Modelling the Self-Regulatory Feedback of the Androgen Receptor under Testosterone Influence

Details

These projects are open to students worldwide, but have no funding attached. Therefore, the successful applicant will be expected to fund tuition fees at the relevant level (home or international) and any applicable additional research costs. Please consider this before applying.

Sex steroids, including androgens, play a central role in regulating cellular function, metabolism, reproduction and cancer. The androgen testosterone acts through the androgen receptor (AR), which is a ligand-activated transcription factor that controls gene expression in a tissue-specific way. Although the effects of AR activation downstream are well studied, the mechanisms controlling AR expression itself, particularly its self-regulation and feedback in response to changing hormone levels, remain poorly understood. These mechanisms are likely to be crucial for maintaining muscle and bone integrity, as well as cardiovascular health, during ageing when testosterone levels naturally decline.

Research aim

This project aims to develop and validate mathematical models that describe the self-regulatory feedback of the androgen receptor under varying testosterone concentrations. Specifically, we will model how fluctuations in hormone levels influence receptor expression, imerization, DNA binding and downstream gene regulation in different cell types.

Methodology

The student will construct and analyse ordinary differential equation (ODE) models of AR-mediated signalling, integrating biological data from laboratory studies in prostate cells. Model parameters will be calibrated using experimental measurements, and model predictions will be compared with observed gene expression patterns. The project will also explore extensions such as stochastic models of single-cell responses and network models of AR-regulated genes.

Training and environment

The project provides comprehensive, interdisciplinary training at the intersection of mathematical biology and molecular endocrinology. Students will gain expertise in:

– mathematical modelling of gene regulatory networks;

– construction and numerical solution of ordinary differential equation (ODE) systems;

– analysis of dynamical systems and sensitivity;

– interpretation of experimental data and model validation.

The work will be carried out in close collaboration with experimental biologists, providing an excellent opportunity to connect theoretical modelling with real-world biological insights. The project also allows flexibility for students to pursue specific research interests.

Impact

Improving our quantitative understanding of androgen receptor feedback control could inform therapeutic strategies for conditions related to hormonal ageing and androgen signalling, such as sarcopenia, osteoporosis and prostate disease.

Informal enquiries can be made by contacting Dr E Ullner (e.ullner@abdn.ac.uk).

Decisions will be based on academic merit. The successful applicant should have, or expect to obtain, a UK Honours Degree at 2.1 (or equivalent) in in a relevant discipline.

This is an interdisciplinary project, and full training will be provided across the different areas involved. Candidates are expected to have prior knowledge or strong aptitude in one or more of the following fields, together with enthusiasm to learn the others:

· Theoretical biology or bioinformatics

· Physics or applied mathematics

· Numerical methods for solving differential equations

· Programming (e.g. C, MATLAB, Python, or Mathematica)

· Parameter fitting and data analysis

· Dynamical systems theory and complex networks

A good command of written and spoken English is essential.

We encourage applications from all backgrounds and communities, and are committed to having a diverse, inclusive team.

Application Procedure:

Formal applications can be completed online: https://www.abdn.ac.uk/pgap/login.php.

You should apply for Degree of Doctor of Philosophy in Physics to ensure your application is passed to the correct team for processing.

Please clearly note the name of the lead supervisor and project title on the application form. If you do not include these details, it may not be considered for the project.

Your application must include: A personal statement, an up-to-date copy of your academic CV, and clear copies of your educational certificates and transcripts.

Please note: you do not need to provide a research proposal with this application.

If you require any additional assistance in submitting your application or have any queries about the application process, please don’t hesitate to contact us at researchadmissions@abdn.ac.uk