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

Summary

The project is open to UK and ROI applicants only.

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?  We will answer this question by exploring prescribing patterns of cyclodextrin based medicines and incidence of Alzheimer's disease to determine the relationship between the two.

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.

Objectives of the research:

To determine the association between prescribing practices of cyclodextrin based medicines, incidence of Alzheimer's disease and the strength of the associations observed.

Methods to be used:

This study will be entirely data-driven and exploit our existing access to the UK Biobank.  Data analysis in Python or R will be undertaken to explore the statistical relationships between cyclodextrin receiving patients, Alzheimer's patients and patients belong to both groups. Dose response effects will also be explored.

Skills required of the applicant for this project:

Programming skills in Python or R.

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 demonstrating interest in the subject area

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.

• Applicants should hold, or expect to hold a First Class Honours Degree in a relevant subject area
• Relevant professional qualification

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

The project is open to UK and ROI applicants only.

To be eligible for these scholarships, applicants must meet the following criteria:

• Be a UK National, or
• Have settled status, or
• Have pre-settled status, or
• Have indefinite leave to remain or enter, or
• be an Irish National

Applicants should also meet the residency criteria which requires that they have lived in the EEA, Switzerland, the UK or Gibraltar for at least the three years preceding the start date of the research degree programme.

Studentship funding is available as follows:

• MRes studentships will be available to top ranked candidates to cover tuition fees and a Research Training Support Grant of £900.
• All applicants to the project 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 funding.
• Applicants who hold or who are registered on a taught Master’s degree are eligible to apply.