Investigating the Role of Oxysterols in Cholesterol Metabolism and Myelin Maintenance

Cholesterol is a vital lipid that plays a key role in maintaining cellular structure and function, particularly in the central nervous system. A crucial component of myelin - the protective sheath surrounding nerve fibres - cholesterol supports nerve conduction, cell signalling, and overall brain function. However, when cholesterol undergoes oxidation, it forms oxysterols, a diverse group of bioactive molecules with distinct roles in cellular physiology.

This project aims to explore the intricate relationship between oxysterols, cholesterol metabolism, and myelin maintenance. Oxysterols are produced in the body under normal and pathological conditions, particularly in the brain, where they can influence various processes such as lipid homeostasis, inflammation, and cell signalling. Recent studies suggest that oxysterols may play both protective and detrimental roles in myelin, depending on their specific structures and concentrations.

The research will focus on how different oxysterols impact cholesterol metabolism, the synthesis and repair of myelin, and the regulation of neuronal health. The project will use invitro cell culture models to investigate cholesterol metabolism. Using advanced mass spectrometry techniques, project will profile cholesterol d oxysterol pathways. By examining the levels of oxysterols in the context of neurological diseases, such as multiple sclerosis (MS), this project will help uncover how altered cholesterol metabolism and myelin degeneration may contribute to disease progression.

By enhancing our understanding of oxysterols' roles in cholesterol metabolism and myelin biology, this project hopes to contribute to the development of novel approaches for treating demyelinating disorders and advancing overall neurological health.

References 

1. Ana Reis, Irundika H.K. Dias; Oxysterol sulfates in fluids, cells and tissues: how much do we know about their clinical significance, biological relevance and biophysical implications? Essays Biochem 2024; EBC20230090.
2. Borah, K., Rickman, O. J., Voutsina, N., Ampong, I., Gao, D., Baple, E. L., Dias, I. H. K., Crosby, A. H. & Griffiths, H. R. (2020) A quantitative LC-MS/MS method for analysis of mitochondrial -specific oxysterol metabolism, Redox Biol, 101595. PMID: 32574926

Supervisors: 

Dr Irundika Dias

Dr Dan Ma

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's 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.