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Modelling the effect of ageing and Alzheimer disease on sleep and memory in Drosophila


Project Description

Populations are currently aging, as we age a number of processes naturally decline including cognition, this presents a number of societal, healthcare and scientific challenges. One of the most feared aspects of getting old is age-dependent memory impairment (AMI). We have shown the fruitfly, Drosophila like humans display AMI with wildtype flies showing a significant loss of memory after 20 days. A single pair of neurons regulates memory centres in the fly brain that are important for memory consolidation as well as AMI. Recently this highly defined circuit has also been shown to be important for control of sleep. Sleep promotes memory consolidation in humans and flies. Furthermore when humans and flies age their sleep becomes fragmented and shifts from night to daytime sleep.

Furthermore memory and sleep defects are accelerated in Alzheimer’s disease (AD). AD is the most common neurodegenerative condition that is becoming more common due to ageing. AD is associated with amyloid plaques and tau tangles causing neurons to die and patients to have memory and sleep problems. We are taking advantage of the fruitfly’s genetics and rapid ageing to understand how amyloid and tau cause neurodegeneration, memory and sleep problems.

In this PhD project you will be trained in a broad range of Drosophila in vivo and interdisciplinary research techniques aimed at better understanding the interplay between sleep, memory, aging and AD.
These will include:
1) In vivo optogenetic and electrophysiological recordings of the relevant neurons during consolidation, across sleep-wake cycles and through the flies’ lifespan including in AD model flies.
2) Using these measurements of neural activity to generate computational models of the membrane potential and ionic currents that occur during memory consolidation, sleep, aging and AD.
3) These approaches will refine our models generating hypotheses to test by identifying the key membrane signalling events and molecules predicted to switch neurons from naïve to consolidated, from sleep to awake, from young to old and to rescue AD pathology. These will be tested with a range of experimental approaches including measuring predictable changes in behaviour. Ultimately this approach may allow the experimenter to implant memories into the fly without training or optogenetically switch the fly between sleep to wakefulness, between cognitively young and old and AD diseased and wildtype flies.

https://mail.google.com/mail/u/0/#inbox/158263b2065d54d7?projector=1

Funding Notes

This PhD project is open to self-funding students. When applying please do so online at: View Website
Select the Faculty of Biomedical Sciences and the school, School of Physiology and Pharmacology, programme PhD 3 year.

References

[1] Buhl E, Bradlaugh A, Ogueta M, Chen K-F, Stanewsky R and Hodge JJL (2016) Quasimodo mediates daily and acute light effects on Drosophila clock neuron excitability. Proceedings of the National Academy of Science USA: www.pnas.org/cgi/doi/10.1073/pnas.1606547113
[2] Chen C1/Buhl E1, Xu M, Croset V, Rees J, Lilley KS, Benton R, Hodge JJL, Stanewsky R (2015) Drosophila Ionotropic Receptor 25a mediates circadian clock resetting by temperature. Nature 527, 516-520.
[3] Malik BR, Hodge JJL (2014) Drosophila adult olfactory shock learning. Journal of Visual Experimentation 90, e50107.
[4] Cavaliere S, Malik BR, Hodge JJL (2013) KCNQ channels regulate age-related memory impairment. PLoS One 8, e62445.


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