Ahmad S. Khalil, Ph.D.
Assistant Professor, Biomedical Engineering
B.S., Mechanical Engineering, Stanford University
M.S., Ph.D., Mechanical Engineering, Massachusetts Institute of Technology
Synthetic biology; systems biology; eukaryotic gene regulation; zinc fingers; programmable microfluidics; single-cell techniques; molecular biophysics & bioengineering.
Living cells encode a remarkable and diverse set of functions. Cells take in vast amounts of information about the environment, process the information, and make complex decisions about how to respond and direct new phenotypes. The functions that enable these sophisticated behaviors are programmed by circuits and assemblies of interacting genes and proteins. How are these molecular systems assembled and what specific functions do they encode? How do genetic circuits operate in response to dynamic cellular environments to program new phenotypes? Can we rewire and engineer these systems to program new cellular functions to help solve problems in biotechnology, energy, and health? To address these questions, we use a variety of experimental approaches, with special emphasis on the development of new synthetic and systems biology approaches. Notably, we build synthetic gene circuits in cells from well-understood components and study their functions. We also utilize engineering approaches to recapitulate dynamic cellular environments. We design and build programmable microfluidic devices that enable us to culture cells, program diverse environmental conditions, and monitor single cells. Because the problems we focus on are universal, we work with a range of organisms (bacteria, yeast, and mammalian cells).
Specific classes of problems we are interested in include:
1. Eukaryotic gene regulation. Elucidating the design principles of transcriptional regulatory systems and networks, which are responsible for controlling the thousands of genes in eukaryotic genomes. Programming eukaryotic transcription functions in cells through synthetic biology.
2. Phenotypic plasticity, evolution and engineering. Dissecting the regulatory systems that enable cells to adapt to fluctuating environments and generate new phenotypes. Exploring the environmental parameters that drive new phenotypes in individual cells using multiplexed microfluidic devices. Forward evolution of new and useful cellular functions. Studying drug tolerance mechanisms in bacteria and yeast.
Selected Recent Publications
Litcofsky NM, Afeyan RB, Krom RJ, Khalil AS, and Collins JJ. “Iterative Plug-and-Play Methodology for Constructing and Modifying Synthetic Gene Networks” Nature Methods. 9: 1077-80 (2012)
Khalil AS, Lu TK, Bashor CJ, Ramirez CL, Pyenson NC, Joung JK, and Collins JJ. “A Synthetic Biology Framework for Programming Eukaryotic Transcription Functions” Cell. 150: 647-658. (2012)
Borenstein JT, Tupper MM, Mack PJ, Weinberg EJ, Khalil AS, Hsiao J, and Garcia-Cardena G. “Functionalized Endothelialized Microvascular Networks with Circular Cross Sections in a Tissue Culture Substrate” Biomedical Microdevices. 12: 71-79. (2010)
Khalil AS, Appleyard DC, Labno AK, Georges A, Karplus M, Belcher AM, Hwang W, and Lang MJ. “Kinesin’s Cover-Neck Bundle Folds Forward to Generate Force” Proceedings of the National Academy of Sciences USA. 105: 19247-19232. (2008)
Khalil AS, Ferrer JM, Brau RR, Kottmann ST, Noren CJ, Lang MJ, and Belcher AM. “Single M13 Bacteriophage Tethering and Stretching” Proceedings of the National Academy of Sciences USA. 104: 4892-4897. (2007)