Regulation of Demand-Adapted Myeloid Haematopoiesis in Infection

About the Project

Our immune system depends on the bone marrow to continually produce the right types of white blood cells needed to fight infection. When the body encounters different pathogens, the bone marrow rapidly adjusts which immune cells are produced. For example, bacterial infections often trigger a surge in neutrophils, tuberculosis increases monocytes, and viral infections such as Epstein Barr virus stimulate dendritic cells. This ability to adapt is essential for effective immunity. However, when this process becomes dysregulated it can cause harm. For instance, excessive neutrophil production has been linked to severe disease in COVID-19.

A key regulator of immune cell development is the gene IRF8, which helps control how blood stem cells develop into different types of immune cells. Studies of patients with rare IRF8 mutations show that IRF8 acts like a “dimmer switch” for immune cell production: reduced IRF8 activity leads to excessive neutrophil production and reduced diversity of immune cells. While IRF8’s role in normal blood formation is increasingly understood, its function in adapting immune cell production during infection remains largely unknown.

This PhD project will investigate how IRF8 regulates immune cell production in the bone marrow during infections that drive distinct immune responses: bacterial sepsis, tuberculosis, and Epstein Barr virus infection. The project will analyse paired blood and bone marrow samples from infected patients and compare them with samples from healthy individuals.

First, the project will define how immune cell populations change during infection, identifying which stages of blood cell development are most affected. Next, advanced single-cell genomic technologies will be used to examine how gene activity and DNA accessibility change in individual bone marrow cells during infection. This will reveal how IRF8-controlled regulatory networks are remodelled as the immune system responds to different pathogens. Finally, the project will map where IRF8 binds across the genome and how this relates to active or inactive regulatory regions controlling immune cell development.

Together, these approaches will uncover the molecular mechanisms that allow the bone marrow to adapt immune cell production during infection. The findings may identify biomarkers to help predict which patients are at risk of severe disease and reveal potential therapeutic targets to restore healthy immune cell balance.

The project will provide broad training in cutting-edge single-cell laboratory and computational analysis techniques at the interface of immunology, stem cell biology, and infectious disease research. Applications are welcomed from students of all backgrounds.

Funding

Students who have, or are expecting to attain, at least an upper second-class honours degree (or equivalent) in a relevant subject, are invited to apply. Funding is available for Home (UK) students to cover tuition fees, a tax-free stipend at the UKRI rate (indicative amount in year 1 in 2026-27, £21,805) and research costs, for four years. Applicants normally required to cover International fees will have to cover the difference between the Home and the International tuition fee rates. There is no additional funding available to cover NHS Immigration Health Surcharge (IHS) costs, visa costs, flights etc.

Funding for this studentship is awarded on a competitive basis and is not guaranteed; availability will depend on the outcome of the selection process and subject to final approval by the University.