Elucidating RNA metabolism changes underlying the progressive neural cell biology of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease. It progresses rapidly, and it is always terminal. It affects 1 in 400 people and has no known cure. 

Disturbance of genetic ‘messages’ of RNA are always seen in ALS, and I aim to understand these changes at region, cell-type and temporal resolution. I will integrate experimental and computational approaches with study of human post-mortem tissue and stem cell models to identify key RNA messages that contribute to the development of the disease. I will also reveal master regulator genes whose altered activity initiates the RNA disturbances and work out how RNA abnormalities in varied cell types, such as nerve or support cells, collectively cause the death of motor neurons. 

My findings will facilitate the design of effective treatments for ALS.