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      Eugene – A Domain Specific Language for Specifying and Constraining Synthetic Biological Parts, Devices, and Systems

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          Abstract

          Background

          Synthetic biological systems are currently created by an ad-hoc, iterative process of specification, design, and assembly. These systems would greatly benefit from a more formalized and rigorous specification of the desired system components as well as constraints on their composition. Therefore, the creation of robust and efficient design flows and tools is imperative. We present a human readable language (Eugene) that allows for the specification of synthetic biological designs based on biological parts, as well as provides a very expressive constraint system to drive the automatic creation of composite Parts (Devices) from a collection of individual Parts.

          Results

          We illustrate Eugene's capabilities in three different areas: Device specification, design space exploration, and assembly and simulation integration. These results highlight Eugene's ability to create combinatorial design spaces and prune these spaces for simulation or physical assembly. Eugene creates functional designs quickly and cost-effectively.

          Conclusions

          Eugene is intended for forward engineering of DNA-based devices, and through its data types and execution semantics, reflects the desired abstraction hierarchy in synthetic biology. Eugene provides a powerful constraint system which can be used to drive the creation of new devices at runtime. It accomplishes all of this while being part of a larger tool chain which includes support for design, simulation, and physical device assembly.

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          Most cited references38

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          Foundations for engineering biology.

          Drew Endy (2005)
          Engineered biological systems have been used to manipulate information, construct materials, process chemicals, produce energy, provide food, and help maintain or enhance human health and our environment. Unfortunately, our ability to quickly and reliably engineer biological systems that behave as expected remains quite limited. Foundational technologies that make routine the engineering of biology are needed. Vibrant, open research communities and strategic leadership are necessary to ensure that the development and application of biological technologies remains overwhelmingly constructive.
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            The second wave of synthetic biology: from modules to systems.

            Synthetic biology is a research field that combines the investigative nature of biology with the constructive nature of engineering. Efforts in synthetic biology have largely focused on the creation and perfection of genetic devices and small modules that are constructed from these devices. But to view cells as true 'programmable' entities, it is now essential to develop effective strategies for assembling devices and modules into intricate, customizable larger scale systems. The ability to create such systems will result in innovative approaches to a wide range of applications, such as bioremediation, sustainable energy production and biomedical therapies.
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              Refinement and standardization of synthetic biological parts and devices.

              The ability to quickly and reliably engineer many-component systems from libraries of standard interchangeable parts is one hallmark of modern technologies. Whether the apparent complexity of living systems will permit biological engineers to develop similar capabilities is a pressing research question. We propose to adapt existing frameworks for describing engineered devices to biological objects in order to (i) direct the refinement and use of biological 'parts' and 'devices', (ii) support research on enabling reliable composition of standard biological parts and (iii) facilitate the development of abstraction hierarchies that simplify biological engineering. We use the resulting framework to describe one engineered biological device, a genetically encoded cell-cell communication receiver named BBa_F2620. The description of the receiver is summarized via a 'datasheet' similar to those widely used in engineering. The process of refinement and characterization leading to the BBa_F2620 datasheet may serve as a starting template for producing many standardized genetically encoded objects.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2011
                29 April 2011
                : 6
                : 4
                : e18882
                Affiliations
                [1 ]Department of Computer Science, California State Polytechnic University, Pomona, California, United States of America
                [2 ]Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, California, United States of America
                [3 ]Department of Bioengineering, University of California San Diego, La Jolla, California, United States of America
                [4 ]Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, Minnesota, United States of America
                [5 ]Department of Bioengineering, QB3: California Institute for Quantitative Biological Research, University of California, Berkeley, California, United States of America
                [6 ]Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America
                [7 ]Department of Electrical and Computer Engineering, Boston University, Boston, Massachusetts, United States of America
                Fondazione Telethon, Italy
                Author notes

                Conceived and designed the experiments: LB AL SC BX ML EW JCA DMD. Performed the experiments: LB AL SC BX EW ML. Analyzed the data: LB SC EW ML. Contributed reagents/materials/analysis tools: JCA DMD. Wrote the paper: LB AL SC EW BX DMD.

                Article
                10-PONE-RA-18910
                10.1371/journal.pone.0018882
                3084710
                21559524
                05cfff1e-0da9-47f3-a50c-1ff4769858ea
                Bilitchenko et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 31 August 2010
                : 24 March 2011
                Page count
                Pages: 12
                Categories
                Research Article
                Biology
                Synthetic Biology

                Uncategorized
                Uncategorized

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