Investigating the role of lysine methylation in the DNA damage response.

Our genomic DNA is under constant attack from DNA damaging agents, which are a continuing threat to genomic integrity. Defective resolution of DNA damage underlies several human diseases, including neurological abnormalities and developmental disorders as well as cancer. To counteract this, multiple DNA damage response (DDR) proteins act to combat DNA damage, by detecting DNA damage, activating cell cycle checkpoints, and promoting the repair/resolution of DNA lesions. The activity of these factors is controlled by a complex network of post-translational modifications.

My group is interested in one particular post-translational modification, lysine methylation, and the enzymes that catalyse this. These ‘lysine methyltransferases’ play vital roles in maintaining human health and development, and in preventing tumourigenesis. Our main focus in the Higgs lab is on how these enzymes control the DDR and therefore prevent genome instability.
This PhD will investigate how the KMT2 family of Lys methyltransferases function in the DDR. The project will involve a wide variety of laboratory techniques, including mass spectrometry, co-immunoprecipitation, RNAi techniques, in vitro activity and binding assays, fluorescent and visual microscopy, immunoblotting and immunofluorescence, molecular cloning, cell culture and CRISPR-based mutagenesis. These approaches will lead to a greater understanding of how lysine methylation is involved in maintaining genome stability and preventing human disease.

For further information, please contact [Email Address Removed].

Person Specification:

Applicants should have a strong background in molecular and cellular biology, with experience of one or more of the following laboratory techniques: mammalian tissue culture; immunofluorescence; immunoblotting or molecular cloning. Previous experience of a research lab environment is essential. They should be ambitious, enthusiastic and self-motivated, and hold at least an Upper Second Class Honours Degree in a relevant biological subject. If applicable, they should also be able to demonstrate proficiency in the English language.