Research Project

Summary

This project aimed to provide a comprehensive view of protein and genetic interactions in biomedically important model systems - bacteria, mouse, worm, and yeast.

For the bacterial, worm, and yeast  components, the  team used a range  of ‘cutting-edge’ approaches from functional genomics  to define gene function in model eukaryotic organisms and to characterize novel protein complexes in bacteria and yeast.  The genetic network and other yeast functional genomics projects may well unravel the basis of genetic disease and also lead to discovery of new compounds that might assist in treating proliferative disorders such as cancer.

The Functional Annotation of the Mouse Genome project has moved Canada’s mouse genomics to the forefront of this rapidly growing and increasingly important field. The project team has generated mouse models for human conditions such as kidney disease and osteoporosis, developed new tools to help characterize Canada’s mutant mice, and established new mouse cell lines that are in high demand from academic and industrial investigators worldwide.

The Mammalian Protein-Protein Interactions project team developed high-throughput approaches for quantitatively assessing protein-protein interactions in mammalian cell systems. Because most regulated cellular processes take place via complex protein-protein interaction networks, many human diseases originate with mutations that interfere with the assembly or function of these networks.

With the successful completion of this program, these approaches now promise to provide major insights into human pathologies and highlight effective targets for therapeutic development.

Fast Facts

• Highlighted outcome:  Major insights into the molecular causes of a wide range of human diseases and new targets for drug and biomarker development.
• Number of research personnel:  191.
• Number of peer-reviewed publications:  98 referred papers (including in Nature and Science), 17 invited reviews, 3 book chapters or contributions to collective works, and over 385 invited presentation.
• Patents: 1 provisional patent, 1 patent filed, 2 published patents, 1 commercial license in place, and 4 companies formed (Affinium Pharmaceuticals, MDS-Proteomics, Mycota BioSciences, and Virtek Proteomics).

Notable Publications
Butland G, Peregrin-Alvarez JM, Li J, Yang W, Yang X, Canadien V, Starostine A, Richards D, Beattie B, Krogan N, Davey M, Parkinson J, Greenblatt J, and Emili A. 2005.  Interaction network containing conserved and essential protein complexes in Escherichia coli. Nature.  433(7025):531-7.

Tong AH, Lesage G, Bader GD, Ding H, Xu H, Xin X, Young J, Berriz GF, Brost RL, Chang M, Chen Y, 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, Menard P, Munyana C, Parsons AB, Ryan O, Tonikian R, Roberts T, Sdicu AM, Shapiro J, Sheikh B, Suter B, Wong SL, Zhang LV, Zhu H, Burd CG, Munro S, Sander C, Rine J, Greenblatt J, Peter M, Bretscher A, Bell G, Roth FP, Brown GW, Andrews B, Bussey H, and Boone C. 2004.  Global mapping of the yeast genetic interaction network. Science. 303(5659):808-13.

Krogan NJ, Cagney G, Yu H, Zhong G, Guo X, Ignatchenko A, Li J, Pu S, Datta N, Tikuisis AP, Punna T, Peregrin-Alvarez JM, Shales M, Zhang X, Davey M, Robinson MD, Paccanaro A, Bray JE, Sheung A, Beattie B, Richards DP, Canadien V, Lalev A, Mena F, Wong P, Starostine A, Canete MM, Vlasblom J, Wu S, Orsi C, Collins SR, Chandran S, Haw R, Rilstone JJ, Gandi K, Thompson NJ, Musso G, St Onge P, Ghanny S, Lam MH, Butland G, Altaf-Ul AM, Kanaya S, Shilatifard A, O'Shea E, Weissman JS, Ingles CJ, Hughes TR, Parkinson J, Gerstein M, Wodak SJ, Emili A, and Greenblatt JF. 2006.  Global landscape of protein complexes in the yeast Saccharomyces cerevisiae. Nature. 440(7084):637-43.

Mnaimneh S, Davierwala AP, Haynes J, Moffat J, Peng WT, Zhang W, Yang X, Pootoolal J, Chua G, Lopez A, Trochesset M, Morse D, Krogan NJ, Hiley SL, Li Z, Morris Q, Grigull J, Mitsakakis N, Roberts CJ, Greenblatt JF, Boone C, Kaiser CA, Andrews BJ, and Hughes TR. 2004.  Exploration of essential gene functions via titratable promoter alleles. Cell 118(1):31-44.

Barrios-Rodiles M, Brown KR, Ozdamar B, Bose R, Liu Z, Donovan RS, Shinjo F, Liu Y, Dembowy J, Taylor IW, Luga V, Przulj N, Robinson M, Suzuki H, Hayashizaki Y, Jurisica I, and Wrana JL. 2005.  High-throughput mapping of a dynamic signaling network in mammalian cells. Science. 307(5715):1621-5.