Network Biology and Drug Discovery

 

JAMES J. COLLINS

CENTER FOR BIODYNAMICS, CO-DIRECTOR

 

One of the defining challenges in systems biology is to determine the structures and mechanisms by which complex networks of genes, proteins and metabolites control cell processes and molecular dynamics. In this talk, we describe novel, integrated computational-experimental approaches that enable construction of quantitative models of gene-protein regulatory networks using expression measurements and no prior information on the network structure or function. We discuss how the reverse-engineered network models, coupled to experiments, can be used to identify the pathways and gene products targeted by pharmaceutical compounds, as well as the genetic mediators of different diseases. We describe how these network biology approaches led to the discovery that all classes of bactericidal antibiotics, regardless of drug-target interaction, induce a common oxidative damage cellular death pathway. We discuss how this discovery has changed our understanding of how antibiotics work, and established a viable means of enhancing existing antibiotics and limiting the emergence of resistance.