Matthew Bennett

Assistant Professor of Biochemistry and Cell Biology

My research generally spans the boundary between experimental and theoretical molecular systems biology. I am particularly interested in the dynamics of gene regulation - from small-scale interactions such as transcription and translation, to the large-scale dynamics of gene regulatory networks. I use a hybrid experimental and computational approach to uncover the underlying design principles governing native gene networks and to use these concepts to design novel synthetic circuits. The ultimate goal of synthetic biology is the creation of practical, engineered genetic circuits for medical and industrial applications. Critical to this goal is the elucidation of the fundamental mechanisms that govern gene regulation at all levels. To this end, my work has focused on the kinetic properties of both synthetic networks, such as gene oscillators, and native regulatory networks, such as the galactose utilization pathway in S. cerevisiae.

Currently, my lab uses both bacteria and yeast as model organisms to study genetic signaling networks, which are central to cellular decision-making processes. By detecting and interpreting dynamic cues, these networks enable cells to adapt to their surroundings in a context-dependent manner. We want to know: 1) how information is relayed from one genetic module to the next; 2) how network architecture determines the fidelity of the signal; and 3) how problems arising from network deficiencies or deleterious mutations might be alleviated.

The work in my lab is highly interdisciplinary, combining aspects of synthetic biology, microfluidic engineering, and theoretical physics. Synthetic biology is used to create novel gene circuits as well as perturb naturally occurring gene networks. These networks are then examined at the single-cell level with the aid of microfluidic devices that allow for the precise control over environmental conditions. Finally, mathematical models are used to understand the observed phenomenon and aid in the design of future synthetic gene networks.

Publications

Shis, D. L. & Bennett M. R. A library of synthetic transcriptional AND gates built with split T7 RNA polymerase mutants.  Proc Natl Acad Sci USA, 110 2013: 5028-5033

Nevozhay, D., Adams, R. M., Van Itallie, E., Bennett, M. R. & Balázsi, G. Mapping the environmental fitness landscape of a synthetic gene circuit.  PLoS Comp Biol, 8 2012: e1002480

O’Brien, E. L., Van Itallie, E., Bennett, M. R. Modeling synthetic gene oscillators.  Math Biosci, 236 2012: 1-15

Schmidt, C.M., Shis, D. L., Nguyen-Huu, T. D. & Bennett, M. R. Stable maintenance of multiple plasmids in E. coli using a single selective marker.  ACS Synthetic Biology, 1 2012: 445-450

Baumgartner, B. L., Bennett, M. R., Ferry, M., Johnson, T., Tsimring, L. S. & Hasty, J. Antagonistic gene transcripts regulate adaptation to new growth environments.  Proc. Natl. Acad. Sci. USA, 108 2011: 21087-21092

Josić, K., Lopez, J. M., Ott, W. R., Shiau, L. & Bennett, M. R. Stochastic delay accelerates signaling in gene networks.  PLoS Comp. Biol., 7 2011: e1002264

Pena, M., Van Itallie, E., Bennett, M.R., & Shamoo, Y. Evolution of a single gene highlights the complexity underlying molecular descriptions of fitness.  CHAOS, 20 2010: 026107

Pena, M., Davlieva, M., Bennett, M.R., Olson, J., and Shamoo, Y. Evolutionary fates within a microbial population highlight an essential role for protein folding during natural selection.  Mol Syst Biol, 6 2010: 387

Mather, W., Bennett, M.R., Hasty, J., and Tsimring, L.S. Delay-induced degrade-and-fire oscillations in small genetic circuits.  Phys Rev Lett, 102 2009: 068105

Bennett, M.R. and Hasty, J. Microfluidic devices for measuring gene network dynamics in single cells.  Nature Reviews Genetics, 10 2009: 628-638

Bennett, M.R. and Hasty, J. Overpowering the component problem.  Nat Biotech, 27 2009: 450-451

Stricker, J., Cookson, S., Bennett, M.R., Mather, W.H., Tsimring, L.S., and Hasty, J. A fast, robust and tunable synthetic gene oscillator.  Nature, 456 2008: 516-519

Bennett, M.R. and Hasty, J. Genome rewired.  Nature, 452 2008: 824-825

Bennett, M.R., Pang, W.L., Ostroff, N.A., Baumgartner, B.L., Nayak, S., Tsimring L.S., and Hasty, J. Metabolic gene regulation in a dynamically changing environment.  Nature, 454 2008: 1119-1122

Handel, A. and Bennett, M.R. Surviving the bottleneck: Transmission mutants and the evolution of microbial populations.  Genetics, 180 2008: 2193-2200

Bennett, M.R. and Hasty, J. A DNA methylation-based switch generates bistable gene expression.  Nat Genet, 39 2007: 146-147

Grilly, C., Stricker, J., Pang, W.L., Bennett, M.R., and Hasty, J. A synthetic gene network for tuning protein degradation in Saccharomyces cerevisiae.  Mol Sys Bio, 3 2007: 127

Lu, T., Shen, T., Bennett, M.R., Wolynes, P.G., and Hasty, J. Phenotypic variability of growing cellular populations.  Proc Natl Acad Sci USA, 104 2007: 18982-18987

Bennett, M.R., Volfson, D., Tsimring, L., and Hasty, J. Transient dynamics of genetic regulatory networks.  Biophys J, 92 2007: 3501-3512

Lindner, J.F., Bennett, M., and Wiesenfeld, K. Potential energy landscape and finite-state models of array-enhanced stochastic resonance.  Phys Rev E, 73 2006: 031107

Bennett, M.R. and Wiesenfeld, K. Towards a unified rate theory of stochastic resonance.  Fluct Noise Lett, 6 2006: L405-L413

Lindner, J.F., Bennett, M., and Wiesenfeld, K. Stochastic resonance in the mechanoelectrical transduction of hair cells.  Phys Rev E, 72 2005: 051911

Bennett, M. and Wiesenfeld, K. Averaged equations for distributed Josephson junction arrays.  Physica D, 192 2004: 196-214

Bennett, M., Wiesenfeld, K., and Jaramillo, F. Stochastic resonance in hair cells.  Fluct Noise Lett, 4 2004: L1-L10

Bennett, M., Schatz, M.F., Rockwood, H., and Wiesenfeld, K. Huygens' clocks.  Proc Roy Soc London A, 458 2002: 563-579