Benchtop Colony Arrayer for Accelerating Systems Biology Research in Prokaryotes

细菌感染，特别是大肠杆菌引起的细菌感染，仍然是一个主要的健康问题，据估计，全球卫生保健系统每年花费数十亿美元。这些感染的最大问题是它们在很大程度上是耐药性的，因此迫切需要开发新一代的抗菌剂。这仍然是一个缓慢的过程，部分原因是大多数还原论研究都集中在对单个组分进行编目，而不是了解在药物开发中至关重要的功能性重要细菌过程的全局途径结构。虽然这是一种合理的方法，但了解编码这些过程的基因如何相互作用，以及它们如何在介导强大的基本细菌功能的保守冗余途径中组织起来，对于治疗开发至关重要，即使在遗传上最易处理的模式生物如大肠杆菌中，治疗开发也非常有限。杆菌因此，大量潜在可行的药物靶点在很大程度上仍未被探索。拟议的研究计划旨在通过产生全面的功能（基因-基因或遗传）相互作用网络来促进发现可行的新抗菌药物靶标，这些网络可用于阐明临床相关核心生物过程（包括染色体分离和复制，核糖体生物发生，细胞分裂和转录调控）之间的基因功能和途径依赖性。NSERC通过研究工具和仪器计划的投资将允许系统地绘制这些遗传相互作用网络，以注释细菌基因并提供对细菌稳健性的见解-最终促进抗菌药物开发的细菌靶标的鉴定。该计划将有可能减轻加拿大医疗保健系统的经济负担，将里贾纳大学建立为相互作用组研究的国家中心，并将有助于保持加拿大在转化系统生物学研究方面的领先地位。

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.