Grant: Discovery Grants Program - Individual

Life at the molecular level is a dynamic world, where the key players - proteins, oligonucleotides, lipids, and carbohydrates - are in a perpetual state of structural flux, shifting rapidly between structural configurations in a process known as 'conformational dynamics'. For a good long time, while we were transfixed by the beautiful (yet entirely static) pictures of protein structure provided by X-ray crystallography, the assumption was that these 'dynamics' were of at best limited interest to protein function. However, over the past few decades, it has become increasingly clear that how proteins move is just as important as how proteins look. Simply put, if proteins hadn't evolved to move in certain highly specific ways, most would be completely non-functional and life as we know it would be completely impossible. Since its inception in 2007, the Wilson group discovery program has earned international recognition for the exploration of conformational dynamics as a driver of protein (mis)function, with high impact discoveries in catalysis, protein interactions and protein misfolding enabled by unique, self-developed bioanalytical technologies. We have have also been uniquely successful at translating this seemingly 'academic' discovery research to real-world applications in collaboration with a host of industrial partners. The current proposal builds on our discovery program success to advance a deeper exploration of dynamic protein function, with potential breakthroughs revealing how proteins evolve functional efficiency, selectivity and allosteric networks. We will introduce new mass spectrometry-based bioanalytical technologies that will transform the process of therapeutic and vaccine development (NSERC DG eligible as bioanalytical technology and process development) and delve even more deeply into the physicochemical mechanisms that drive protein (mis)function and evolution. The Wilson group discovery program has three overarching, long-term objectives: (i) To meaningfully advance our understanding of the physicochemical drivers of protein (mis)function and the mechanisms of dynamic protein evolution. (ii) To develop new bioanalytical tools that enable deeper explorations of protein dynamics and the incorporation of structural dynamics information into therapeutics and vaccine development pipelines. (iii) To provide an unparalleled, equitably accessible training experience for future scientific leaders in Canada.