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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(More)
n molecular, cellular and developmental biology, compact and elegant theories of the sort familiar in physics are rare; rather, explanations of phenomena are typically couched in natural language narratives that describe the interactions of large numbers of distinct molecular entities. In this essay, we define model as any representation of a system. Models(More)
Here we studied the quantitative behaviour and cell-to-cell variability of a prototypical eukaryotic cell-fate decision system, the mating pheromone response pathway in yeast. We dissected and measured sources of variation in system output, analysing thousands of individual, genetically identical cells. Only a small proportion of total cell-to-cell(More)
An inability to reliably predict quantitative behaviors for novel combinations of genetic elements limits the rational engineering of biological systems. We developed an expression cassette architecture for genetic elements controlling transcription and translation initiation in Escherichia coli: transcription elements encode a common mRNA start, and(More)
BACKGROUND The engineering of many-component, synthetic biological systems is being made easier by the development of collections of reusable, standard biological parts. However, the complexity of biology makes it difficult to predict the extent to which such efforts will succeed. As a first practical example, the Registry of Standard Biological Parts(More)
Bacteriophage lambda infection of Escherichia coli can result in distinct cell fate outcomes. For example, some cells lyse whereas others survive as lysogens. A quantitative biophysical model of lambda infection supports the hypothesis that spontaneous differences in the timing of individual molecular events during lambda infection leads to variation in the(More)
The practice of engineering biology now depends on the ad hoc reuse of genetic elements whose precise activities vary across changing contexts. Methods are lacking for researchers to affordably coordinate the quantification and analysis of part performance across varied environments, as needed to identify, evaluate and improve problematic part types. We(More)
The views and opinions expressed in this report are those of the authors and not necessarily those of the other study Core Group members, the participants of the workshops discussed in this report, or of the institutions at which the authors work. The authors assume full responsibility for the report and the accuracy of its contents. We gratefully(More)
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.(More)
Natural biological systems are selected by evolution to continue to exist and evolve. Evolution likely gives rise to complicated systems that are difficult to understand and manipulate. Here, we redesign the genome of a natural biological system, bacteriophage T7, in order to specify an engineered surrogate that, if viable, would be easier to study and(More)