Beyond H3K4 Methylation: Mechanistic Insights into How KMT2D Controls Transcription, DNA Repair and Genome Stability Aston University in United Kingdom

This PhD project at Aston University investigates the mechanistic roles of KMT2D, a gene frequently mutated in human cancers and implicated in Kabuki syndrome. The research aims to unravel how KMT2D protects cells from malignant transformation, focusing on its functions beyond H3K4 methylation. Previous studies have shown that loss of KMT2D leads to transcriptional stress, DNA damage, and genome instability, raising questions about which tumour-suppressor functions depend on its catalytic activity and which are non-catalytic.

Using genetic models such as KMT2D-null human cancer cell lines and ΔSET mutants, the project will dissect how KMT2D regulates transcriptional networks, chromatin architecture, replication-stress responses, and DNA repair pathway choice. The research will also assess how loss of full-length or catalytic KMT2D affects cellular responses to DNA-damaging chemotherapy, ionising radiation, and metabolic inhibitors. Methodologies include RNA-seq, ChIP-seq, CRISPR, qPCR, chromatin and protein assays, immunofluorescence microscopy, DNA damage/repair, and genome instability assays. Integrative computational analysis of multi-omic datasets will be central to hypothesis generation and mechanistic interpretation.

The project is co-supervised by Dr TK Kantidakis (transcriptional regulation) and Dr BK Kysela (DNA damage biology), offering rigorous training in cancer epigenetics, chromatin biology, and genome-stability research. The research is directly relevant to precision oncology and developmental disorders, providing a strong foundation for future academic or industry careers.

Funding covers Home tuition fees; overseas applicants must pay the difference between Home and Overseas tuition fees (£17,712 for 2026/7). Associated consumables costs should be discussed with the supervisor before applying. The position is based at Aston Campus in Birmingham, UK, and regular in-person attendance is expected.

Applicants should have a First or Upper Second Class undergraduate degree in a relevant subject, or a First or Upper Second Class undergraduate degree and a Merit or Distinction in a relevant Masters degree. Overseas qualifications will be considered if equivalent. Required documents include transcripts, research and personal statements, CV, two academic references, evidence of English language proficiency, and a copy of passport. Applications must be complete to be considered. Interviews will be conducted online via Microsoft Teams.

For further information, contact Dr TK Kantidakis at [email protected] or the Postgraduate Admissions team at [email protected]. Apply online via the provided link, selecting 'Research - Health Sciences' on the application form.