$125,000 awarded to Dr. Janice Robertson at the University of Toronto.
ALS disease onset and progression vary significantly from person to person and scientists need to understand why this variation happens in order to effectively diagnosis and treat the disease.
One of the landmark discoveries in understanding ALS was that the most common genetic cause of ALS and frontotemporal dementia is a mutation where the C9orf72 gene has abnormal repetitive pieces of DNA called a repeat expansion. After several years of studying C9orf72 in people with ALS, scientists have learned that abnormalities appear to be different in one area of the brain and spinal cord versus another, but this has been difficult to confirm.
In this pilot project, Dr. Robertson and her Postdoctoral Fellow, Dr. Paul McKeever, will be among the first researchers to apply two powerful new techniques; single-nucleus RNA-sequencing (sNuc-Seq) and assay for transposable-accessible chromatin sequences (ATAC-Seq), towards ALS research. Using archived samples of brain and spine tissue from people who had ALS with a mutated C9orf72 gene, people who had sporadic ALS, and people without ALS, she will perform sNuc-Seq and ATAC-Seq on the tissue in order to better understand the differences in ALS pathology at a single cell level.
Drs. Robertson and McKeever’s work will not only determine if there are differences in single cell level pathology from one brain region to another, but also whether differences can occur within a single region and in different cell types. Their research suggests this deep-dive analysis will confirm that the variations in ALS might be explained by pathological differences from cell-to cell. If correct, Drs. Robertson and McKeever hope to scale up this research to test a much larger number of people in order to revolutionize our understanding of the disease, and our ability to treat it.