“We investigate how cells know who they are”

Around 200 types of cells make up the human body, each with its own unique shape and function. To code for the correct cell type, individual cells need to decide which genes they should switch ‘on’ or ‘off’ during development. Importantly, each cell must ‘remember’ this decision every time it divides. The process and maintenance of switching genes ‘on’ and ‘off’ is central to the biology of a multicellular organism and is influenced by epigenetic mechanisms. 

The Epigenetic Mechanisms and Disease research group aims to understand the regulators, also known as epigenetic mechanisms, that influence which genes will be switched ‘on’ and ‘off’ and how this is maintained. Their studies on the differences between the sexes is regulated at an epigenetic level with a key epigenetic regulator being key – this finding is likely to be important for understanding sex-bias in diseases, for example susceptibility to severe COVID and other infections  as well as autoimmune diseases such as Rheumatoid Arthritis, SLE and MS (Wijchers et al., 2010).  

This group is led by Professor Richard Festenstein, a Clinical Professor of Molecular Medicine specialising in neurogenetics. His work on gene-switching led to the discovery that repeating units of DNA that occur in neurological diseases can switch ‘off’ genes leading to specific diseases. Richard has done a large amount of work on the neurological disease Friedreich’s ataxia (FA), a disease also caused by these repeating units of DNA. Friedreich’s ataxia is a progressive neurological disease causing a decline in balance and coordination as well as causing heart disease. Professor Festenstein showed that the FA gene known as Frataxin is switched ‘off’ by an epigenetic mechanism and can be switched on again by an epigenetic modifier 

This research, contrary to previous beliefs, showed that heterochromatin dynamically allows DNA to be accessed (Science, 2003).

FA is a rare disease affecting 1/50 000 in the UK, making it difficult to develop treatments as a large number of patients are needed for each clinical trial. Richard’s research alongside Professor Faisal’s team devised a novel way of monitoring the effectiveness of treatments for this disease (Nature Medicine, 2023) using motion-capture technology combined with AI and machine learning. Their research continued with colleagues at UCL and UCLH to show that this technology also works in Duchenne Muscular Dystrophy (Nature Medicine, 2023).  The findings of this research promise to make drug development for rare movement diseases more cheaply and quickly.

BBC 5 Live Interview with Professor Richard Festenstein and Yantia, a person with FA.

Explore the future of healthcare in our BBC Breakfast interview featuring a breakthrough AI technology. This AI analyses human movement more accurately and quickly than traditional methods, promising faster, cost-effective drug development. Watch to see how it’s transforming medical diagnostics.