscillator properties of circadian clock entrainment to time-cues, we know very little about how organisms synchronize their clocks in the real world, where multiple environmental factors change simultaneously and gradually. This study includes understanding the role of light and temperature in bringing about salient features of circadian rhythms under semi-natural conditions. This involves recording activity-rest and eclosion rhythms under semi-natural conditions and following up and validating that with simulated natural-like protocols in the lab. We also examine the behavioral significance of the three activity peaks seen under nature, through obtaining chronoethograms of grouped and solitary flies.

Circadian clocks and metabolism in Drosophila melanogaster

 

This project deals with understanding the interaction between circadian clocks and body metabolism and its influence on the physiological well being of organisms. Studies have reported daily cycling of a wide variety of metabolites involved in some of the central pathways of energy homeostasis, slight deviations in which may reflect irregularities in physiology of organisms. We use an approach to look at the temporal profiles of body metabolites which are likely to reflect the physiological state of the organism. In addition, we are also trying to understanding how food intake can affect circadian clocks, especially in terms of its role as a time cue. Feeding rhythms are also under the control of circadian clocks, and understanding the complex network of feeding, metabolism and circadian behaivours forms the basis of this project.