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(MCRC Clinical) Investigating the requirement for MOZ and its HAT activity, in human AMLs


Project Description

Project summary:
Treatments for Acute Myeloid Leukaemia (AML) have not dramatically changed, or improved, for the last 30 years. The current treatments are very debilitating, associated with high morbidity and inappropriate for a large fraction of patients. Therefore, there is pressing need for the development of more specific and efficient therapies. MOZ (MOnocytic leukaemia Zinc-finger protein, also called MYST3 or KAT6A) is a Histone Acetyl Transferase (HAT) of the MYST family of proteins that regulate chromatin conformation through histone acetylation. MOZ was first identified in AML as a recurrent chromosomal translocation t(8;16)(p11;p13) resulting in the fusion of MOZ with CBP. MOZ translocations are associated with a rare subtype of monocytic and myelomonocytic leukaemia which affects mainly young patients and confers a dismal prognosis. Interestingly, MOZ-related and MLL-associated AMLs display a similar gene expression pattern, suggesting that these two very aggressive subtypes of AML share molecular pathways that might drive leukaemogenesis. We have accumulated evidence that MOZ, and its HAT activity, might be specifically required for the growth of murine leukaemic cells. The main aim of this study is to investigate the requirement for MOZ, and its HAT activity, for the maintenance of human leukaemic cell lines and primary leukaemia samples. This project is ideally suited to a haematologist given its main focus on acute myeloid leukaemia.

Entry Requirements:
Candidates must be post-registration clinicians and ideally have a specialist post in a related subject, for example, obstetrics and gynaecology, oncology, or primary care. Applicants must have been resident and worked within the EEA (European Economic Area) for at least three years prior to application.

Funding Notes

The clinical fellowships are usually tenable for three years, although in certain circumstances they may be four years duration. We will provide running expenses, an appropriate salary in line with the applicant’s current salary and grade, and full coverage of University PhD fees. Where international student fees are payable, please provide evidence with your application of how the shortfall will be covered (approximately £19,000 per annum).

The length of this project will be FOUR YEARS.

Related Subjects

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