HENRY KRAUSE

Zebrafish HTS platforms for nuclear receptor related drug discovery and pathway elucidation

 

Competition: CQDM / CIHR Program 2014
Funding: $1,000,000 / 2 years
Beginning: July 2015

Drug discovery is a long and expensive process, and many potential drugs discovered by traditional screening using cells in petri dishes fail in late development or after approval due to unforeseen side effects. Henry Krause’s team has developed a novel drug screening platform that can visualize potential drug activity three-dimensionally in live animal tissues, and can then isolate the active drugs or metabolites from the responding tissues. This transgenic zebrafish platform specifically targets a family of human proteins called nuclear receptors implicated in responding to various hormones. Nuclear receptors, one of the most highly responsive families of proteins for drug targeting, control processes such as metabolism, growth and behaviour, and diseases such as diabetes, Parkinson’s, Alzheimer’s and cancer. The team’s objective is to develop a zebrafish platform spanning the whole panel of the 48 human nuclear receptors as well as 6 epigenetic-regulating cofactors. Embryos from these fish can be collected by the thousands and screened rapidly against an equal number of drug candidates, an important feature enabling the screening of the large libraries of compounds that pharmaceutical companies have developed. The active compounds cause the fish to glow green, which further facilitates identifying hits. In addition to further testing these compounds for drug potential, Dr. Krause’s team 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. This new more accurate, rapid and cost effective screening process aims at enabling and accelerating the development of new drugs.

Henry Krause

University of Toronto

Co-Investigators

Vincent Giguère
McGill University

Jens Tiefenbach
InDanio Bioscience