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PhD Studentship: How do Aquaporin Water Channels Control Brain Waste Clearance?

Aston University - College of Health and Life Sciences

Qualification Type: PhD
Location: Birmingham
Funding for: UK Students, EU Students, International Students
Funding amount: Funded studentship
Hours: Full Time
Placed On: 15th November 2023
Closes: 4th January 2024

Supervisor: Professor Roslyn Bill

Closing Date: 4th January 2024

Key words: Aquaporins, molecular mechanisms, drug discovery, mechanobiology, protein-protein interactions

Applications are invited for a three-year Postgraduate studentship, supported by the College of Health and Life Sciences to be undertaken within Aston Centre for Membrane Proteins and Lipids Research (https://www.aston.ac.uk/research/hls/ampl) at Aston University. The successful applicant will join an established experimental group working on aquaporin water channels in the central nervous system. The studentship is offered in collaboration with Professor Roslyn Bill’s ERC Advanced Grant, FORTIFY, that investigates how aquaporin water channels control brain waste clearance.

The position is available to start in October 2024.

Financial Support

This studentship includes a fee bursary to cover the home fees rate, plus a maintenance allowance. The maintenance allowance for the academic year 2024/5 is yet to be confirmed, but for reference, the allowance in 2023/4 was £18,622.

Overseas Applicants

Overseas applicants may apply for this studentship but will need to pay the difference between the ‘Home’ and the ‘Overseas’ tuition fees. The fee difference for the academic year 2024/5 is yet to be confirmed, but for reference, the fee difference for 2023/4 was £13,68.

As part of the application, you will be required to confirm that you have secured this additional funding in your personal statement.

Background to the Project

The overall aim of this project is to understand how molecular and biophysical inputs synergistically control dynamic aquaporin-4 subcellular relocalisation, building on our previous published findings (Cell, 2020, 181, 784-799) and the team’s unpublished work. The molecular mechanisms in cultured astrocytes that control AQP4 subcellular relocalisation (protein-protein interactions, mechanistic pathways) including molecular control of mechanosensitive channels will be examined. Approaches will include co-immunoprecipitation and Ni2+-affinity chromatography of endogenous AQP4, transfected AQP4-GFP or AQP4-His6. This approach has already successfully identified that proteins including calmodulin bind AQP4. While we have shown that TRPV4 agonism is necessary and sufficient for AQP4 relocalisation and while AQP4 and TRPV4 have previously been suggested to form a complex, the molecular details of complexation are unknown. This interaction will be explored in detail using a site-directed mutagenesis and co-immunoprecipitation strategy to map the interaction interface. AQP4 subcellular relocalisation will be measured in cells using super-resolution microscopy. This framework will be used to investigate other AQP4 complexes. Use of our unique inhibitor and activator compound library will enable further interrogation of these complexes. Overall, the project will define the AQP4-protein interactions driving brain waste clearance. Future directions will be to use these interactions as explicit targets for drug development.

Person Specification

The successful applicant should have been awarded, or expect to achieve, a Masters degree in a relevant subject with a 60% or higher weighted average, and/or a First or Upper Second Class Honours degree (or an equivalent qualification from an overseas institution) in biosciences, biochemistry or cell biology. Preferred skill requirements include knowledge/experience of cell culture, microscopy, protein chemistry and high-throughput assays. 

Contact information

For formal enquiries about this project contact Professor Roslyn Bill by email at r.m.bill@aston.ac.uk

For details on how to apply, including what documents to include, please click on the 'Apply' button above.

If you require further information about the application process please contact the Postgraduate Admissions team at pgr_admissions@aston.ac.uk

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