Project Description

About the Project

Aside from messenger RNA (mRNA), a whole raft of small non-coding RNAs are at work in the cell, but these have been relatively neglected in studies of genetic and epigenetic regulation. The unique metabolism of the prostate makes it difficult to infer regulatory processes from other tissues, and the small number of studies into the regulation of small RNA expression in the prostate have tended to focus on cancer tissue which has its own unique biology.

Uniquely, we have assembled a data set of small-RNA profiles, methylation profiles and germline variants for non-malignant prostate samples from approximately 200 men. The samples represent a variety of ages and include multiple samples from some men, allowing us to study heterogeneity between and within individuals. The focus is likely to be on microRNAs, with other small RNAs, such as snoRNAs and tRNAs, also considered where appropriate.

While small RNA can regulate mRNA expression, any of germline variation, DNA methylation, or mRNA expression could affect small RNA expression. Additionally, germline variation and methylation can also affect mRNA expression, while germline variation and mRNA expression can influence DNA methylation. The project will model the causal network of events resulting in the regulation of small RNA expression in the prostate, to determine whether the detected associations represent direct causality or are mediated by the other factors being examined. Consideration of how methylation patterns evolve around small RNA loci can also feature.

This project will look to establish models for the regulation of small RNAs taking into account methylation patterns, germline variation and mRNA expression, and will generate a catalogue of regulatory features. These will be validated in other, published, data sets. Results will be tested in other tissues, including cancer cells where these provide a natural experiment through perturbation of the inferred causal networks.

Likely arriving with a statistics/mathematics background or a biology background with strong quantitative skills, the student will gain experience in handling large data sets, bioinformatics skills, and using high-performance computing. Advanced statistical and machine learning approaches will be learnt in order to achieve the modelling of regulatory networks. The student will engage with the University of St Andrews GRADSkills training programme, the Scottish Mathematical Sciences Training Centre, and the UK Academy for PhD Training in Statistics. The student will also be required to engage with the biological aspects of the project and will present to and discuss with bio-focussed audiences.

Funding Information

Funding Notes

This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership.

This opportunity is open to UK and International students and provides funding to cover stipend at UKRI standard rate and UK level tuition fees. The University of St Andrews will cover the Home-International fee difference.

Eligibility Requirements

UKRI eligibility guidance: Terms and Conditions: View Website International/EU: View Website

Application Process

How to apply

Application instructions can be found on the EASTBIO website- How to Apply | EastBio Doctoral Training Partnership | Biology

1) Download and complete the Equality, Diversity and Inclusion survey.

2) Download and complete the EASTBIO Application Form.

3) Please complete an application on our online portal: How to apply – Study at St Andrews – University of St Andrews

4) Select the course ‘PhD with internship’

5) Your online application must include the following documents:

• Completed EASTBIO application form
• Academic Qualifications
• English Language Qualification (if applicable)
• 2 References: this must be completed on the EASTBIO Reference Form, also found on the EASTBIO website.

Please download the EASTBIO reference form and send it to your referees. They can either upload it directly to the portal using the automated email they will receive, or they can email it to Rachel at [email protected]

Contact

Queries on the project can be directed to the project supervisor at [email protected]

Queries on the application process can be directed to Rachel Horn at [email protected]

Application enquires: [email protected]