Identifying and verifying non-coding genetic causes of amyotrophic lateral sclerosis    

Amyotrophic lateral sclerosis (ALS or motor neuron disease) is untreatable and common. It is largely genetically determined, with 61% of the risk being genetic and 10% of patients with the disease having a family history of it. I aim to discover the basis of this genetic causation.

The majority of DNA does not encode proteins and ‘non-coding’ regions regulate expression of protein-coding regions. Missing genetic causes of ALS are predominantly non-coding, and out of reach of current methods. I have developed pioneering methodology to pinpoint ALS-associated genetic variation in non-coding DNA. I have detected significant novel ALS association in non-coding DNA, including regions controlling expression of the METTL8 gene. I plan to improve my methodology by integrating motor neuron-specific DNA structure. I will validate my discoveries using cell models and develop a genetic test to provide diagnostic and prognostic information to people with ALS.

This research could lead to better diagnosis of ALS as well as new treatments.