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Gene Regulation by the KAT6A/MOZ Histone Acetyltransferase

  • Full or part time
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

The human KAT6A and KAT6B genes encode the nuclear proteins MOZ and MORF, which are key gene regulators in development of blood, brain and other tissues. MOZ and MORF function as lysine acetyltransferases, i.e. they regulate gene expression via histone acetylation. Mutations in KAT6A and KAT6B leading to loss of expression are associated with neurodevelopmental syndromes involving intellectual disability. In addition, some leukemia patients have been found to have fusions of the KAT6A or KAT6B genes to other genes resulting in expression of oncogenic MOZ and MORF fusion proteins. Recent advances in the field have shown targeting the MOZ can halt expansion of leukemic driven by these fusion proteins in preclinical models. Thus, drugs that block MOZ/MORF function may be promising cancer therapeutics, whereas restoring MOZ/MORF function may have benefit for patients with genetic abnormalities in KAT6A/KAT6B

A project is available to characterise novel function domains we have identified in MOZ and MORF proteins that are critical for their function. This will build on our previous studies of the molecular functions of these proteins (e.g. Dreveny et al., NAR 2014). In our current studies we are using CRISPR genome editing to introduce mutations similar to those found in KAT6A patients, to assess the impact on gene expression by RNA Seq. These cell lines enable us to explore MOZ function by rescue with normal or mutated MOZ proteins to explore function (manuscripts in preparation). The project will involve characterisation of novel functional domains using a range of state of the art molecular biology techniques including CRISPR genome editing, BioID, western blots, RTqPCR, chromatin IP analyses, confocal microscopy, protein-protein protein/DNA interaction studies.

The project will be carried out within the Gene Regulation & RNA Biology Group (circa 25 researchers) within the Division of Molecular & Cellular Sciences. The School of Pharmacy provides a vibrant cross-disciplinary research environment, with excellent support and training facilities for PG students.

Funding Notes

Applications are welcome from motivated students with Bachelors (2.1 or above) or Masters degree(s) in Science subjects. Applicants should visit our University pages for information regarding fees and funding at the University. Sponsored and self-funded students are welcome to contact me directly for further information ()

How good is research at University of Nottingham in Allied Health Professions, Dentistry, Nursing and Pharmacy?
Pharmacy

FTE Category A staff submitted: 44.10

Research output data provided by the Research Excellence Framework (REF)

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