$125,000 awarded to Dr. Valerie Sim, University of Alberta, in collaboration with Dr. Sumit Das, University of Alberta, and Dr. Sanjay Kalra, University of Alberta.
A protein exhibits toxic behaviour described as “prion-like” when it meets two essential criteria: firstly, it induces normally-folded proteins to change shape, adopting a toxic form; and secondly, it initiates a chain reaction, spreading throughout the nervous system. Prion diseases, including scrapie in sheep, mad cow disease in cattle, and Creutzfeldt-Jakob disease in humans, are well-known examples of this phenomenon.
There is a growing belief among researchers that a prion-like mechanism may contribute to the progression of ALS, and that the size and shape of the protein aggregates could influence their toxicity and spreading ability. Some even hypothesize that the shapes of the different aggregate may correlate with clinical symptoms, potentially explaining the varied symptoms observed in individuals with ALS.
With this award, Dr. Sim and her team will utilize sophisticated techniques, such as asymmetric flow field-flow fractionation, conformational stability assays, and real-time quaking conversion, to explore these hypotheses. These techniques will enable them to identify the specific shapes and sizes of misfolded proteins associated with ALS. More specifically, they will analyze brain tissue samples generously donated by eight individuals who had ALS, studying the complete size range of two common ALS-linked proteins, TDP-43 and SOD1. Their aim is to correlate the biophysical features of these proteins with clinical symptoms, ultimately hoping to pinpoint the most relevant protein structures that drive disease progression. This deeper understanding of the underlying mechanisms of ALS not only adds another crucial piece to the intricate ALS puzzle but also has the potential to open avenues for developing more targeted therapies.