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Synthetic biology: from bacteria to stem cells
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Short Description: Synthetic biology, genetic engineering. 1. INTRODUCTION. With recent advances in our understanding of cellular pro-. cesses and DNA synthesis methods, ...
Content Inside: 36.1 Synthetic biology: from bacteria to stem cells Ron Weiss Departments of Electrical Engineering and Molecular Biology Olden Street E-Quad B-312 Princeton University Princeton, New Jersey 08544 rweiss@princeton.edu ABSTRACT Biology, an emerging engineering discipline to program cell behaviors as easily as we program computers. Synthetic Synthetic biology is revolutionizing how we conceptualize biology will improve our quantitative understanding of nat- and approach the engineering of biological systems. Recent ural biological processes and will also have biotechnology advances in the field are allowing us to expand beyond the applications in areas such as biosensing, synthesis of phar- construction and analysis of small gene networks towards maceutical products, molecular fabrication of biomaterials the implementation of complex multicellular systems with and nanostructures, and tissue engineering. a variety of applications. We have developed an integrated We implemented genetic circuits with finely-tuned digi- computational/experimental approach to engineering com- tal and analog behavior and used artificial cell-cell commu- plex behavior in living systems ranging from bacteria to nication to coordinate the behavior of cell populations for stem cells. In our research, we appropriate useful design programmed pattern formation [1, 2, 3, 4]. In our research, principles from electrical engineering and other well estab- we use computer engineering principles of abstraction, com- lished fields. These principles include abstraction, standard- position, and interface specifications to build programmable ization, modularity, and computer aided design. But we organisms with sensors and actuators precisely controlled also spend considerable effort towards understanding what by analog and digital logic circuitry [5]. Here, recombinant makes synthetic biology different from all other existing en- DNA-binding proteins represent signals, and recombinant gineering disciplines and discovering new design and con- genes perform the computation by regulating protein expres- struction rules that are effective for this unique discipline. sion. We have built synthetic gene networks that implement biochemical logic circuits in a variety of cell types includ- Categories and Subject Descriptors ing Escherichia coli, Saccharomyces cerevisiae (yeast), and C.1.3 [Computer Systems Organizations]: Processor mammalian stem cells. These circuits incorporate a variety Architectures Other Architecture Styles of digital and analog devices including the AND, NOT, and IMPLIES logic gates and analog signal amplifiers. We have General Terms used both rational design [1] and directed evolution [6] for the construction of complex but reliable biochemical logic Experimentation circuits. Through the construction of transcriptional cascades, we Keywords studied how information flows through regulatory networks in single cells by examining noise propagation, ultrasensi- Synthetic biology, genetic engineering tivity, and impedance matching [2]. Understanding these issues is critical for the analysis and de novo engineering of 1. INTRODUCTION complex gene networks. We also constructed several syn- With recent advances in our understanding of cellular pro- thetic multicellular systems that have been programmed to cesses and DNA synthesis methods, we can now regard cells exhibit unique coordinated cell behavior. The first of these as "programmable matter." Through genetic engineering, systems is the pulse generator where sender cells commu- we are equipping cells with new sophisticated capabilities nicate to nearby receiver cells, which then respond with a for gene regulation, information processing, and communica- transient burst of gene expression whose amplitude and du- tion. These new capabilities serve as catalysts for Synthetic ration depends on the distance from the senders [3]. In the second system, receiver cells have been engineered to respond to cell-cell communication signals only within pre- Permission to make digital or hard copies of all or part of this work for specified ranges [4]. This system has been used to generate Permission personal or to make digital classroom use or is hard copies granted of without all fee or part pro of vided this that work copies for are a variety of interesting spatial patterns. In the third sys- personal not or made classroom or distrib use uted is for granted profit or without fee commercial pro adv vided antage that and copies that are copies tem, cells have been engineered to play "Conway's Game of not made bear this or distrib notice uted and the for full profit or citation commercial on the first advantage page. To and copy that copies otherwise, or Life", where cells live or die based on the density of their bear this notice republish, to and post the on full serv citation ers or to on the redistrib first ute page. to lists, To copy requires otherwise, prior to specific neighbors. This system exhibits complex global emergent republish, to permission post on and/or a serv fee. ers or to redistribute to lists, requires prior specific behavior that arises from the interaction of cells based on permission DAC 2007,and/or June a fee. 48, 2007, San Diego, California, USA. WOODST Cop OCK yright '97 2007 A El CM Paso, Texas USA 978-1-59593-627-1/07/0006 ...$5.00. simple local rules. Copyright 200X ACM X-XXXXX-XX-X/XX/XX ...$5.00. 634
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