A funded PhD project (4 years) is available to study the structure/function of KAT6A, an important regulator of gene expression in cancer and stem cells. KAT6A encodes a histone acetyltransferase that controls development of blood cells and other tissues. Mutations in this gene are implicated in childhood leukaemia and neurodevelopmental disorders. Our recent work defined the structure of the KAT6A Double PHD Finger (DPF) domain that engages with histone tails to facilitate acetylation (Dreveny et al., Nuc. Acids Res 2014).
This project will characterise a novel DNA binding function we recently identified in this regulator. The project will help understand KAT6A function, the aetiology of KAT6A-related disease and facilitate translational research towards therapeutics/disease management.
This multidisciplinary project will be split between the Diamond MX Group/Research Complex at Harwell and the Gene Regulation Group, School of Pharmacy at the University of Nottingham. The candidate will spend time at both institutions and benefit from having access to world-leading facilities at Diamond/RCaH for protein structure determination and biophysical analysis of protein/DNA complexes. The molecular function studies will be performed at the School of Pharmacy, Nottingham, (ranked 5th in QS World Rankings, 2021 for Pharmacy /Pharmacology). The School of Pharmacy offers an excellent multidisciplinary research environment with >180 PhD students and 60 Post-doctoral researchers and has an exemplary completion record for PhD students. The Rutherford Appleton site with its world leading facilities, including Diamond, ISIS and CLF offers a multidisciplinary environment complemented by the newly established Rosalind Franklin Institute. Diamond comprises a suite of seven MX beamlines, a dedicated bioSAXS beamline, the XFEL hub, the electron Bio-Imaging Centre (eBIC) and the Membrane Protein Laboratory (MPL). Together with the adjacent Research Complex at Harwell which houses a range of life and physical science activities, including both CCP4 and state of the art structural biology laboratories these are providing exceptional opportunities for synergies and collaborations. We will provide a full and inclusive training package for the PhD student and are proud of our inclusive culture that celebrates diversity and strongly promotes research integrity.
Candidate Requirements:
Candidates should have an interest in learning skills in structural biology and analytical techniques (X-ray crystallography, bioSAXS, cryoEM) as well as training in molecular and cell biology techniques (protein expression/purification, protein DNA interaction studies, site-directed mutagenesis, RTqPCR expression analysis, CRISPR CAS9 editing, chromatin IP, confocal microscopy). A first degree in a relevant science subject, normally equivalent to UK 2:1 level, and/or a relevant postgraduate Master's qualification. Excellent oral and written communication skills are required, in addition to high motivation and adaptability, and the ability to work both independently and within a team. Experience in molecular biology, biochemistry techniques or structural studies is desirable.
How to apply
Formal applications must be submitted through the University of Nottingham online application form - https://www.nottingham.ac.uk/pgstudy/how-to-apply/research.aspx. Please choose “Pharmacy PhD” as course and mention “KAT6A structure” and “Prof. David Heery” as contact person. Applications should include a Curriculum Vitae, contact information for two potential referees and a short summary of research experience and expression of interest.
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