Associate Professor of BioSciences
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.
Pubmed Search for articles by M Bennett
Sousa FL, Parente DJ, Shis DL, Hessman JA, Chazelle A, Bennett MR, Teichmann AS & Swint-Kruse L, “AlloRep: a repository of sequence and mutagenesis data for LacI/GalR transcription regulators.” J Mol Biol 428, 671-678 (2016).
Chen Y, Kim JK, Hirning AJ, Josić K & Bennett MR, “Emergent genetic oscillations in a synthetic microbial consortium.” Science 349, 986-989 (2015).
Veliz-Cuba A, Hirning AJ, Atanas AA, Hussain F, Vancia F, Josić K & Bennett MR, “Sources of noise in a synthetic gene oscillator.” PLOS Comp. Biol. 11, e1004674 (2015).
Kim JK, Josić K & Bennett MR, “The relationship between stochastic and deterministic quasi-steady state approximations.” BMC Syst. Biol. 9, 87 (2015).
Nguyen-Huu TD, Gupta C, Ma B, Ott W, Josić K & Bennett MR, “Timing and variability of galactose metabolic gene activation depend on the rate of environmental change.” PLOS Comput. Biol. 10, e1004399 (2015).
Hussain F, Gupta C, Hirning AJ, Ott W, Matthews KS, Josic K, Bennett MR. Engineered temperature compensation in a synthetic genetic clock. Proc Natl Acad Sci USA, 111(3) 2014: 972-977
Gupta C, Lopez JM, Azencott R, Bennett MR, Josic K & Ott, W Modeling delay in genetic networks: From delay birth-death processes to delay stochastic differential equations. J Chem Phys, 140 2014: 204108
Shis DL, Hussain F, Meinhardt S, Swint-Kruse L & Bennett MR Modular, multi-input transcriptional logic gating with orthogonal LacI/GalR family chimeras. ACS Synthetic Biology, 3 2014: 645-651
Kim JK, Kilpatrick ZP, Bennett MR & Josic K Molecular mechanisms that regulate the coupled period of the mammalian circadian clock. Biophys J, 106 2014: 2071-2081
Shis DL & Bennett MR The many facets of T7 RNA polymerase. Mol Syst Biol, 10 2014: 745
Kim JK, Josic K & Bennett MR The validity of quasi-steady-state approximations in discrete stochastic simulations. Biophys J, 107 2014: 783-793
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
Masiello, C. A., Gao, X., Chen, Y., Bennett, M. R., Zygourakis, K., Rudgers, J., Liu, S., Wagner, D. & Silberg, J. J. Biochar and microbial signaling: Production conditions determine effects on microbial communication. Environmental Science and Technology, 47 2013: 11496-11503
Razinkov, I. A., Baumgartner, B. L., Bennett, M. R., Tsimring, L. S., & Hasty, J. Measuring competitive fitness in dynamic environments. Journal of Physical Chemistry B, 117 2013: 13175-13181
Gupta, C., Lopez, J. M., Ott, W., Josic, K. & Bennett, M. R. Transcriptional delay stabilizes bistable gene networks. Physical Review Letters, 111 2013: 058104
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