$75,000 awarded to Monika Schmidt in the lab of Dr. Christopher Pearson at The Hospital for Sick Children.
Genetic mutations can take on many forms. Some are deleted portions of a gene, some are simply wrong pieces substituting for the right ones and some are additions, where a gene becomes longer with excess, unnecessary pieces inserted, making it oversized and dysfunctional. In 2011, the most common genetic cause of ALS was discovered. This gene, called C9orf72, can be abnormally elongated, causing it to be dysfunctional and lead to motor neuron degeneration, but the exact mechanisms that confer ALS are not yet fully understood. When this gene grows in length, it forms unusual shapes that our natural defense mechanisms attempt to repair. However, it is believed that in the case of C9orf72, our DNA repair may actually make things worse.
With funding from ALS Canada, Monika Schmidt will pursue this topic for her PhD work in the lab of Dr. Christopher Pearson at The Hospital for Sick Children. Previous work in the Pearson lab has demonstrated that a substance in our DNA repair system, called MutSb, which is particularly good at fixing some types of genetic errors, is particularly bad at causing elongated gene mutations to have even worse effects, including making them even longer and possibly triggering disease.
Monika will examine how MutSb may play a role in making C9orf72 toxic, or in enhancing its toxicity by looking at their specific interaction. The work will include examining the connection both in laboratory cells and in a recently created mouse model of C9orf72 ALS, and could potentially identify MutSb as a therapeutic target for future treatment. Ultimately, Monika’s work represents a very novel avenue of research in the field and we look forward to learning of her results as they emerge.