A declared goal of Systems Biology is to better understand and control biological complexity through the holistic integration of biological information on multiple biomolecular scales. This approach is applied to the development of global models that generate hypotheses related to biological processes or disease, which can be acutely tested experimentally. These models are often employed to predict the spatiotemporal dynamics of biological (e.g., genetic, metabolic) networks, and account for nonlinear behaviors arising from the concert of component activity.
Our research interests lie in the elucidation of design and operating principles underlying physiological remodeling that occurs upon integration of lethal stress signals. Relatedly, we are also interested in discovering how physiological remodeling informs susceptibility, tolerance or resistance to the cytotoxic effects of antibiotics. In particular, we are interested in quantitatively determining how bioenergetic flux impacts the kill kinetics of lethal perturbations and associated death phenotypes.
We are investigating the hypothesis that unique biological network behaviors triggered by lethal stress signals reveal physiological vulnerabilities that can be exploited to enhance current therapies. We are also investigating the hypothesis that protein expression is functionally and deterministically enriched in antibiotic-challenged pathogens thereby exposing physiological liabilities that can be capitalized on therapeutically. To address these questions, we are utilizing a multidisciplinary range of microbial genetics, computational, chemical and molecular biology techniques.