Regulation of brain fluid homeostasis by dynamic aquaporin-4 subcellular relocalisation

Background:

Aquaporins facilitate passive, bidirectional water transport in all cells and tissues. In the brain and spinal cord, aquaporin-4 facilitates the exchange of water across the blood-spinal cord and blood-brain barriers, controlling cell volume, extracellular space volume and astrocyte migration. Recently, we have demonstrated that aquaporin-4 localisation is dynamically regulated at the subcellular level, affecting membrane water permeability. In animal models of ageing, stroke, traumatic injury and sleep disruption, all risk factors for neurodegeneration, both glymphatic function and aquaporin-4 perivascular localisation are reduced. Brain and spinal cord oedema are caused by the influx of water through aquaporin-4 following insults such as traumatic injury, stroke or cancer. We have demonstrated that reducing dynamic subcellular relocalisation of aquaporin-4 to the blood-spinal cord or blood-brain barriers reduces oedema and accelerates functional recovery in rodent injury models. Targeting dynamic aquaporin-4 subcellular relocalisation provides a novel approach to modulating aquaporin-4 function for clinical benefit.

Objective:

This PhD project aims to understand how aquaporin-4 localisation is regulated in health and disease using in vitro and/or in vivo methods. We will use a suite of cutting-edge biochemical and biophysical approaches to characterise this regulation.

The long-term impacts of this project will be the identification of a mechanistic framework to understand the fundamental physiological process of brain water homeostasis and the use of this knowledge to prevent brain swelling and neurodegeneration, contributing to an urgent and unmet clinical need for new effective medicines.

Key Papers:

Salman MM et al. Emerging roles for dynamic aquaporin-4 subcellular relocalization in CNS water homeostasis, Brain, 2022, 145, 64-75 (Featured on the front cover).

Salman MM, Kitchen P, Yool AJ and Bill RM: Recent breakthroughs and future directions in drugging aquaporins, Trends Pharmacol Sci, 2022, 43,30-42 (Featured on the front cover).

Kitchen P et al.: Targeting aquaporin-4 subcellular localization to treat central nervous system edema, Cell, 2020, 181, 784-799.

Supervisors:

Dr. Philip Kitchen

Prof. Roslyn Bill

PhD programmes are for those who are seeking to develop greater in-depth knowledge in a specific area. Completing this level of study is about making an original contribution to knowledge, making new discoveries and developing lifelong skills. 

At Aston University, our Engineering and Physical Sciences PhD programmes will provide all the support and facilities you will need to develop into a leading researcher in your chosen field.  You will be welcomed into a supportive community with a shared enthusiasm for original research, where diversity and multidisciplinary is championed.

Person Specification

Candidates should have been awarded, or expect to achieve, EITHER:

• A Bachelors degree in a relevant subject with an award of First Class or 2.1. 

OR 

• A Bachelors degree in a relevant subject with an award of First Class or 2.1, and a Masters degree in a relevant subject with an award of Merit or higher.

Qualifications from other countries which are considered by Aston University to be equivalent to that described above will be eligible to apply.

Submitting an application

We can only consider applications that are complete and have all supporting documents. Applications that do not provide all the relevant documents will be automatically rejected. Your application must include: 

1. English language copies of the transcripts and certificates for all your higher education degrees, including any Bachelor degrees.
    
2. A Research Statement detailing your understanding of the research area, how you would approach the project, and a brief review of relevant literature. Be sure to use the title of the research project you are applying for. There is no set format or word count. 
    
3. A personal statement which outlines any further information which you think is relevant to your application, such as your personal suitability for research, career aspirations, possible future research interests, and further description of relevant employment experience. 
    
4. Two academic referees who can discuss your suitability for independent research. References must be on headed paper, signed, and dated no more than 2 years old. At least one reference should be from your most recent University. You can submit your references at a later date if necessary. 
    
5. Evidence that you meet the English Language requirements. If you do not currently meet the language requirements, you can submit this at a later stage. 
    
6. A copy of your passport. Where relevant, include evidence of settled or pre-settled status.

Interviews

Interviews will be conducted online via Microsoft Teams. If you are shortlisted, you will be contacted directly with details of the interview.  

Studying a PhD is great route into academia and industries that are centred on research and innovation. Areas with a demand for very high level and specialised research skills often demand PhDs.

In addition to this specialist knowledge, PhD education will help you to develop a set of valuable transferrable skills. The very nature of studying an intensive research degree will enable you to become a team player, develop problem-solving skills, analytical thinking, and advanced presentation and communication skills.

The variety of PhD project topics at Aston means that the destinations of our graduates vary substantially. Some choose to continue into academia, at either Aston or other leading institutions, while others go onto use their newly acquired skills in a range of research, healthcare, industry or charitable fields. When selecting your chosen PhD path at Aston, your supervisor will be able to provide you with relevant career opportunities that could be available to you in your specialist area.