Investigating the recovery of blood stem cells from infection

Primary Supervisor - Professor Stuart Rushworth 

The ability of haematopoietic stem cells (HSC) to expand and differentiate is key to normal homeostasis and the systemic immune response. HSCs promote a rapid immune response by generating innate and adaptive immune cells that are recruited to the site of infection. After the infection has been overcome HSC numbers decline to pre-infection levels, however what controls this reduction in numbers is not known.  Our laboratory has shown that the non-haematopoietic cells (fibroblasts and adipocytes) support HSC maintenance in the bone marrow (BM) microenvironment. Others have shown that BM macrophages also support HSC expansion. However, the primary function of macrophages is phagocytosis (to engulf dead cells, debris or microbes).  Recently, a pathway called cGAS-STING, which is activated by DNA has been shown to be important in clearing dead cells. Here we hypothesise that cGAS-STING pathway controls the reduction of HSC and progenitor cells in the BM after infection and that deficiencies in cGAS-STING allow for a dysfunctional HSC phenotype. Therefore, we aim to study the role of macrophage cGAS-STING pathway on regulating the HSC pool in the BM microenvironment in response to infection and whether defective cGAS-STING leads to a dysfunctional immune response. The PhD student will be trained in vivo techniques including animal handling, isolation of primary cells and techniques to assess functional characteristics of cells including FACS analysis, qPCR to analyse nucleic acids and western blot, ELISA and immunohistochemistry for protein analysis. This will give them a number of valuable transferrable skills which will help their scientific career progression. The project will be carried out at the Rushworth Lab based at the Norwich Medical School, UEA, which combines research laboratories with medical training facilities. This work will be in close collaboration with the Beraza Lab at Quadram Institute, Norwich Research Park. 

The Norwich Research Park Biosciences Doctoral Training Programme (NRPDTP) is offering fully funded studentships for October 2025 entry. The programme offers postgraduates the opportunity to undertake a 4-year PhD research project whilst enhancing professional development and research skills through a comprehensive training programme. You will join a vibrant community of world-leading researchers. All NRPDTP CASE students undertake a three to 18-month placement with the non-academic partner during their study. The placement offers experience designed to enhance professional development. Full support and advice will be provided by our Professional Internship team. Students with, or expecting to attain, at least an upper second-class honours degree, or equivalent, are invited to apply. 

This project has been shortlisted for funding by the NRPDTP. Shortlisted applicants will be interviewed on 28, 29 or 30 January 2025.  

Visit our website for further information on eligibility and how to apply: https://biodtp.norwichresearchpark.ac.uk/ 

Our partners value diverse and inclusive work environments that are positive and supportive. Students are selected for admission without regard to gender, marital or civil partnership status, disability, race, nationality, ethnic origin, religion or belief, sexual orientation, age or social background. 

Additional Funding Information

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 (2024/5 stipend rate: £19,237), and a Research Training Support Grant of £5,000pa for each year of the studentship. 

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