Mapping Alternative Polyadenylation and Splicing in ALS via Single-Nucleus Long-Read Transcriptomics

In cells, RNA processing is a crucial mechanism that converts genetic instructions (DNA) into properly formed proteins. When this system is affected, it can contribute to the cellular stress and degeneration seen in diseases like ALS. In this project, Dr. Robertson and team aim to identify disruptions in RNA processing linked to disease, including changes that make brain cells more vulnerable to ALS.

By using an advanced sequencing method to uniquely read RNA molecules from individual motor neurons, the study aims to identify new patterns and markers inside affected cells, creating a high-quality dataset that could support a better, deeper understanding of ALS and inform the development of improved treatments. The study will focus on motor neurons from people living with C9orf72-ALS, those with no known genetic variants, and healthy controls.

Read more about the lab’s previous work here.

In 2006, the landmark discovery that 97% of ALS cases had abnormalities in the biology of a protein called TDP-43, that plays several important roles in how cells manage their RNA, shifted fundamental ALS research significantly. Since this, several researchers have highlighted abnormal RNA biology as a likely critical process underlying motor neuron health in the disease. ALS Canada funding has significantly impacted the field’s continually evolving understanding of these complex systems.