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. 40-70% of old people experience chronic circadian and sleep disturbances with Parkinson and Alzheimer’s disease causing more pronounced circadian and sleep deficits, with poor sleep contributing to disease pathology.
We have shown clock neurons show activity rhythms with higher firing rates and more depolarized membrane potentials during the day in both flies and mice. However, the mechanisms driving day/night differences clock excitability are not understood. We have 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, interdisciplinary and strategically relevant PhD project, the candidate will be trained to 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: 1. To determine which potassium channels underlie the clock neuron membrane properties changed by ageing a. Determine the potassium channel mediated changes that switch clock neurons between day/night activity b. 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.
How to apply
To apply, please read the information on the prospectus page of the programme - South West Biosciences Doctoral Training Partnership (BBSRC) | Study at Bristol | University of Bristol, including the Admissions Statement and the English proficiency requirements.
Then, enter the University of Bristol application portal: Start your application | Study at Bristol | University of Bristol and select the programme “South West Biosciences Doctoral Training Partnership (PhD)”.
You can select any of the entry points, applying to up to 3 projects, although the start date will be in September 2024. You can select any of the entry points, applying to up to 3 projects, although the start date will be in September 2024.
The application deadline is 11:59 pm on 04/12/2023.
You can find more information at the link: How to apply – SWBiosciences Doctoral Training Partnership, selecting “University of Bristol”.
The South West Biosciences Doctoral Training Partnership (SWBio DTP) is led by the University of Bristol, together with the Universities of Bath, Cardiff and Exeter, alongside Rothamsted Research. This partnership also includes the following associate partners; Marine Biological Association (MBA), Plymouth Marine Laboratory (PML), SETsquared Bristol, Swansea University, UCB Pharma and University of the West of England (UWE).
These institutions represent a distinctive group of bioscience research staff and students, with established international, national and regional networks, and widely recognised research excellence. As research leaders, we have a strong track record in advancing knowledge through high-quality research and teaching, in partnership with industry and the government.
The programme particularly aims to provide students with outstanding interdisciplinary research training within the following areas - advancing the frontiers of bioscience discovery; bioscience for sustainable agriculture and food; bioscience for an integrated understanding of health. Importantly this research training is also underpinned by transformative technologies, allowing our students to expand the boundaries of their research through innovative tools, technologies and approaches. Our students will be exposed to the expertise of all the partners by visiting / using their facilities, taking part in joint conferences, workshops and taught modules. To further the collaboration between the partnership, cross-institutional PhD projects will be featured that build on the expertise of each partner.
Programme – SWBiosciences Doctoral Training Partnership
If you have any questions on the scheme, you are welcome to contact Sue Summerill (Graduate Administration Manager, Faculty of Life Sciences) with any questions - [Email Address Removed].
For project-related enquiries, please contact the project supervisor.