(MCRC Non-Clinical) Molecular déjà vu: understanding RNA and DNA biology for precision therapy in AML

About the project

About the Project Acute Myeloid Leukaemia (AML) is the most common form of leukaemia in adults with over 3,000 new diagnoses per year in the UK. Currently the management of AML relies heavily on antimetabolite chemotherapies. These compounds are structurally similar to the normal cellular metabolites cells use to make RNA and DNA. Antimetabolites were rationally designed in the mid-20th century based on observations that tumour cells require high levels of the metabolites used to build RNA and DNA. Thus, antimetabolites work by being incorporated into RNA or DNA, leading to dysregulation and cell death. Within this broad mechanism of action lies still unknown molecular details that determine cell responses to antimetabolite chemotherapy. Unlocking these details will generate RNA- or DNA-centred drug targets with defined disease positioning against AML. AML has heterogenous genetic causes. However, there is a convergence of mutations in genes whose protein products impact either RNA or DNA biology. This knowledge and recent functional genomics and molecular analyses have all fuelled studies into RNA as a target for new therapeutics against AML. This molecular déjà vu, rediscovering RNA and DNA to be targetable in AML, has led to successful clinical trials targeting RNA modifications. Targeting RNA should lead to fewer long-term effects from DNA targeting agents, which are known to be mutagenic. There is a need to precisely understand RNA and DNA biology in AML to power precision medicine and position RNA therapeutics to treat specific subtypes of the disease. This studentship aims to define the RNA and DNA changes associated with specific mutations in AML. We will also define and then learn from the precise molecular targets of the antimetabolite therapies administered to AML patients. The student will discover new knowledge while developing experimental skills and expertise in both cancer and nucleic acid biology. Eligibility You must hold, or about to obtain, a minimum Upper Second Class UK honours degree, or the equivalent qualifications gained outside the UK, in a relevant discipline. A related master’s degree would be an advantage International applicants (including EU nationals) must ensure they meet the academic eligibility criteria (including English language) before contacting potential supervisors to express an interest in their project. Eligibility information can be found on the University's Country Specific information page. Before you Apply Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application. How to Apply Apply directly via this link: https://tinyurl.com/577zjazd or on the online application portal, select MCRC PhD Programme as the programme of study. You may only apply for one project within this scheme. Please ensure that your application includes all required supporting documents: Curriculum Vitae (CV) Supporting Statement Academic Certificates and Transcripts Incomplete or late applications will not be considered. Further details are available on our website: CRUK Manchester Centre PhD Training Scheme | Biology, Medicine and Health | University of Manchester Application Timeline Applications open: Monday, 5 October 2026 Application deadline: Monday, 23 November 2026 Interview date: Week commencing 11 January 2027 Start date: September 2027 Equality, diversity and inclusion are central to the University’s activities. The full statement can be found here: https://www.bmh.manchester.ac.uk/study/research/getting-started/equality-diversity-inclusion/

Research areas