http://hdl.handle.net/1721.1/18185 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/1721.1/41842 pCH1497-ASD1 Canton, Bartholomew This plasmid was a kind gift from Christopher Hayes, UCSB. Fri, 23 May 2008 17:07:37 GMT http://hdl.handle.net/1721.1/41841 Software files to support thesis of Ty Thomson Thomson, Ty Wed, 21 May 2008 19:36:14 GMT