MRes - Data driven analysis of the potential of cyclodextrin as an Alzheimer's Disease therapeutic using the UK Biobank

Summary

Alzheimer's disease (AD) poses a formidable challenge to aging populations. While complex, the APOE4 gene stands out as the strongest genetic risk factor, significantly increasing an individual's susceptibility. Intriguingly, APOE4's detrimental effects are closely tied to disrupted cholesterol metabolism within the brain. This metabolic link presents a potential therapeutic target.

Cyclodextrins, sugar-based molecules frequently used as safe 'inactive' ingredients (excipients) to improve drug delivery, possess a remarkable property: they bind and transport cholesterol. Preclinical research has sparked excitement, showing cyclodextrins can alleviate AD-like pathology in experimental models, possibly by correcting cholesterol imbalances. This raises a crucial question: could individuals already exposed to cyclodextrins through their everyday medications be inadvertently receiving a protective benefit against AD, especially those carrying the high-risk APOE4 gene?

Answering this question will require us to analyse health data on an impressive scale. This MRes project leverages the unique power of the UK Biobank, a world-leading resource of molecular, clinical and prescribing data for 500,000 participants. The Personalised Medicine Centre is well positioned to conduct a large-scale data-driven human study exploring this specific hypothesis.

This project will equip you with experience of data driven biomedical analysis and introduce you to the UK Biobank, a world leading research resource that is growing in scale and significance and is central to the UK’s biomedical data science programme.

We will tackle a novel question with direct translational potential – could a commonly used compound be repurposed or optimised for AD prevention in genetically vulnerable individuals?  You will gain cutting-edge skills in genetic epidemiology, pharmacology, bioinformatics, and the analysis of large-scale human health data, contributing vital evidence in a critical area of unmet medical need.

Specific skills requirements of the applicant: Programming skills in Python or R.

Important Information: Applications for more than one MRes studentship are welcome, however if you apply for more than one MRes project within Medicine, your first application on the system will be deemed your first-choice preference and further applications will be ordered based on the sequential time of submission. If you are successfully shortlisted, you will be interviewed only on your first-choice application and ranked accordingly. Those ranked highest will be offered a MRes studentship. In the situation where you are ranked highly and your first-choice project is already allocated to someone who was ranked higher than you, you may be offered your 2nd or 3rd choice project depending on the availability of this project.

Essential criteria

Applicants should hold, or expect to obtain, a First or Upper Second Class Honours Degree in a subject relevant to the proposed area of study.

We may also consider applications from those who hold equivalent qualifications, for example, a Lower Second Class Honours Degree plus a Master’s Degree with Distinction.

In exceptional circumstances, the University may consider a portfolio of evidence from applicants who have appropriate professional experience which is equivalent to the learning outcomes of an Honours degree in lieu of academic qualifications.

• Experience using research methods or other approaches relevant to the subject domain
• A comprehensive and articulate personal statement
• A demonstrable interest in the research area associated with the studentship

Desirable Criteria

If the University receives a large number of applicants for the project, the following desirable criteria may be applied to shortlist applicants for interview.

• First Class Honours (1st) Degree
• Use of personal initiative as evidenced by record of work above that normally expected at career stage.
• Applicants will be shortlisted if they have an average of 75% or greater in a first (honours) degree (or a GPA of 8.75/10). For applicants with a first degree average in the range of 70% to 74% (GPA 3.3): If they are undertaking an Masters, then the average of their first degree marks and their Masters marks will be used for shortlisting.
• Relevant professional qualification and/or a Degree in a Health or Health related area

Equal Opportunities

The University is an equal opportunities employer and welcomes applicants from all sections of the community, particularly from those with disabilities.

Appointment will be made on merit.

Funding and eligibility

This opportunity is open to UK/ROI applicants only.

MRes studentships will be available to top ranked candidates to cover tuition fees and a Research Training Support Grant of £900. All applicants will be considered automatically for an MRes studentship. Applicants who do not receive a studentship but meet admission requirements may be offered admission on a self-funded basis.

Applicants who already hold an MRes or a doctoral degree or who have been registered on a programme of research leading to the award of an MRes or doctoral degree are NOT eligible to apply for an award. Applicants who hold or who are registered on a taught Master’s degree are eligible to apply.