Grant: Research Tools and Instruments

<p>A critical bottleneck in the path of translating a genomic discovery to medicine is that it is not apparent or easily deducible how gene mutations result in aberrant changes in protein function and the accompanying protein-protein interaction (PPI) or regulatory network. To overcome this limitation, it is critical to devise facile and robust strategies to decode the functional proteome that drives disease initiation and progression. Peptide array is a powerful method by which to interrogate the function and connectivity of proteins in health and disease. The ability to synthesize thousands of peptides directly on cellulose membranes has brought transformative changes in proteomics. Dr. Li and the co-applicants, Drs. Litchfied, O&rsquo;Donoghue and Shilton, have been conducting cutting edge research in proteomics and chemical biology which is dependent, in large part, on peptide arrays and soluble peptides. It is essential that this group of productive and innovative scientists to have access to the state-of-the-art instrumentation in peptide and peptide array synthesis in order for them to conduct cutting edge research in proteomics and related fields.</p> <p>The requested infrastructure, the MultiPep RSi Automated Peptide Synthesizer, will directly enhance our research capacity and empower a productive team that has achieved research excellence and gained international acclaim in functional proteomics. The principal applicant, Dr. Li&rsquo;s research is focused on the characterization of protein function and defining how changes in the PPI network underlies complex human diseases such as cancer. Dr. Li&rsquo;s group pioneered the use of peptide arrays to define modular domain specificity and map PPI in a high throughput fashion. Dr. Litchfield is a world-renowned expert in kinase signaling. His paradigm-shifting discovery that casein kinase 2 (CK2) regulates apoptosis by phosphorylating caspase substrates was only made possible by an innovative peptide array screening. Dr. O&rsquo;Donoghue has developed new ways by which to encode phosphorylated Ser in a site-specific manner. This would allow the production of fully active kinases for biochemical and functional characterization. Peptide arrays will facilitate these studies by providing an efficient, high-throughput platform for kinase substrate characterization and inhibitor identification. Dr. Shilton is researching into the molecular basis of PIN1 and other proteins. Once again, ready access to peptide and peptide array synthesis has played a critical role in Dr. Shilton's research program. Due to the high throughput nature of these research programs, a peptide synthesizer with high-capacity and multiple functions is required. Conversely, the lack of such an equipment would significantly compromise the innovative research programs of the applicants.</p>