Uncovering the role of the complement system in driving damage to motor neurones by microglia in MND

ALS causes the progressive loss of the neurons that control movement, but we still do not fully understand why these cells die. Increasing evidence suggests that microglia, the brain's resident immune cells, can switch from protecting neurons to driving disease. This project investigates whether the complement system, an important part of the immune response, is responsible for activating harmful microglia in the most common genetic form of ALS caused by C9orf72 hexanucleotide repeat expansions. Using human stem cell-derived models of microglia and motor neurons, we will identify how complement signalling contributes to nerve cell damage and test whether blocking this pathway can protect neurons. The ultimate goal is to identify new therapeutic targets that could slow disease progression and pave the way for future treatments for ALS.