Research Interests

My research focuses on engineering next-generation genetic circuits using the tools of systems and synthetic biology. This approach is built upon the synergistic combination of the forward engineering of small genetic modules (synthetic biology) and the reverse engineering of the complex native networks of their microbial hosts (systems biology)—with the ultimate goal of integrating these approaches to produce higher-order programs. These programs will be tailored to address emerging applications in biotechnology, with recent focus areas including biopixel sensor arrays, microbial cancer therapy and diagnosis, and genetic frequency multiplexing (see below).

Research Highlights

(1) A sensing array of radically coupled genetic 'biopixels'. [Nature 2012]

I used synergistic modes of communication—quorum sensing via dissolved AHL and redox signaling via H2O2 vapor—to enable the synchronization of genetic clocks across centimeter length scales. I used this platform to construct an LCD-like macroscopic "biopixel" array used to sense arsenic via modulation of the oscillatory period. This work received substantial attention including an F1000 evaluation, Nature News & Views commentary, and media coverage from MSNBC, CNET, L.A. Times, Popular Science and others.












(2) Clinical applications for cancer therapy and diagnostics. [Science Translational Medicine 2014 (in review), ACS Synthetic Biology 2012, ACS Synthetic Biology 2012]

I expanded the use of genetic circuits to Salmonella typhimurium and the probiotic bacterium E. coli Nissle 1917 to tackle clinical applications in cancer diagnostics and therapy. This work represents a key step toward realizing synthetic biology applications—moving into microbial species beyond lab strains of E. coli. As part of this research, I initiated a collaboration with Dr. Sangeeta Bhatia and spent 3 months at the MIT Koch Institute studying in vivo gene circuits in mouse models of cancer. During this period, in collaboration with Tal Danino, I proposed a new project on engineered probiotics for point-of-care cancer diagnostics.












(3) Rapid and tunable post-translational coupling of genetic circuits. [Nature 2014]

I used competitive coupling to post-translationally link two independent genetic clocks across the single-cell, colony, and multi-colony scales. Using this platform, I constructed a multispectral encoding circuit whereby frequency-modulated oscillations from both clocks are combined into a single time series, thus enabling the extraction of the dynamics of multiple underlying networks via the measurement of a single reporter. In addition, through integration with host signaling processes, I used the clock network to uncover novel regulation in the host stress response to H2O2.











Commentaries

Synthetic biology at all scales. [Trends in Biotechnology 2013]

SB6.0: The sixth international meeting on synthetic biology. [ACS Synthetic Biology 2013 (to appear)]

The first annual winter q-bio meeting: Quantitative biology on the Hawaiian islands. [ACS Synthetic Biology 2013]

Making gene circuits sing. [Proceedings of the National Academy of Sciences 2012]

Stochastic emergence of groupthink. [Science 2010]

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