Regulated transcription of genes in the cell nucleus is central to all life processes. This is achieved by the coordinated actions of hundreds of DNA-binding transcription factors, chromatin regulators and RNA Polymerase complexes. Our group studies KAT6A and KAT6B which encode two large nuclear proteins that function as histone acetyltransferases, adding acetyl groups to specific lysines within histone H3 and some non-histone proteins. KAT6 genes are expressed in stem cells and are required for development of blood, bone and other tissues. Mutations in KAT6 genes in early development are associated with rare neurodevelopmental disorders, whereas chromosomal rearrangements of the KAT6A locus are implicated in childhood leukaemias and other cancers. Small molecules targeting KAT6A are currently in clinical trials as potential cancer therapeutics.

Our group focuses on understanding the molecular structure and functions of the KAT6 proteins and their interactions with chromatin via a series of N- and C-terminal domains. We use CRISPR editing to study KAT6 functions and the effects of disease mutations in cellular models. Projects are available which offer the opportunity to learn molecular and cellular biology techniques, protein-protein and protein-DNA interactions, confocal microscopy, CRISPR gene editing and structural biology etc. Structural studies are performed in collaboration with Diamond Light Source.

We are interested to hear from strongly motivated candidates with a relevant MSc or BSc degree (or equivalent) who have secured or intend to seek sponsorship or other independent means to cover fees, living and research expenses. Excellent written and oral English language skills are essential. Information on schemes for home / EU and international students is available on the University of Nottingham website.

Projects will be hosted within the Gene Regulation & RNA Biology group, BioDiscovery Institute, under the School of Pharmacy (ranked 12^th in World QS Rankings)

University of Nottingham

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The KAT6 Chromatin Regulators: Understanding Structure & Function