T Cell Responses in Acute Myeloid Leukaemia

This 4-year PhD studentship will be based at the Cancer Research UK Manchester Institute, New Paterson Building, Withington, Manchester, UK

Recent advances in cancer immunotherapy have yet to benefit patients with Acute Myeloid Leukaemia (AML), despite allogeneic stem cell transplantation demonstrating the curative potential of leukaemia-reactive T cells. Whilst there is evidence that autologous T-cell responses occur in patients with AML, we do not know whether these are common or robust enough to allow therapeutic manipulation. Overall, the immunology of AML remains understudied and poorly understood. Contributing factors include the complexity of bone marrow, where large numbers of developing, circulating and resting T cells complicate identification of those relevant to disease pathogenesis. Additionally, contemporary approaches such as single-cell sequencing are expensive and generally not powered to identify rare populations that may constitute <1% of T cells.

To address this problem, we developed a T-cell focused mass cytometry panel and analysed ~400m cells from the bone marrow of 160 AML patients, identifying novel T-cell populations associated with AML genotype and clinical outcome. The focus of this PhD project will be the isolation and characterisation of these leukaemia-associated populations. This will involve isolation of rare populations using fresh patient samples, the application of T-cell receptor sequencing to determine clonality, co-culture with autologous leukaemia to establish reactivity and cytotoxic potential, and the use of tissue sections to study localisation and physical association with leukaemia. These results will inform therapeutic strategies to promote anti-tumour immune responses.

This project would enable the successful candidate to work in the world-leading research environment of the CRUK Manchester Institute, whilst applying cutting-edge techniques to address a critical clinical problem. Students would gain broad exposure to immunology, haematology, oncology and transplantation. Upon completion, candidates would be well positioned to pursue a career in the fascinating and expanding field of cellular immunotherapy for cancer.

We are looking for a hard-working, focused, ambitious person to join our excellent, friendly and interactive team. Our laboratory makes use of a broad range of in vitro and in vivo techniques to study interactions between leukaemia and immune cells, with the aim of developing novel therapies for patients. Our approach spans cutting-edge single cell sequencing and epigenetics, through to murine models, biomarker development and clinical trials.

We would be particularly happy to receive applications from individuals with a strong academic track record and Masters-level and/or other laboratory research experience in leukaemia, cancer biology or immunology. Applicants should hold or expected to graduate with a first or minimum upper-second class undergraduate honours degree (or equivalent from a non-UK university) as part of a university degree course.   

The Cancer Research UK Manchester Institute is proud to be a diverse, open, and global Institute. Our priority, and that of the University of Manchester, is to support our current students and welcome new ones from Europe and other continents, we therefore encourage students of all nationalities to apply for the programme.

Applicants can find full group details, and information on how to apply via the CRUK Manchester Institute’s online PhD recruitment portal: https://www.cruk.manchester.ac.uk/Education/PhD-2024-Apply

Group Leader: Mark Williams

Research Group: Leukaemia Immunology & Transplantation

Application Deadline: Friday 17 May 2024 – 1700 hrs (GMT)

Interview date: Monday 17 June 2024, new Paterson Building, Manchester, UK

We plan to hold in-person interviews however, we will take into consideration any change in circumstances at the time to ensure the safety of all concerned and we may amend the interview format to virtual if deemed necessary.