http://hdl.handle.net/1721.1/18186 http://hdl.handle.net/1721.1/41867 MONOD, a Collaborative Tool for Manipulating Biological Knowledge Soergel, David Choi, Kirindi Thomson, Ty Doane, Jay George, Brian Morgan-Linial, Ross Brent, Roger Endy, Drew We describe an open source software tool called MONOD, for Modeler’s Notebook and Datastore, designed to capture and communicate knowledge generated during the process of building models of many-component biological systems. We used MONOD to construct a model of the pheromone response signaling pathway of Saccharomyces cerevisiae. MONOD allowed the accumulation, documentation, and exchange of data, valuations, assumptions, and decisions generated during the model building process. MONOD thus helped preserve a record of the steps taken on the path between from the experimental data to the computable model. We believe that MONOD and its successors may streamline the processes of building models, communicating with other researchers, and managing and manipulating biological knowledge. "Collaborative annotation"-- fine-grained, structured, searchable communication enabled by software tools of this type-- could positively affect the practice of biological research. Research article written in 2004 describing MONOD, an early biological knowledge management system Thu, 19 Jun 2008 13:10:14 GMT http://hdl.handle.net/1721.1/41843 Applying engineering principles to the design and construction of transcriptional devices Shetty, Reshma P The aim of this thesis is to consider how fundamental engineering principles might best be applied to the design and construction of engineered biological systems. I begin by applying these principles to a key application area of synthetic biology: metabolic engineering. Abstraction is used to compile a desired system function, reprogramming bacterial odor, to devices with human-defined function, then to biological parts, and finally to genetic sequences. Standardization is used to make the process of engineering a multi-component system easier. I then focus on devices that implement digital information processing through transcriptional regulation in Escherichia coli. For simplicity, I limit the discussion to a particular type of device, a trancriptional inverter, although much of the work applies to other devices as well. First, I discuss basic issues in transcriptional inverter design. Identification of key metrics for evaluating the quality of a static device behavior allows informed device design that optimizes digital performance. Second, I address the issue of ensuring that transcriptional devices work in combination by presenting a framework for developing standards for functional composition. The framework relies on additional measures of device performance, such as error rate and the operational demand the device places on the cellular chassis, in order to proscribe standard device signal thresholds. Third, I develop an experimental, proof-of-principle implementation of a transcriptional inverter based on a synthetic transcription factor derived from a zinc finger DNA binding domain and a leucine zipper dimerization domain. Zinc fingers and leucine zippers offer a potential scalable solution to the challenge of building libraries of transcription-based logic devices for arbitrary information processing in cells. Finally, I extend the principle of physical composition standards from parts and devices to the vectors that propagate those parts and devices. The new vectors support the assembly of biological systems. Taken together, the work helps to advance the transformation of biological system design from an ad hoc, artisanal craft to a more predictable, engineering discipline. Ph.D. thesis (user submitted) Tue, 27 May 2008 20:53:42 GMT http://hdl.handle.net/1721.1/40280 A Practical Perspective on DNA Synthesis and Biological Security (12/4/2006 Draft) Bügl, Hans Danner, John Molinari, Robert Mulligan, John Roth, David Wagner, Ralf Budowle, Bruce Scripp, Robert Smith, Jenifer Steele, Scott Church, George Endy, Drew Few developments have leapfrogged over predecessor technology as quickly and extensively as synthetic biology. Based on cutting-edge DNA synthesis technology, synthetic biology has already fueled an expansion of opportunities in biological engineering, with advanced capabilities that surpass those provided by traditional recombinant DNA technology. Improvements in synthesis technology are accelerating the pace of innovation in everything from the development of renewable energy to the production of bulk and fine chemicals, from information processing to environmental monitoring, and from agricultural productivity to breakthroughs in human health and medicine. Synthetic biology promises vast improvements to our well-being and our understanding of the living world. Like any powerful technology, DNA synthesis has the potential to be misused. In the wrong hands, the new capabilities enabled by synthetic biology could give rise to both known and unforeseeable threats to our biological safety and security. Current government oversight of the DNA synthesis industry falls short of addressing this unfortunate reality. Here, we introduce and outline a practical plan for developing an effective governance framework for the DNA synthesis industry. A thoughtfully crafted and effectively implemented framework would protect our continued well-being in at least two ways. First, the framework would promote our biological safety and security. Second, the framework would encourage the further responsible development of synthetic biology technologies and their continued, overwhelmingly constructive application. The proposed plan represents the collective views of the International Consortium for Polynucleotide Synthesis, the U.S. Federal Bureau of Investigation, the Chief Executive Officers or Presidents of several of the principal synthetic biology companies, and representatives from academia. Our framework calls for the immediate and systematic implementation of a tiered DNA synthesis screening process. In order to establish accountability at the user level, individuals who place orders for DNA synthesis would be required to identify themselves, their home organization, and all relevant biosafety level information. Next, individual companies would use software tools to check synthesis orders against a set of select agents or sequences to help ensure regulatory compliance and flag synthesis orders for further review. Finally, DNA synthesis and synthetic biology companies would work together, and interface with appropriate government agencies, to rapidly and continually improve the underlying technologies used to screen orders and identify potentially dangerous sequences, as well as develop a clearly defined process to report behavior that falls outside of agreed-upon guidelines. This is the unabridged draft of the manuscript "DNA synthesis and biological security." An abridged form of this manuscript was later published as a peer review commentary in Nature Biotechnology (doi:10.1038/nbt0607-627) Tue, 12 Dec 2006 20:16:41 GMT http://hdl.handle.net/1721.1/39658 Working Papers for Synthetic Genomics: Risks and Benefits for Science and Society Garfinkel, Michele Endy, Drew Epstein, Gerald Friedman, Robert The following papers were commissioned for the project Synthetic Genomics: Risks and Benefits for Science and Society. These papers formed the basis of many discussions at project workshops and at a large invitational meeting. The information elicited from these meetings, and from the commissioned papers themselves, formed the basis of our report Synthetic Genomics: Options for Governance (http://dspace.mit.edu/handle/1721.1/39141). The views and opinions expressed in these commissioned papers are those of the authors of the papers and not necessarily those of the authors of the report, or of the institutions at which the authors work. Citation: Working Papers for Synthetic Genomics: Risks and Benefits for Science and Society. Garfinkel MS, Endy D, Epstein GL, Friedman RM, editors. 2007. Compilation of Technical Reports in Support of Sloan Foundation study on DNA synthesis and governance options Tue, 04 Dec 2007 17:33:37 GMT