Research Project

Summary

This project consisted of large-scale ’basic science’ research.  The goal was to use functional and chemical genomic approaches to establish a comprehensive description of the biology of the budding yeast Saccharomyces cerevisiae. Researchers developed platforms to exploit this simple model organism to discover drug targets and understand the genetic basis of complex disease. The work principally used cutting-edge functional genomics to define gene function and to probe the mechanistic basis for drug action and the characterization of novel, unknown, and microbial proteins.

In their structural biology efforts, the project team identified the biochemical function of these proteins and formed hypotheses about their cellular role in microbial cells. This information has greatly extended fundamental knowledge about microbial biology and created an experimental basis for the Canadian biotech industry to develop anti-microbial drugs and biotechnological processes.

The team has made many valuable contributions to Canadian and Canadian-led commercial, educational, and scientific enterprises. For example, project leaders Aled Edwards and Cheryl Arrowsmith founded Affinium Pharmaceuticals, Mike Tyers helped set up MDS-Proteomics, and Charles Boone was a founder of Mycota Biosciences, which Merck recently purchased.

Moreover, the project has produced reagents and spurred development of technologies that have already produced patents and have attracted investment from the industrial sector. For example, the work inspired Singer Instruments to develop a table-top arraying robot which labs around the world are now acquiring. The team’s expertise in array-based genetics led collaborator Sasan Ragabazidah to create S&P Robotics, which markets a second-generation arraying robot for which the team’s lab built a prototype.  The team continues to identify significant market opportunities arising from the project.

Fast Facts

• Highlighted outcome: Genomic datasets and techniques valuable for development of human drugs, including many purified proteins, and of technologies to produce proteins and determine structures quicker and cheaper.
• Number of research personnel:  50.
• Number of peer-reviewed publications:  61 journal articles, 25 reviews or contributions to books, and 364 invited presentations.
• Number of patents:  2 published, 1 filed, and 1 provisional.
• Commercialization: 1 commercial license in place and 4 companies formed.

Notable Publications
Tong A, Lesage G, Bader G, Ding H, Xu H, Xin X, Young J, Berriz GF, Brost R, Chang Y,  Chen M,  Cheng X, Chua G, Friesen H, Goldberg DS, Haynes J, Humphries C,  He G, Hussein S, Ke L,  Krogan N, Li Z, Levinson JN, Lu H,  Ménard P, Munyana C, Parsons AB, Ryan O, TonikianR, RobertsT, Sdicu AM, ShapiroJ, SheikhB, Suter B, Wong SL,  Zhang LV, Zhu H, Burd CG, MunroS, SanderC, Rine J, GreenblattJ, PeterM, BretscherA, BellG, RothFP,  BrownG, Andrews BJ, Bussey H, and Boone C. 2004. Global  mapping of the  yeast  genetic  interaction  network.  Science.  303:808-13.

Mnaimneh S, Davierwala A, Haynes J, Moffat J, Peng W-T, Zhang W, Yang X, Pootoolal J, Chua G, Lopez A, Trochesset M, Morse D, Krogan N, Hiley S, Li Z, Morris Q, Grigull J, Mitsakakis N, Roberts CJ, Greenblatt J, Boone C, Kaiser C, Andrews BJ, and Hughes T. 2004. Exploration of essential gene functions via titratable promoter alleles. Cell 118:31-44.

Davierwala AP, Haynes  J, Li Z, Brost RL, Robinson MD, Yu L, Mnaimneh S, Preston N, Zhu H, Chen Y, Cheng X, Brown GW, Boone C, Andrews BJ, and Hughes TR. 2005.  The synthetic genetic interaction spectrum of essential genes. Nat.  Genet. 37:1147-52.

Gerstein M, Edwards AM, Arrowsmith CH, and Montelione GT. 2003.  Structural genomics: current progress. Science. 299:166.

Downey M, Houlsworth R, Rolli A, Brehme M, Galicia S, Guilard S, Zubko MK, Krogan N, Emili A, Greenblatt  J, Harrington L, Lydall D, and Durocher D. 2006. A genome-wide screen identifies the evolutionarily conserved KEOPS complex as a telomere regulator. Cell 124: 1155-68.