2003 Synthetic Biology study

This is the final report of the 2002-2003 synthetic biology study, which brought together ~50 researchers to discuss an improved framework for engineering biology. The report itself takes the form of an annotated presentation and was written for a general technical audience. This study built upon a smaller, earlier study led by Tom Knight (unpublished at this time).Biology is a technology for processing information, materials, and energy. As a technology platform, biological systems provide access to artifacts and processes across a range of scales (e.g., the ribosome is a programmable nanoassembler, a bamboo shoot can grow 12” per day). Biology also forms the basis for human welfare (e.g., modest amounts of memory and logic, implemented as genetically encoded systems,would directly impact biological research and medicine). However, our ability to deploy biology as a technology and to interact intentionally with the living world is now limited; the charge to our study was to begin to specify enabling technologies that, if developed, would provide a general foundation for the engineering of biology and make routine the creation of synthetic biological systems that behave as predicted.N/

Strategy for Biological Risk & Security

Why do biological risks exist? Can we develop and implement a strategy for thoughtfully approaching future biological risks? This short, working report provides an abstract introduction to the problem of biological risk and outlines how technical and societal approaches should be combined in order to best address the challenge

Should We Synthesize A Human Genome?

Given that human genome synthesis is a technology that could be used to completely redefine the core of what now joins all of humanity together as a species, we argue that discussions of making such capacities real, like today's meeting at Harvard, should not take place without open and advance consideration of whether and under what circumstances it is morally right to proceed

The Imperative of Synthetic Biology: A Proposed National Research Initiative

A 2.5 page report outlining why the United States should launch a strategic national research initiative in synthetic biolog

A Standard Parts List for Biological Circuitry

One of the hallmarks of biochemical circuits found in nature is analog, asymmetric, asynchronous design. That is, there is little standardization of parts, e.g. all the promoters have different strengths and kinetics, transcription factors are designed to have different effects at different loci, and each enzymatic reaction has its own idiosyncratic mechanism and rates. In addition, all of the heterogeneous circuit elements are executing their functions concurrently and asynchronously. Biological circuits are seemingly designed to deal with the fluctuating delays, different time-scales and energy requirements associated with each component process of the overall network. These factors also make design of novel biochemical circuitry from existent parts difficult to achieve. Without standardization, the qualitative design methods used in other engineering fields are simply inapplicable. The de facto design methodology for biological circuitry is natural selection. Rational design of biological systems by humans has remained restricted to rather small or hit-or-miss efforts and has often relied on the ability to "select" for biochemical parts that fulfill some criteria. In practice however biological-designers are rare, and solutions are usually realized through an expensive stepwise trial and error approach or through mutation and selection. Furthermore, these otherwise practical approaches are limited in terms of the problems they can solve. We believe that implementation of designed biological circuitry is limited by issues of practice

Integrases, Aliens, & Bill Joy

synthetic biology, engineering genetic data storage, logic, and communication systems using phage and integrasesResearch presentation on recent and unpublished work before the MIT Synthetic Biology Working Group on 24 September 2012 in MIT Building 56

GeneJax: A Prototype CAD tool in support of Genome Refactoring

Refactoring is a technique used by computer scientists for improving program design. The Endy Laboratory has adapted this process to make the genomes of biological organisms more amenable to human understanding and design goals. To assist in this endeavor, we implemented GeneJax, a prototype JavaScript web application for the dissection and visualization stages of the genome refactoring process. This paper reviews key genome refactoring concepts and then discusses the features, development history, user-interface, and underlying implementation issues faced during the making of GeneJax. In addition, we provide recommendations for future GeneJax development. This paper may be of interest to engineers of CAD tools for synthetic biology

Design and Evolution of Engineered Biological Systems

Poster presented at the 2005 ICSB meeting, held at Harvard Medical School in Boston, MA.To date, engineered biological systems have been constructed via a variety of ad hoc approaches. The resulting systems should be thought of as pieces of art. We are interested in exploring how existing forward engineering approaches might be combined with directed evolution to make routine the construction of engineered biological systems. We have specified a procedure for construction of biological systems via screening of subcomponent libraries and rational re-assembly. We have begun development of tools to enable this approach, including a FACS-based screening system to rapidly measure the input/output function of a genetic circuit. Additionally, we have designed a microfluidic system that enables more sophisticated screening and selection functions. Specifically, a microfluidic chemostat integrated with a cell sorter (i.e., a sortostat). This microscope-based system will enable us to evaluate whether or not more complicated screens and selections will be of practical use in service of evolving engineered biological systems

TABASCO: A single molecule, base-pair resolved gene expression simulator

BACKGROUND: Experimental studies of gene expression have identified some of the individual molecular components and elementary reactions that comprise and control cellular behavior. Given our current understanding of gene expression, and the goals of biotechnology research, both scientists and engineers would benefit from detailed simulators that can explicitly compute genome-wide expression levels as a function of individual molecular events, including the activities and interactions of molecules on DNA at single base pair resolution. However, for practical reasons including computational tractability, available simulators have not been able to represent genome-scale models of gene expression at this level of detail. RESULTS: Here we develop a simulator, TABASCO , which enables the precise representation of individual molecules and events in gene expression for genome-scale systems. We use a single molecule computational engine to track individual molecules interacting with and along nucleic acid polymers at single base resolution. Tabasco uses logical rules to automatically update and delimit the set of species and reactions that comprise a system during simulation, thereby avoiding the need for a priori specification of all possible combinations of molecules and reaction events. We confirm that single molecule, base-pair resolved simulation using TABASCO (Tabasco) can accurately compute gene expression dynamics and, moving beyond previous simulators, provide for the direct representation of intermolecular events such as polymerase collisions and promoter occlusion. We demonstrate the computational capacity of Tabasco by simulating the entirety of gene expression during bacteriophage T7 infection; for reference, the 39,937 base pair T7 genome encodes 56 genes that are transcribed by two types of RNA polymerases active across 22 promoters. CONCLUSION: Tabasco enables genome-scale simulation of transcription and translation at individual molecule and single base-pair resolution. By directly representing the position and activity of individual molecules on DNA, Tabasco can directly test the effects of detailed molecular processes on system-wide gene expression. Tabasco would also be useful for studying the complex regulatory mechanisms controlling eukaryotic gene expression. The computational engine underlying Tabasco could also be adapted to represent other types of processive systems in which individual reaction events are organized across a single spatial dimension (e.g., polysaccharide synthesis)