JAMT: Somatic mutations as drivers of ageing and chemotherapy-induced immunosenescence

About the Project

This PhD will reveal the consequences of ageing-acquired and chemotherapy-induced somatic mutations for T cell function and immune regulatory pathways in health and disease.

Background

Older age is a major risk factor for cancers, autoimmune disease, and mortality following infections. Consequently, older people require more care, significantly adding to rising healthcare costs worldwide. As we get older our immune system ceases to function as efficiently compared to when we were younger, and for cancer patients’, chemotherapy can significantly impact immune function. Therefore, finding ways to monitor and promote healthy immune ageing will improve quality of life for cancer patients and older people, and reduce pressure on healthcare systems.

Key to the pathology of the above diseases are T lymphocytes of the adaptive immune system, either via killing malignant or pathogen-infected cells, secreting paracrine signalling proteins like cytokines, or by dysregulated activation in the case of autoimmunity. Memory T cells are long lived, required for vaccine immunity, and go through multiple rounds of cell division during the clonal expansion of an immune response, and homeostatically to maintain durable immune memory against pathogens.

Somatic mutations are individually rare but accumulate at a steady rate in the DNA of T cells as a person ages. Memory T lymphocytes that provide durable immunity, accumulate more mutations than naïve T cells [1]. In tandem, cytotoxic chemotherapy has been shown to induce extensive somatic mutations in haematopoietic cells [2,3], suggesting T cells of cancer patients are significantly compromised, weakening their ability to fight cancer and infections, and form effective immune memory after vaccination. New data from the Morgan lab suggests T cell somatic mutations burden affects T cell regulation pathways, including mitochondrial function, cytokine signalling and proteostasis. However, in both healthy older people and cancer patients, the impact of mutations on T cell function, immune ageing and cancer outcomes, has not been investigated.

While T cell function may be compromised in some cancer patients, the composition of T cell phenotypes varies across patients with different haematological malignancies. In multiple myeloma, there is skew towards clonally expanded effector CD8+ killer T cells, which correlate with response to bispecific T cell engager therapy [4], but which express markers of exhaustion, e.g. PD-1, TOX [5]. However, compared to B cell lymphoma, myeloma patients show relatively low levels of functionally exhausted T cells [6]. To understand the relative consequences of chemotherapy and somatic mutations for T cells from patients with different blood cancers we therefore need to know what the composition of T cell functional states is in these patients.

Training Offered

This interdisciplinary PhD blends experimentation and computation to deliver patient benefit. The project will provide strong interdisciplinary training in cutting-edge immunology, bioinformatics, microscopy and genomics across the Morgan and Sutherland labs, supported by clinician Dr Gavin Preston. Blending experimentation and computation in the Morgan lab, the trainee will identify somatic mutation drivers of T cell immunosenescence using single-cell RNA-sequencing gaining deep computational biology training. Flow cytometry assay optimisation will develop the student’s experimental immunology skillset guided by the supervisors Preston & Sutherland, while live cell imaging coupled to whole genome sequencing will quantify defects in T cell activation kinetics caused by chemotherapy and somatic mutations. Collectively, these experiments will equip the trainee with all the necessary skills required to embark on a scientific career at the cutting-edge of biomedical research. Moreover, as a joint member of the Morgan and Sutherland labs, with co-supervision from clinician Dr Gavin Preston, the student will interact with biologists, clinicians, bioinformaticians and statisticians, thus providing opportunities for them to broaden their interdisciplinary skillset.

Informal enquiries are encouraged, please contact Dr Mike Morgan (michael.morgan@abdn.ac.uk) for further information.

Candidate Background:

The ideal candidate will be curious, highly motivated, with excellent critical analysis, organisational and communication skills and a strong desire to integrate experimentation and computation to solve challenging biomedical problems. Candidates should have a first-class degree or 2:1 (or equivalent) in a subject related to immunology, cell biology, genomics, genetics, biomedical sciences or a quantitative biomedical subject, e.g. bioinformatics. Previous research lab experience is advantageous, particularly in a genomics or immunology setting involving primary cell culture. Experience with data science and programming is desirable given the interdisciplinary nature of the project; however, training will be given for candidates with no prior programming or statistics experience.

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 Mike Morgan - [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. The project is expected to start in October 2026.