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 This study built upon a smaller, earlier study led by Tom Knight (unpublished at this time).Biology is a technology for processing information, materials, and energy.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

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

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

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

Enabling community-based metrology for wood-degrading fungi

Background: Lignocellulosic biomass could support a greatly-expanded bioeconomy. Current strategies for using biomass typically rely on single-cell organisms and extensive ancillary equipment to produce precursors for downstream manufacturing processes. Alternative forms of bioproduction based on solid-state fermentation and wood-degrading fungi could enable more direct means of manufacture. However, basic methods for cultivating wood-degrading fungi are often ad hoc and not readily reproducible. Here, we developed standard reference strains, substrates, measurements, and methods sufficient to begin to enable reliable reuse of mycological materials and products in simple laboratory settings. Results: We show that a widely-available and globally-regularized consumer product (Pringles™) can support the growth of wood-degrading fungi, and that growth on Pringles™-broth can be correlated with growth on media made from a fully-traceable and compositionally characterized substrate (National Institute of Standards and Technology Reference Material 8492 Eastern Cottonwood Whole Biomass Feedstock). We also establish a Relative Extension Unit (REU) framework that is designed to reduce variation in quantification of radial growth measurements. So enabled, we demonstrate that five laboratories were able to compare measurements of wood-fungus performance via a simple radial extension growth rate assay, and that our REU-based approach reduced variation in reported measurements by up to ~ 75%. Conclusions: Reliable reuse of materials, measures, and methods is necessary to enable distributed bioproduction processes that can be adopted at all scales, from local to industrial. Our community-based measurement methods incentivize practitioners to coordinate the reuse of standard materials, methods, strains, and to share information supporting work with wood-degrading fungi