My research programme identifies new genes for inherited disorders affecting the human brain. We also study how these genes function using cells and model organisms. Aicardi-Goutières syndrome is a genetic condition in which faults in genes encoding enzymes called nucleases, mimic viral infection of the brain. These nucleases may normally clean up naturally produced ‘waste’ DNA and RNA, with failure of this process leading to the body mounting an immune reaction against itself. This immune response mechanism is relevant to common autoimmune diseases such as lupus and so we are studying these enzymes to understand their normal roles in cells and to establish what happens when these enzymes fail.
Secondly, we are identifying genes that cause extreme growth failure of the brain and body. Individuals with primordial dwarfism are often described as the 'smallest people in the world'. These genes are components of the core cell machinery which controls cell duplication and mutations likely result in fewer cells being made, leading to a smaller person. Identifying these genes will help diagnosis and management of these rare conditions. It may also help us better understand how the body regulates growth, perhaps shedding light into why humans are bigger than mice and how our brains evolved to be so large.