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Modelling the effect of ageing on Drosophila and mouse clockneurons

Project Description

All organisms are subject to daily environmental changes caused by the earth’s rotation leading to the evolution of circadian clock mechanisms that regulate changes in behaviour, physiology and metabolism across the day to ensure their timely occurrence and allowing environmental adaption. The central circadian clock maintains a ~24-hour rhythm and consists of clock neurons that express a molecular oscillator that cycles every 24-hours by a mechanism conserved from Drosophila to mammals including humans. Circadian rhythms are important for health, with misalignment resulting in sleep disorders, depression and cancer. With ever-increasing human lifespans, understanding how circadian rhythms change during ageing is of growing interest and health relevance, with the population aged over 60 years old set to more than double by 2050.

We have shown clock neurons show activity rhythms with higher firing rates and more depolarized membrane potentials during the day than at night. These changes are similar in flies and mice. However, the mechanisms driving day/night differences clock excitability are not understood. We have also shown that ageing disrupts circadian rhythms, sleep and clock neuron excitability in flies with similar effects in aged mice, again by unknown mechanisms. In this collaborative PhD project, the candidate will be trained in and then perform a combination of electrophysiology, pharmacology,genetics, imaging, behaviour and computational modelling, to identify which clock neuron expressed potassium channels underlie the day/night differences in membrane excitability and how these are changed by ageing. The overall aim of this collaborative studentship is to test the hypothesis that ageing changes the potassium channel mediated membrane properties of clock neurons, which will be investigated through the following objectives:

Objective 1: Which potassium channels underlie the clock neuron membrane properties changed by ageing?

1A: Determine the potassium channel mediated changes that switch clock neurons between day/night activity

1B: Develop a model of day/night differences in clock neuron excitability and test if the proposed potassium channel changes switch the
neurons between day/night

2A: Determine how ageing affects potassium channel mediated changes in clock neuron excitability

2B: Develop a model of the effect of ageing on clock neuron excitability and test if the proposed potassium channel mediated change can
switch the neurons between young and old

2C: Compare Drosophila and mammalian models of day/night differences in clock neuron excitability and ageing

Key words: Drosophila, electrophysiology, computational modelling, circadian rhythms, ageing

Funding Notes

This project is available under the SWBio DTP programme: Link to SWBio DTP website: View Website

PLEASE ENSURE you select the Faculty of Life Sciences and the programme, South West Biosciences Doctoral Training Partnership_(PhD)

Information on eligibility: View Website

DEADLINE FOR APPLICATIONS: Midnight Monday 2 December 2019
How to apply: View Website

How good is research at University of Bristol in Biological Sciences?

FTE Category A staff submitted: 64.60

Research output data provided by the Research Excellence Framework (REF)

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