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2004 World Technology Awards Winners & Finalists
Please describe the work that you are doing that you consider to be the most innovative and of the greatest likely long-term significance.
With recent advances in our understanding of cellular processes and DNA synthesis methods, we can now regard cells as “programmable matter.” Through genetic engineering, we are equipping cells with new sophisticated capabilities for gene regulation, information processing, and communication. These new capabilities serve as catalysts for Synthetic Biology, an emerging engineering discipline to program cell behaviors as easily as we program computers. Synthetic biology will benefit a wide variety of existing fields and enable us to harness cells for applications that are not feasible today. Applications include tissue engineering, molecular fabrication of biomaterials and nanostructures, synthesis of pharmaceutical products, biosensing, and improved quantitative insights into the operating principles that govern living organisms.
A major focus of my research is to create an infrastructure for synthetic biology applications by constructing prototype gene networks that perform digital computation, analog signal processing, and cell-cell communications. We have demonstrated experimentally how in vivo biochemical reactions such as transcription and translation can be configured to perform digital logic operations (e.g. NOT, AND, and IMPLIES) both in bacteria and in mammalian cells. Theoretically, any arbitrary digital logic function can be implemented with genetic circuits using these operations. We have recently demonstrated the feasibility of implementing complex digital logic circuits by showing that transcriptional cascades with appropriately matched genetic components exhibit improved digital behavior in comparison to the behavior of the individual elements.
We have also engineered synthetic gene networks with desired analog and transient behaviors. For example, the pulse generator network transiently expresses a gene of interest in response to a long-lasting signal from neighboring cells. Similar transient responses are common in a variety of biological processes including embryogenesis and immune responses. The signal amplifying gene network is able to detect very small changes in transcriptional activity in response to cell-cell communication. With this network we discovered bacterial quorum sensing behavior that was previously undetected. The signal amplification network could also be used for medical diagnostic and biosensing applications to detect trace amounts of toxins, pathogens, or disease markers that cannot be detected through direct observation.
Extraordinary richness in biology is due to cell-cell communication where simple rules governing local interactions between cells often yield complex global behavior. In order to explore such emergent behavior, we genetically engineered bacteria to “play” Conway’s famous Game of Life, a classic computer simulation of population dynamics. As with the computer version, cells are engineered to die due to overpopulation or when they have too few neighbors. While the bacterial system exhibited the same general behavior as the computer simulations, microscopy analysis of the system revealed non-deterministic behavior due to noise in gene expression and chemical diffusion. The analysis of such artificial systems can help improve our understanding of the rules that govern the complex global behavior of real living systems.
Using engineered cell-cell communication, we have also recently programmed cells to form desired spatiotemporal patterns. One example is a bullseye pattern, where an initial homogeneous population of engineered receiver cells differentiates into rings that fluoresce in different colors based on the distance of the receiver cells from deliberately placed sender cells. The capability to direct cells to form patterns on demand will have a variety of applications with perhaps the greatest impact in tissue engineering. We have built synthetic gene networks that turn on “master switches” in stem cells at precise times and under well controlled and well defined conditions. We anticipate that this work will ultimately allow us to engineer stem cell differentiation patterns on demand and provide us with previously unattainable capabilities to repair damaged tissues, heal wounds, and regenerate organs.
Ron Weiss is an Assistant Professor of Electrical Engineering at Princeton University, and is also associated with the Department of Molecular Biology. He received his PhD from the Massachusetts Institute of Technology in Computer Science and Electrical Engineering (2001). His research focuses primarily on Synthetic Biology, where he programs cell behavior by constructing and modeling biochemical and cellular computing systems. A major thrust of his work is the synthesis of gene networks that are engineered to perform in vivo analog and digital logic computation. He is also interested in programming cell aggregates to perform coordinated tasks using cell-cell communication with chemical diffusion mechanisms such as quorum sensing. He has constructed and tested several novel in-vivo biochemical logic circuits and intercellular communication systems. Weiss is interested in both hands-on experimental work and in implementing software infrastructures for simulation and design work. He has written numerous research articles, given talks to a wide variety of audiences, and served in government panels. For his work in Synthetic Biology, Weiss has received MIT's Technology Review Magazine's TR100 Award ("top 100 young innovators", 2003), was selected as a speaker for the National Academy of Engineering's Frontiers of Engineering Symposium (2003), received the E. Lawrence Keyes, Jr./Emerson Electric Company Faculty Advancement Award at Princeton University (2003), and his research in Synthetic Biology was named by MIT's Technology Review Magazine as one of "10 emerging technologies that will change your world" (2004).
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