JAMT: Systems level analysis of androgen receptor signalling and supraphysiological testosterone therapy in prostate cancer

About the Project

Prostate cancer is driven by signalling through the androgen receptor (AR), and advanced disease is treated by suppressing testosterone production and action. Although initially effective, this approach almost always fails as tumours adapt and become therapy‑resistant. Paradoxically, recent clinical trials show that supraphysiological testosterone, delivered as Bipolar Androgen Therapy (BAT), can suppress tumour growth and re‑sensitise cancers to standard hormone therapies in a subset of patients.

The biological basis of this response remains poorly understood.

This project will investigate how different testosterone concentrations reprogramme AR signalling, and how these changes relate to clinical response to BAT. Building on preliminary RNA‑seq data, the project will test the hypothesis that AR signalling is non‑linear and context‑dependent.

Objectives:

1. Define transcriptional programmes activated at low, physiological, and supraphysiological androgen levels using RNA‑seq and systems analysis of biological pathways and gene networks.
2. Identify molecular signatures (AR output, DNA damage response, cell‑cycle stress) associated with supraphysiological androgen exposure.
3. Map these molecular data onto emerging BAT response biomarkers from clinical trials, including baseline testosterone, AR activity, and therapy re‑sensitisation.

Our overall aim will be to develop integrative models linking androgen dose, AR transcriptional state, and therapeutic outcome.

The project will combine RNA‑seq analysis, bioinformatics, pathway modelling, and translational interpretation, with opportunities to integrate mathematical approaches to understand AR signalling in this context.

This work aims to provide a mechanistic framework for patient stratification and biomarker development in testosterone‑based therapies. By linking molecular biology to clinical outcomes, the project addresses an important unmet need in prostate cancer treatment and offers strong training at the interface of cancer biology, data science, and translational research.

Informal enquiries are encouraged, please contact Professor Iain McEwan (iain.mcewan@abdn.ac.uk) for further information.

Candidate Background:

The successful candidate should have a first/2i class honour degree in a relevant biomedical discipline, for example biochemistry, molecular biology, pharmacology or biomedical sciences. A masters in a relevant discipline, including bioinformatics, would be an advantage.

We actively encourage applications from diverse career paths and backgrounds and across all sections of the community, regardless of age, disability, ethnicity, gender, gender expression, sexual orientation and transgender status, amongst other protected characteristics.

Application Procedure

Important note: This project is open only to applicants eligible for the Home/UK fee rate. This includes EU students who hold settled or pre-settled status and meet the relevant residency criteria.

To apply, please submit the following documents via email to smmsn-pgrenquiries@abdn.ac.uk

• A cover letter addressed to the supervisor of the project you're applying for.
• An up-to-date CV detailing your academic qualifications, employment history, and any other relevant experience. Please ensure your current permanent address is clearly stated, as this will be used to determine your fee status.
• Clear copies of your degree certificates and transcripts (if available).
• Evidence of settled or pre-settled status (if applicable).

Please send your application with documents attached as a single email with the subject line: "JAMT Iain McEwan - [Your Name]"

The deadline for applications is 23:59 GMT on 14th June 2026. Please note that incomplete applications will not be considered.

For any enquiries regarding your application or the application process, please contact smmsn-pgrenquiries@abdn.ac.uk

Funding Notes

This competitively funded research project is one of six opportunities currently advertised by the University of Aberdeen, seeking exceptional candidates. The James Alexander Mearns Trust (JAMT) will fund the project that attracts the most promising applicant.

The fully funded position includes UK/Home tuition fees, research costs, and a tax-free doctoral stipend of £21,805 for the 2026/2027 academic year (increases annually). The project is expected to start in October 2026.