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Matthew Bennett Associate Professor Associate Professor of BioSciences e-mail:[email protected] Ph.D. Physics (2006) Georgia Institute of Technology, Atlanta GA B.S. Physics (2000) Georgia Institute of Technology, Atlanta GA Primary Department Department of BioSciences Department Affiliations Department of Bioengineering Institute of Biosciences and Bioengineering Systems, Synthetic, and Physical Biology Other Affiliations Baylor College of Medicine MD Anderson Websites The Bennett Lab Website Research Areas Synthetic Biology, Cellular Signaling, Computational Biology, Microfluidic Engineering Research Statement 2009 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. Teaching Areas Computational Biology Selected Publications Refereed articles Sousa FL, Parente DJ, Shis DL, Hessman JA, Chazelle A, Bennett MR, Teichmann AS & SwintKruse 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). Gomez MM, Murray RM & Bennett MR, “The effects of time-varying temperature on delayed gene networks.” Submitted (2015). Gomez MM, Sadeghpour M, Bennett MR, Orosz G & Murray RM, “Stochastic delays in genetic regulatory networks: A distribution-based stability analysis.” Submitted (2015). Kim JK, Josić K & Bennett MR, “The relationship between stochastic and deterministic quasisteady 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). 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). 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. 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. Kim JK, Josic K & Bennett MR "The validity of quasi-steady-state approximations in discrete stochastic simulations." Biophys J, 107 (2014) : 783-793. 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, 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. Gupta, C., Lopez, J. M., Ott, W., Josic, K. & Bennett, M. R. "Transcriptional delay stabilizes bistable gene networks." Physical Review Letters, 111 (2013) : 058104. 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. 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., 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. 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. Bennett, M.R. and Hasty, J. "Microfluidic devices for measuring gene network dynamics in single cells." Nature Reviews Genetics, 10 (2009) : 628-638. 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., 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. 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., Volfson, D., Tsimring, L., and Hasty, J. "Transient dynamics of genetic regulatory networks." Biophys J, 92 (2007) : 3501-3512. 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. 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. "Potential energy landscape and finite-state models of array-enhanced stochastic resonance." Phys Rev E, 73 (2006) : 031107. 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. Articles Shis DL & Bennett MR "The many facets of T7 RNA polymerase." Mol Syst Biol, 10 (2014) : 745. Bennett, M.R. and Hasty, J. "Overpowering the component problem." Nat Biotech, 27 (2009) : 450-451. Bennett, M.R. and Hasty, J. "Genome rewired." Nature, 452 (2008) : 824-825. Bennett, M.R. and Hasty, J. "A DNA methylation-based switch generates bistable gene expression." Nat Genet, 39 (2007) : 146-147. Presentations Invited Talks “Dynamics of synthetic microbial consortia.” QCBNet Workshop: Quantifying Cellular Dynamics – Challenges and Solutions, Half Moon Bay, CA. “Synthetic microbial consortia.” Seminar, Center for Theoretical Biophysics, Rice University, Houston, TX. “Engineering multicellular systems in bacteria.” Winter q-Bio Conference, Maui, HI. “Synthetic microbial consortia.” Seminar, Laufer Center and Department of Biomedical Engineering, SUNY Stony Brook, Stony Brook, NY. “Synthetic microbial consortia.” Institute for Mathematics and its Applications Workshop: Biological Systems and Networks, Minneapolis, MN. “Synthetic microbial consortia: Engineering harmony in competing bacteria.” Seminar, Science at the Edge Series, Michigan State University, East Lansing, MI. “Using synthetic biology to understand biological rhythms.” Gordon Research Conference on Chronobiology, Girona, Spain. “Engineered temperature compensation in a synthetic genetic clock.” Texas Clock Meeting, Houston, TX. “Engineering dynamics in synthetic bacterial microconsortia.” Colloquium, Department of Bioengineering, Rice University, Houston, TX. “Engineering robustness in synthetic biology.” Seminar, Department of Biology, Trinity University, San Antonio, TX. “Robustness in synthetic gene circuits.” Winter q-Bio Conference, Waikoloa, HI. “Robustness in synthetic gene circuits.” Seminar, Department of Microbiology & Molecular Genetics, University of Texas Health Science Center, Houston, TX. “Robustness in synthetic gene circuits.” Seminar, Biophysics Graduate Program, Cornell University, Ithaca, NY. “Robustness in synthetic gene circuits.” Seminar, UT Medical School, Bacterial Interest Group (BIG), Houston, TX. “Robustness in synthetic gene circuits.” Seminar, Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL. “Synthetic development.” Seminar, Computational & Integrative Biomedical Research Center, Baylor College of Medicine, Houston, TX. “Synthetic microconsortia.” 24th Keck Center Annual Research Conference, Houston, TX. "Engineered temperature compensation in a synthetic gene oscillator.." Winter q-Bio Conference, Honolulu, HI. (February 2013) "Robustness in synthetic gene circuits." Keck Seminar, Houston, TX. (September, 2013) "The design problem in synthetic biology." Design Automation Conference, Austion, TX. (June 2013) "Engineered temperature compensation in a synthetic gene oscillator." BIG Meeting, UT Medical School, Houston, TX. (November 2012) "Engineering temperature compensation in a synthetic gene oscillator.." Nanobiology Interdisciplinary Graduate Training Program Seminar, Houston, TX. (October 2012) "Modeling the dynamics of synthetic gene networks.." Biomedical Engineering Society Annual Meeting, Atlanta, GA. (October 2012) "The origins of delay in gene network dynamics.." q-Bio Summer School in Synthetic Biology, San Diego, CA. (July 2012) "Synthetic Biology." IBB Science in the News, Rice University, Houston, TX. (June 2011) "Synthetic Biology." NSF Bionetworks Summer Research Program, Rice University, Houston, TX. (June 2011) "Synthetic gene oscillators and transcriptional delay noise." APS March Meeting, Dallas, TX. (March 2011) "Synthetic gene oscillators in bacteria." Bacterial Interest Group (BIG) Meeting, UT Medical School, Houston, TX. (March 2011) "Modeling the dynamics of a synthetic gene oscillator." Workshop on Synthetic Biology, Mathematic Biosciences Institute, Columbus, OH. (1/29/2010) "Modeling the dynamics of a synthetic gene oscillator." AAAS - SWARM (Synthetic Biology section), Houston, TX. (4/9/2010) "Modeling the dynamics of a synthetic geneoscillator." Symposium: From networks to pattern formation, Rice University, Houston, TX. (December) "Modeling the dynamics of gene regulation in single cells." Interdisciplinary Program in Networks, University of Houston, Houston, TX. (2/12/2010) "Synthetic Biology." NSF Bionetworks Summer Research Program, Rice University, Houston, TX. (7/28/2010) "The dynamics of gene regulation in single cells." AAAS - SWARM (Systems Biology session), Houston, TX. (4/8/2010) "The dynamics of synthetic gene networks." Rice Summer Institute, Houston, TX. (7/1/2010) "The role of regulated mRNA turnover in yeast diauxie." Amyris, Emeryville, CA. (3/5/2010) "Modeling the dynamics of gene regulation in single cells." Rice University, Department of Computer Science, Houston, TX. (2009) "Modeling the dynamics of gene regulatory networks: A cautionary tale.." (10/19/2009) "The dynamics of gene regulation in single cells." Rice University, Department of Biochemistry and Cell Biology, Houston, TX. (2009) "Metabolic gene regulation in a dynamically changing environment." 12th International Congress on Yeasts, Kiev, Ukraine. (2008) "Metabolic gene regulation in a dynamically changing environment." Q-Bio Conference on Cellular Information Processing, Santa Fe, NM. (2007) With W. L. Pang, N. A. Ostroff, B. L. Baumgartner, S. Nayak, L. S. Tsimring and J. Hasty Keynote Speaker “The promises and challenges of synthetic biology.” Synthetic Biology Future Conference, Cork, Ireland. "Engineered temperature compensation in a synthetic gene oscillator.." Rice Regional Undergraduate Research Symposium, Houston, TX. (October 2012) Other "Modeling the genetic dual-feedback oscillator." Q-Bio Conference on Cellular Information Processing, Santa Fe, NM . (2008) With W. Mather, L. S. Tsimring and J. Hasty Posters "Modeling the genetic dual-feedback oscillator." Q-Bio Conference on Cellular Information Processing, Santa Fe, NM . (2008) With W. Mather, L. S. Tsimring and J. Hasty Seminar Speaker "Engineered temperature compensation in a sythetic gene oscilator." Department of Bioengineering, California Institute of Technology, Pasadena, CA. (May 2013) "Engineered temperature compensation in a synthetic gene oscillator.." Department of Systems Biology, MD Anderson Cancer Center, Houston, TX. (November 2012) "Engineered temperature compensation in a synthetic gene oscillator.." Department of Biochemistry, University of Texas - Austin, Autsin, TX. (October 2012) Session Chair "Session Chair." Winter Q-Bio Conference, Honolulu, HI. (February 2013) Supervised Theses & Dissertations Truong Nguyen, PhD Understanding dynamic activities of genetic network under environmental changes. (2015) (Thesis or Dissertation Director) David Shis, Ph.D. Engineering multi-input gene regulation for applications in Synthetic Biology. (2015) (Thesis or Dissertation Director) Yu-Yu Cheng, PhD Characterization of transcriptional delay by synthetic biology approach. (2016) (Thesis or Dissertation Director) Andrew Hirning, TBD. (2016) (Thesis or Dissertation Director) Ye Chen, PhD Multi-strain synthetic biology: Design and construction of genetically controlled micro-ecosystems. (2016) (Thesis or Dissertation Director) Erin O'Brien, TBD. (2016) (Thesis or Dissertation Director) Barbara De Freitas Malgalhaes, TBD. (2019) (Thesis or Dissertation Director) Razan Alnahhas, TBD. (2019) (Thesis or Dissertation Director) Sara Molinari, TBD. (Thesis or Dissertation Director) David Zong, TBD. (Thesis or Dissertation Director) Emily E Thomas, Increasing spatiotemporal control over azidonorleucineprotein labeling within cells to enable higher resolution proteomics. (Committee Member)