Human developmental disorders of chromatin remodelling

A number of rare genetic human disorders caused by mutations in genes that encode various components of chromatin remodelling machinery are now known. Taken together, these diseases form a substantial health-care burden, especially in the paediatric population. We use deep-phenotyping, family-based studies and next generation sequencing to discover novel human developmental disorders that are caused by defective chromatin remodelling and related processes.

We use these discoveries to understand the biological roles of the involved genes in the context of human disease through a variety of cellular and animal models. Ultimately our goal is to understand the fundamental biology of chromatin remodelling and translate this knowledge to improve clinical care and treatments for patients.

Principal investigator: Dr Siddhart Banka

Epigenetic regulation in aggressive cancers

We are interested in understanding the role of enhancer-associated plasticity in driving the progression of aggressive cancers (breast, pancreatic and oesophageal) which are in unmet need to target. We particularly investigate how chromatin remodelling complexes and noncoding enhancer-derived transcripts exhibit disease-specific reprogramming of gene expression which leads to drug resistance and metastasis, using genome-wide CRISPR knockout screens and combinatorial analyses of ChIP-seq, ATAC-seq and RNA-seq.

Principal investigator: Dr Sankari Nagarajan

Histone modifications and stress signalling

Epigenetics are the heritable changes in gene expression independent of DNA. Alterations in the epigenome can promote the development of age-associated diseases such as neurodegeneration, diabetes, and cancers. Our research focuses on methylation at H3K4, a heritable histone modification potentially controlling age-associated stress signalling pathways.

Principal investigator: Dr Gino Poulin

The mechanisms of signal-dependent transcriptional control

We are investigating how extracellular signals give rise to distinct gene expression programmes and resulting cell fate changes in embryonic stem cells and cancer cells. In this context we also study the underlying changes in the regulatory chromatin architecture that accompany the changes in transcriptional dynamics.

Principal investigator: Professor Andy Sharrocks