Neurodegeneration
Our brains contain immune cells called microglia that normally help keep the brain healthy. In Alzheimer’s disease these cells stop working properly. This project looks at how genetic differences linked to Alzheimer’s change the way microglia control their genes, to better understand what goes wrong in these important cells.
We grow human microglia in the laboratory from stem cells, and compare cells that carry an Alzheimer’s-associated genetic change with otherwise identical healthy cells. Using gene-editing (a technique called CRISPR), we carefully remove individual DNA switches and then measure whether the nearby genes change their activity. This tells us whether each switch is really needed to control its gene.
By linking specific regulatory DNA to gene activity in human microglia, this work will help build a clearer picture of how genetic risk affects microglia in Alzheimer’s disease. Understanding this is a necessary foundation for the longer-term goal of finding better ways to detect, treat and slow the disease.
NIHR Exeter BRC.
Dr Sean Flynn & Dr Tom Piers.
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