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Ron Weiss

Synthetic Biology

My research focuses on programming new cellular behaviors by designing and embedding synthetic gene networks that perform desired functions in single cells and multi-cellular environments. We genetically engineer a variety of cell types including bacteria, yeast, and mammalian stem cells. This nascent field of Synthetic Biology holds promise for a wide range of applications such as programmed tissue engineering,environmental and effecting, biomaterial fabrication, and an improved understanding of naturally biological processes

The construction of de-novo genetic circuits begins with the assembly and characterization of genetic parts, or building blocks. We have assembled a library of genetic components that regulate transcription, translation, phosphorylation, and synthesis of and response to signaling molecules such as acyl-homoserine lactones in bacteria and cytokinins in Eukaryotes. We then combine these parts into various network topologies that elicit new behaviors in a programmable fashion. In single cells, we have constructed transcriptional cascades and other network topologies with feedback and feed-forward motifs. We have shown theoretically and experimentally that these networks can perform digital computation, attenuate gene expression noise, or exhibit analog programmed functions such as pulse generation. Through the construction and analysis of such fundamental network motifs, we aim to demonstrate sophisticated programmed control over gene expression as well as improve our quantitative understanding of naturally occurring complex gene networks.

Another major emphasis is engineering synthetic multicellular systems through the integration of intracellular circuits with cell-cell communication mechanisms (e.g. lux and rhl quorum sensing systems). Beginning with simple sender-receiver systems, we have built a variety of more sophisticated multicellular interactions for coordinated cell behaviors. One such system is the pulse generator where sender cells communicate to nearby receiver cells, which then respond with a transient burst of gene expression whose amplitude and duration depends on the distance from the senders. In another system, receiver cells have been engineered to respond to cell-cell communication signals from senders, but only if the signal concentrations fall within prespecified ranges. We demonstrated experimentally how a multicellular system that consists of several different detection thresholds can generate a variety of interesting spatial patterns (shown in the figures below). In a third system, cells have been engineered to “play” Conway’s Game of Life, where cells live or die based on the density of their neighbors. This system exhibits complex global emergent behavior that arises from the interaction of cells based on simple local rules. We are currently building a variety of other multicellular systems in bacteria that have interesting spatiotemporal dynamics. Finally, we are also implementing synthetic gene networks and artificial cell-cell communication in mammalian stem cells in order to control the spatiotemporal expression patterns of cell fate regulators, with novel applications in programmed tissue engineering.

Selected Publications

Lu T, Ferry M, Weiss R, Hasty J. (2008) A molecular noise generator. Phys Biol. 5: 36006. PubMed

Brenner K, Karig DK, Weiss R, Arnold FH. (2007) Engineered biodirectional communication mediates a consensus in a microbial biofilm consortium. Proc Natl Acad Sci . 104: 17300-17304. PubMed

Batt G, Yordanov B, Weiss R, Belta C. (2007) Robustness analysis and tuning of synthetic gene networks. Bioinformatics 23: 2415-2422. PubMed

Rinaudo K, Bleris L, Maddamsetti R, Subramanian S, Weiss R, Benenson Y. (2007) A universal RNAi-based logic evaluator that operates in mammalian cells. Nature Biotech 25: 795-801. PubMed

Batt G, Belta C, Weiss R. (2007) Model checking genetic regulatory networks with parameter uncertainty. 10th International Workshop on Hybrid Systems: Computation and Control . April 2007.

Batt G, Belta C, Weiss R. (2007) Model checking liveness properties of genetic regulatory networks. 13th International Conference on Tools and Algorithms for the Construction and Analysis of Systems.

Hooshangi S, Weiss R (2006). The effect of negative feedback on noise propagation in transcriptional gene networks. Chaos 16: 026108. PubMed

Andrianantoandro E, Basu S, Karig DK, Weiss R (2006). Synthetic biology: new engineering rules for an emerging discipline. Mol Syst Biol 2: 2006.0028. PubMed

Hooshangi S, Weiss R (2006). The effect of negative feedback on noise propagation in transcriptional gene networks. Chaos 16: 26108. PubMed

Andrianantoandro E, Basu S, Karig DK, Weiss R (2006). Synthetic biology: new engineering rules for an emerging discipline. Mol Syst Biol 2: 2006.0028. PubMed

McDaniel R, Weiss R (2005). Advances in synthetic biology: on the path from prototypes to applications. Curr Opin Biotechnol 16: 476-483. PubMed

Chen MT, Weiss R (2005). Artificial cell-cell communication in yeast Saccharomyces cerevisiae using signaling elements from Arabidopsis thaliana. Nat Biotechnol 23: 1551-1555. PubMed

Basu S, Gerchman Y, Collins CH, Arnold FH, Weiss R (2005). A synthetic multicellular system for programmed pattern formation. Nature 434: 1130-1134. PubMed

Karig D and Weiss R (2005). Signal-amplifying genetic circuit enables in vivo observation of weak promoter activation in the Rhl quorum sensing system. Biotechnol Bioeng 89: 709-718. PubMed

Hsu A, Vijayan V, Gerchman LF, Basu YS, et al. (2005). Dynamic control in a coordinated multi-cellular maze solving system. American Controls Conference.

Hooshangi S, Thiberge S and Weiss R (2005). Ultrasensitivity and noise propagation in a synthetic transcriptional cascade. Proc Natl Acad Sci USA 102: 3581-3586. PubMed

Chen MT and Weiss R (2005). Artificial cell-cell communication in yeast Saccharomyces cerevisiae using signaling elements from Arabidopsis thaliana. Nat Biotechnol 23: 1551-1555. PubMed

Braun, Basu S and Weiss R (2005). Parameter Estimation for two synthetic gene networks: a case study. IEEE International conference on acoustics, speech and signal processing.

Basu S, Gerchman Y, Collins CH, Arnold FH and Weiss R (2005). A synthetic multicellular system for programmed pattern formation. Nature 434: 1130-1134. PubMed

You L, Cox RS, 3rd, Weiss R and Arnold FH (2004). Programmed population control by cell-cell communication and regulated killing. Nature 428: 868-871. PubMed

Gerchman Y and Weiss R (2004). Teaching bacteria a new language. Proc Natl Acad Sci USA 101: 2221-2222. PubMed

Feng XJ, Hooshangi S, Chen D, Li G, Weiss R, Rabitz H (2004). Optimizing genetic circuits by global sensitivity analysis. Biophys J 87: 2195-2202. PubMed

Basu S, Mehreja R, Thiberge S, Chen MT and Weiss R (2004). Spatiotemporal control of gene expression with pulse-generating networks. Proc Natl Acad Sci USA 101: 6355-6360. PubMed

Weiss R (2003). Challenges and opportunities in programming living cells. The Bridge 33: 39-46.

Basu S, Karig D and Weiss R (2003). Engineering signal processing in cells: towards molecular concentration band detection. Nat Comp 2: 463-478.