Investigating protein aggregation with small molecules

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Research Summary: Among the many and diverse proteins in mammals, some proteins can misfold and form aggregates. Studies indicate that these partially disordered protein aggregates can be toxic to cells. However the exact nature of protein misfolding and aggregation is still a work in progress. In our proposal we are aiming to answer these questions, by using small molecules as tools to study the mechanisms of protein aggregation. Small molecule libraries will be synthesized and biochemical studies will be conducted to monitor protein aggregation kinetics by a number of techniques. These studies will assist in elucidating the critical regions involved in protein aggregation at the molecular level. Furthermore, these investigations will be supported by computational modeling to determine the nature of protein-small molecule interactions and their role in protein aggregation/disaggregation. We anticipate that these studies will advance our current knowledge by elucidating the mechanisms of protein aggregation pathway and will assist in developing novel tools to study protein aggregation. **HQP training: Our proposed research program will train several graduate and undergraduate students over the next five years. Students will be trained in a number of research techniques which will provide the necessary skill sets to succeed in academic or industrial settings as future scientists and contribute to the growth of scientific and economic landscape in Canada.