Mathematical Modelling of Clonal Dynamics and Mutation-Driven Transformation in Human Haematopoiesis

About the Project

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.

Haematopoiesis, the lifelong process by which blood cells are produced from haematopoietic stem cells (HSCs), offers a remarkable example of dynamic equilibrium. In healthy adults, the total number of active HSCs remains approximately constant, despite continual turnover and differentiation into billions of mature blood cells each day. This homeostasis is maintained through a finely tuned balance between self-renewal, differentiation, and cell loss. However, with age, the accumulation of somatic mutations within HSCs leads to the emergence of genetically distinct clones, a phenomenon known as clonal haematopoiesis (CH). While most such clones remain benign, certain mutations confer proliferative advantages and can become precursors to blood cancers such as chronic myeloid leukaemia (CML) or acute myeloid leukaemia (AML).

This project will develop and analyse stochastic mathematical models of HSC population dynamics to understand how mutations alter the balance between self-renewal, proliferation, and differentiation, ultimately driving clonal dominance and disease onset. The project will build on recent breakthroughs in single-cell genomics and phylogenetic reconstruction of HSC lineages (e.g. Mitchell et al., Nature, 2022; Kamizela et al., Nature, 2025), which now allow quantitative inference of cell division rates, mutation accumulation, and clonal fitness over the human lifespan. These data provide, for the first time, a basis for parameterising mechanistic models of human haematopoiesis.

The student will develop a hierarchy of mathematical frameworks, ranging from stochastic birth–death and branching processes to Gillespie simulations and continuum approximations, to capture how individual mutations modify stem-cell behaviour. Particular emphasis will be placed on modelling how mutations that enhance self-renewal or reduce apoptosis perturb the homeostatic equilibrium, and how combinations of mutations can lead to rapid clonal expansion. The models will be used to quantify key emergent properties such as latency to malignant transformation, incidence rates with age, and variability between individuals.

This project is highly interdisciplinary and will suit applicants with a strong quantitative background (mathematics, physics, engineering, computer science, or quantitative biology) who are motivated to apply mathematical thinking to fundamental biomedical questions. The work has potential impact both in basic science: elucidating how normal ageing predisposes to cancer and in translational medicine, by helping to predict when and how pre-leukaemic clones evolve towards overt malignancy.

Informal enquiries can be made by contacting Dr A Moura (a.moura@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 Physics or a relevant subject.

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 titleon 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

Funding Notes

This is a self-funding project open to students worldwide. Our typical start dates for this programme are February or October.

Fees for this programme can be found here Finance and Funding | Study Here | The University of Aberdeen.