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The potential of Drosophila circadian clock circuits to model neurodegenerative conditions.

Biology Colloquium | Prof. Sheeba Vasu | Nov 24th, 2023 (Friday)

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Circadian clocks are endogenous mechanisms that modulate the daily rhythm of cellular and behavioural phenomena in living organisms.  There is growing awareness that disruptions to functioning of the circadian clock can impinge on human health span. In the context of neurodegeneration there is evidence from clinical and laboratory studies which indicate bidirectional modulation of clocks and neuronal health. I will present some of our recent studies using the model organism Drosophila melanogaster, which indicate that strengthening circadian rhythms may be a viable therapeutic alternative to mitigating the toxic effects of neurodegenerative agents such as the polyglutamine expansion containing Huntingtin protein.

Summary of research activities:
Sheeba Vasu’s research tackles two important and distinct aspects of circadian clocks – their evolution and underlying neuronal circuitry.  Having established a unique set of populations subjected to long-term selection under naturalistic environments, she demonstrated the evolution of circadian clock properties and life-history traits. She showed that the evolution of extremely ‘early’ and ‘late’ chronotypes is accompanied by altered circadian clock organization, including heightened temperature sensitivity in the ‘late’ chronotypes. She provided the first-ever demonstration of the evolution of a non-clock phenomenon – ‘masking’ in the ‘early’ chronotypes. She demonstrated that cyclic food availability was not a time cue to the central brain clock and provided the first high-resolution day-night profile of the fly metabolome. Employing genetic manipulations in Drosophila melanogaster, her studies suggest that a circadian neuropeptide signals to sleep centres via its cognate receptors. Her studies were the first to suggest a role for gap-junction proteins -Innexins, in modulating fly circadian rhythms. She demonstrated the role of temperature-sensitive ion channel dTRPA1 in mediating rhythmic locomotion and revealed that a circadian neuropeptide pigment-dispersing factor suppresses nighttime activity under continuously warm days.  She and her collaborators elucidated the neuronal circuitry by which gentle, repetitive, mechanical stimulation can induce sleep in flies through mechanosensory Nanchung-expressing neurons. Another collaborative effort has revealed that the fly circadian circuit can serve as a model to understand cellular processes that mediate neurodegeneration and suggest possible pathways that can be targeted for therapeutic intervention.

About the Speaker: 

Prof. Sheeba Vasu graduated with a M.Sc. from  Mangalore University in 1996 . She then obtained her PhD  from  Jawaharlal Nehru Centre for Advanced Scientific Research in 2002 . She is currently Professor at  Jawaharlal Nehru Centre for Advanced Scientific Research. She has previously worked at several renowned universities including University of California, New York University and University of Massachusetts. She is the recipient of numerous awards. Her pioneering work  has led to close to several peer-reviewed publications in top journals and book chapters.

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