Grant: Operating Grant: CQDM/CIHR Collab Prog in Personalized Medicine -full appl

Drug discovery is a long and expensive process, and many potential drugs discovered by traditional screening fail in late development or after approval due to unforeseen side effects. Pharmaceutical companies are looking for new ways to make the screening process more accurate, rapid and costeffective. We have developed a novel, live-animal, drug screening platform that can visualize potential drug activity three-dimensionally in live tissues, and can then isolate the active drugs or metabolites from responding tissues. Our transgenic zebrafish platform specifically targets a family of human proteins called nuclear receptors. Nuclear receptors control processes such as metabolism, growth and behaviour, and diseases such as diabetes, Parkinson’s, Alzheimer’s and cancer. Fortunately, nuclear receptors are one of the most highly amenable families of proteins for drug targeting. Each of the 52 transgenic fish lines that we are making represents a different nuclear receptor (or cofactor). Embryos from these fish can be collected by the thousands, and screened rapidly against an equal number of candidate drugs. Active compounds cause the fish to glow green. In addition to further testing of these compounds for drug potential, we will also use them to identify their target genes and disease pathways. This collaboration brings an innovative approach to drug discovery and genome-wide pathway analysis that will benefit both the pharmaceutical industry and patients by enabling and accelerating new drug discovery and the development of safer and more effective disease management options.