Cells use molecular networks to process information from the environment and program new phenotypic behaviors in response to these extrinsic signals. The long-term goal of our research is to understand how these complex networks assemble and function to give rise to important cellular behaviors, like growth, development, response to stress, and communication. In turn, we use these natural design principles as inspiration to engineer cellular systems for therapeutic and other benefit.
We use and develop a variety of quantitative biology and engineering approaches. Notably, we use synthetic biology to build genetic circuits in cells from well-understood biological components. By building or manipulating genetic circuits, we hope to elucidate the design logic and function of these systems from the bottom-up, as well as provide new tools for rationally engineering cells. We also develop advanced fluidic technologies, like microfluidic devices, to study cells in complex environmental conditions. These tools allow us to study how a genetic circuit operates in response to dynamic cellular environments, as well as how cellular systems rewire and adapt to enable diversification and survival in fluctuating environments. Along with these novel approaches, we employ theoretical modeling, genomics, and systems biology to help us build links between molecules, circuits, and cellular behavior. Because the problems we focus on are universal, we work with a range of organisms, including bacteria, yeast, and mammalian cells.
Using Targeted Chromatin Regulators to Engineer Combinatorial and Spatial Transcriptional Regulation
Albert J. Keung, Caleb J. Bashor, Szilvia Kiriakov, James J. Collins and Ahmad S. Khalil
Cell, 158: 110-120 (2014)
Antibiotics Induce Redox-Related Physiological Alterations as Part of Their Lethality
Daniel J. Dwyer, Peter A. Belenky, Jason H. Yang, I. Cody MacDonald, Jeffrey D. Martell, Noriko Takahashi, Clement T. Y. Chan, Michael A. Lobritz, Dana Braff, Eric G. Schwarz, Jonathan D. Ye, Mekhala Pati, Maarten Vercruysse, Paul S. Ralifo, Kyle R. Allison, Ahmad S. Khalil, Alice Y. Ting, Graham C. Walker and James J. Collins
Proc. Natl. Acad. Sci. USA, 111: E2100-E2109 (2014)
Iterative Plug-and-Play Methodology for Constructing and Modifying Synthetic Gene Networks
Kevin D. Litcofsky, Raffi B. Afeyan, Russell J. Krom, Ahmad S. Khalil* and James J. Collins* (*Co-corresponding)
Nature Methods, 9: 1077-80 (2012)