Grant: Research Tools and Instruments

1. Research programs to be supported (Intended use). ***The applicants (Boraston, Boulanger, Reynolds and Burke) share a common interest in understanding the molecular basis of how bio-molecular interactions mediate fundamental cellular processes. Through previous investments from CFI and NSERC RTI they have amassed state of the art biophysical facilities for X-ray crystallography (XRC), mass spectrometry (MS), isothermal titration calorimetry (ITC), and biochemical assays. This collaborative structural and biophysical facility is a major strength, and is one of the most productive in Canada. ******The proposed research programs are diverse including microbial pathogenesis (Boraston, Boulanger, Reynolds and Burke), host-microbiome interactions (Reynolds), generation of novel biofuels (Boraston), and cancer signalling (Burke, Boulanger). Fundamental to almost all of these studies is the measurement of molecular interactions, specifically protein-protein, protein-small molecule, and protein-carbohydrate interactions in a high throughput manner.******2. Equipment requested and cost (1 x Octet K2 system at $138,931). We are requesting a state of the art Octet bio-layer interferometry system that will allow for the rapid determination and quantitation of bio-molecular interactions. The following specifications are critical:***#1 Throughput. The proposed applicants are working on ~50 protein targets at any given time, with a major goal being the characterisation of the molecular interactions each protein can form. Having a platform that allows for the rapid characterisation of protein-protein, protein-carbohydrate, and protein-membrane interactions is essential, while only needing small amounts of protein. ***#2 Capability to study binding in complex mixtures. Key to our analysis of bio-molecular interactions is the capability to characterise molecular interactions in complicated mixtures, including membrane mixtures, and biological samples. The Octet K2 system is able to measure affinities within extremely complicated samples, including cellular lysates.******3. Relationship to other funding. All of the applicants are currently supported by both NSERC Discovery grants and CIHR operating grants. This funding does not allow for infrastructure purchase. The Octet system requested will provide critical support to this research portfolio. This infrastructure will also be essential to support current and future projects with both industrial and governmental partners, for example Zymeworks (Boulanger), Alectos (Boraston, Boulanger), ARC Medical Devices (Boraston), and HHMI (Burke). ******4. Need. There is an urgent need for the proposed, highly flexible instrumentation to monitor bio-molecular interactions. There currently is no equipment that allows for the rapid characterisation of bio-molecular interactions. This requested infrastructure will be essential for the continued success of structural and biophysical research at the University of Victoria. **