Our laboratory is focused on characterizing biochemical and biophysical markers of bacterial cell death, with the goal of identifying novel means for treating infectious disease and combatting resistance formation based on the intrinsic response of the bacterium to lethal stress.
One core line of research involves developing synthetic biology platforms for exploring cell death physiology and triggering unique associated behaviors, using biomimicry of natural systems as a design blueprint. Most notably, we are interested in engineering RNA-based devices for detecting stress-enriched proteomes, stress-altered biochemistry, as well as tools for surveilling emergent ultrastructural properties induced by lethal perturbations.
Our other core line of work seeks to apply systems biology analysis methods towards advancing our understanding of how cytotoxic stress-induced physiological alterations impact the cell death process. In particular, we are interested in quantitatively determining how bioenergetic flux informs death phenotype appearance, and ultimately the kill kinetics of lethal perturbations.
Dwyer, D.J., Belenky, P., Yang, J.H., MacDonald, I.C., Martell, J.D., Takahashi, N., Chan, T.Y.C., Lobritz, M.A., Braff, D., Schwarz, E.G., Ye, J.D., Pati, M., Vercruysse, M., Ralifo, P.S, Allison, K.R., Khalil, A.S., Ting, A.Y., Walker, G.C. & Collins, J.J. (2014). Antibiotics induce redox-related alterations as part of their lethality. Proceedings of the National Academy of Science, 111(20): E2100-9.
Dwyer, D.J. & Winkler, J.A. (2013). Identification and characterization of programmed cell death markers in bacterial models. Methods in Molecular Biology, 1004, 145-159.
Dwyer, D.J., Camacho, D., Callura, J.M., Kohanski, M.A. & Collins, J.J. (2012). Antibiotic-induced bacterial cell death exhibits physiological and biochemical hallmarks of apoptosis. Molecular Cell, 46(5), 561-572.
Callura, J.M., Dwyer, D.J., Isaacs, F.J., Cantor, C.R. & Collins, J.J. (2010). Tracking, tuning and terminating bacterial physiology using synthetic riboregulators. Proceedings of the National Academy of Science, 107(36), 15898-15903.
Kohanski, M.A., Dwyer, D.J., Weirzbowski, J., Cottarel, G. & Collins, J.J. (2008). Protein mistranslation and two-component system activation trigger aminoglycoside-mediated hydroxyl radical formation and cell death. Cell, 135(4), 679-690.
Kohanski, M.A., Dwyer, D.J., Hayete, B., Lawrence, C.A. & Collins, J.J. (2007). A common mechanism of cellular death induced by bactericidal antibiotics. Cell, 130(5), 797-810.
Dwyer, D.J., Kohanski, M.A., Hayete, B. & Collins, J.J. (2007). Gyrase inhibitors induce an oxidative damage cellular death pathway in Escherichia coli. Molecular Systems Biology, 3, 91.
Isaacs, F.J., Dwyer, D.J. & Collins, J.J. (2006). RNA synthetic biology. Nature Biotechnology, 24(5), 545-554.
Isaacs, F.J., Dwyer, D.J., Ding, C., Pervouchine, D.D., Cantor, C.R. & Collins, J.J. (2004). Engineered riboregulators enable post-transcriptional control of gene expression. Nature Biotechnology, 22(7), 841-847.
Ph. D., Boston University, 2007