Project Description

As people age, some blood stem cells acquire mutations that give them a growth advantage over their normal counterparts. Our recent work suggests the mutant cells don't just outgrow their neighbours, they actively reshape the bone marrow around them. This change causes a functional change in the normal blood stem cells skewing their production of the immune cells. This project aims to understand which cells of the blood system are affected and what is happening to the cells at the gene and metabolic level with the overarching aim of understanding if this causes accelerated ageing of the normal blood cells.

The successful candidate will build a broad and transferable skillset: designing flow cytometry experiments across the full blood hierarchy, tissue culture, in-vivo modelling, gene expression profiles by RNA-sequencing, and metabolic assays. They will be fully integrated into a collaborative, well-supported research group spanning stem cell biology and metabolism, with regular lab meetings, journal clubs and opportunities to present their work across the Norwich Research Park and at national and international meetings.

This is a highly interdisciplinary project, ideal for someone with a background in molecular or cell biology, immunology, genetics or a related bioscience discipline, and an interest in stem cell biology or ageing. You will be based in the Mistry and Rushworth Lab at Norwich Medical School, UEA, working alongside expert collaborators at the Earlham Institute and across the Norwich Research Park.

Entry Requirements

At least UK equivalence Bachelors (Honours) 2:1. English Language requirement (Faculty of Science equivalent: IELTS 6.5 overall, 6 in each category).

Funding

This project is awarded with a 4-year Norwich Research Park Biosciences Doctoral Training Partnership PhD DTP studentship. The studentship includes payment of tuition fees (directly to the University), a stipend to cover living expenses (2026/27 stipend rate: £21,805, and a Research Training Support Grant of £5,000pa for each year of the studentship.

References

"1. Mistry, JJ, et al. (2026) ‘Stromal cell senescence augments haematopoietic cell fitness in clonal haematopoiesis’, Nature Cell Biology Aug;28(8):1656-1670. doi: 10.1038/s41556-026-02025-

2. Young, K.A. et al. (2025) ‘Elevated mitochondrial membrane potential is a therapeutic vulnerability in Dnmt3a-mutant clonal hematopoiesis’, Nature Communications, 16(1). doi:10.1038/s41467-025-57238-2. 3. SanMiguel, J.M. et al. (2022) ‘Distinct tumor necrosis factor alpha receptors dictate stem cell fitness versus lineage output in dnmt3a-mutant clonal hematopoiesis’, Cancer Discovery, 12(12), pp. 2763–2773. doi:10.1158/2159-8290.cd-22-0086. "

A Hostile Niche: How Mutant Blood Stem Cells Damage Their Healthy Neighbours (MISTRY_U27DTP)

Welcome to Norwich

Project Description

Entry Requirements

Funding

References