Grant: Research Tools and Instruments - Category 1 (<$150,000)

Bacterial infections, especially those due to Escherichia coli, remain a major health concern and are estimated to cost health care systems worldwide billions of dollars annually. The greatest concern of these infections is the fact that they are largely antibiotic-resistant, and hence there is an urgent need to develop a new generation of antimicrobials. This remains a slow process, partly because most reductionist studies have focused on cataloguing individual components rather than understanding the global pathway architecture of the functionally important bacterial processes that are of vital interest in drug development. While this is a legitimate approach, understanding how genes encoding these processes interact with each other and how they are organized in conserved redundant pathways mediating robust essential bacterial functions is critical for therapeutic development, which has so far been quite limited, even in the most genetically tractable model organisms like E. coli. Consequently, a significant number of potentially viable drug targets remain largely unexplored. The proposed research program aims to facilitate discovery of viable new antimicrobial drug targets by generating comprehensive functional (gene-gene, or genetic) interaction networks that are useful for elucidating gene functions and pathway dependencies among clinically relevant core biological processes including chromosome segregation and replication, ribosome biogenesis, cell division, and transcriptional regulation. Investment by the NSERC through the Research Tools and Instruments Program will allow systematic mapping of these genetic interaction networks for annotating bacterial genes and providing insights into bacterial robustness - ultimately facilitating the identification of bacterial targets for antimicrobial drug development. This program will potentially lessen the economic burden on the Canadian health care system, establish the University of Regina as a national hub for interactome research, and will help maintain Canada's leading position in translational systems biology research.