Molecular Ligand Target Research Team

Exploring target molecules and mode-of-action of bioactive compounds through global analysis of chemical genetic interactions

Team Director

Charles M. Boone Ph.D.

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1989: Ph.D., McGill University, Canada
1993: Assistant Professor, Simon Fraser University, Canada
1997: Assistant Professor, Queen's University, Canada
2000: Associate Professor, University of Toronto, Canada
2003: Professor, University of Toronto, Canada
2008: Senior Visiting Scientist, RIKEN
2009: Team Leader, Molecular Ligand Target Research Team, RIKEN
2013: Team Director, Molecular Ligand Target Research Team, RIKEN Center for Sustainable Resource Science (-current)

Main Research Fields :	Biology
Related Research Fields :	Medicine, Dentistry & Pharmacy
Keywords :	Chemical Genomics / Target Identification / Yeast
Strategic Program :	Advanced Research and Technology Platforms

Outline

Bioactive molecular ligands with unique physiological effects must have specific cellular targets. Target identification is critical for elucidating the mechanism of action of molecular ligands and for drug discovery. However, drug target identification has been extremely difficult, because the interactions between molecular ligands and their targets are not uniform. Our team aims to develop innovative techniques for target identification based on the global analysis of yeast chemical-genetic and genetic interactions, leading to quick and accurate elucidation of ligand-target interactions.

Subjects

Global analysis of chemical genetic interactions between molecular ligands and their target molecules
Validating the mode of action of bioactive compounds
Identifying bioactive chemical tools and therapeutic leads that target essential gene pathways

A microarray-based method for identification of drug targets using the fission yeast ORFeome: We created a novel strain collection in a drug-sensitive genetic background that expresses the entire fission yeast ORFeome. We can now pool this library and grow the yeast in the presence of a drug. The abundance of each strain is assessed using DNA microarray to generate a genome-wide profile of drug-gene interactions. This chemical genomics approach can rapidly determine genes involved in pathways targeted by small molecules.