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Structure Function Studies of KAT6A/MOZ, a Key Gene Regulator in Cancers

School of Pharmacy

About the Project

A project is available to study the structure and function of KAT6A (also known as MOZ), a key protein in gene regulation, development and cancer. This protein is a member of MYST of lysine acetyltransferases, and functions in chromatin modification to regulate gene expression. Originally identified as an oncogene, our earlier work focused on the role of MOZ in the development of acute myeloid leukemia (Sheppard et al. MCB 2001; Matsuda et al., JBC 2004; Kindle et al., MCB 2005; Collins et al JBC 2006; Waters et al., et al., JBC 2006; Kindle et al., Leukaemia 2010).

Recently we characterised the structure of a domain in MOZ (the double PHD finger) can bind and acetylate the Histone H3 tail and induce its alpha helical conformation and acetylate H3K9 and H3K14 in chromatin (Dreveny et al., NAR 2014).We have now defined additional functional domains with novel roles in chromatin recognition. The project will involve characterising these novel functions using structural analysis (X-ray crystallography) and mutagenesis. Using cancer cell lines depleted of MOZ by CRISPR CAS9 editing, RNA-Seq was used to establish transcriptomes and thus MOZ-regulated genes (manuscripts in preparation). This project will also involve rescue experiments with wild type and mutant MOZ proteins, to enable us to understand the role of novel MOZ domains in gene regulation and in leukemias.

The project will involve the use of molecular and cell biology techniques, including protein purification and structural analysis, supported by gene expression, chromatin binding studies and confocal microscopy.

The project will be carried out within the Gene Regulation & RNA Biology Group (circa 30 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. International applicants should visit our University pages for information regarding fees and funding at the University. Sponsored and self-funded students are encouraged to contact me for further information

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