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Showing papers by "Ron Weiss published in 2003"


Journal ArticleDOI
TL;DR: An emerging engineering discipline to program cell behaviors by embedding synthetic gene networks that perform computation, communications, and signal processing and employs directed evolution to optimize genetic circuitbehavior.
Abstract: In this paper, we review an emerging engineering discipline to program cell behaviors by embedding synthetic gene networks that perform computation, communications, and signal processing. To accomplish this goal, we begin with a genetic component library and a biocircuit design methodology for assembling these components into compound circuits. The main challenge in biocircuit design lies in selecting well-matched genetic components that when coupled, reliably produce the desired behavior. We use simulation tools to guide circuit design, a process that consists of selecting the appropriate components and genetically modifying existing components until the desired behavior is achieved. In addition to such rational design, we also employ directed evolution to optimize genetic circuit behavior. Building on Nature's fundamental principle of evolution, this unique process directs cells to mutate their own DNA until they find gene network configurations that exhibit the desired system characteristics. The integration of all the above capabilities in future synthetic gene networks will enable cells to perform sophisticated digital and analog computation, both as individual entities and as part of larger cell communities. This engineering discipline and its associated tools will advance the capabilities of genetic engineering, and allow us to harness cells for a myriad of applications not previously achievable.

224 citations


Journal ArticleDOI
TL;DR: This work proposes the use of laboratory evolution methods to create new circuit components and optimize circuit performance inside living cells to gain insight into how natural genetic networks function with remarkable robustness, stability, and adaptability to changing environments.
Abstract: Synthetic genetic circuits are artificial networks of transcriptional control elements inserted into living cells in order to ‘program’ cellular behavior. We can extend this application to programming population behavior by incorporating cell-cell communications capabilities. By designing and building such networks, cellular circuit engineers expect to gain insight into how natural genetic networks function with remarkable robustness, stability, and adaptability to changing environments. Programmed cells also have promising applications in biotechnology and medicine. A major challenge that biological circuit engineers face is the difficulty of predicting circuit performance at the design stage, with the consequence that actual construction requires significant experimental effort, even for very simple circuits. To address this fundamental obstacle we propose the use of laboratory evolution methods to create new circuit components and optimize circuit performance inside living cells.

42 citations


Journal ArticleDOI
TL;DR: A new genetic signal processing circuit that can be configured to detect various chemical concentration ranges of ligand molecules and adjust the concentration band thresholds by altering the kinetic properties of specific genetic elements, such as ribosome binding site efficiencies or dna-binding protein affinities to their operators.
Abstract: We seek to couple protein-ligand interactions with synthetic gene networks in order to equip cells with the ability to process internal and environmental information in novel ways. In this paper, we propose and analyze a new genetic signal processing circuit that can be configured to detect various chemical concentration ranges of ligand molecules. These molecules freely diffuse from the environment into the cell. The circuit detects acyl-homoserine lactone ligand molecules, determines if the molecular concentration falls within two prespecified thresholds, and reports the outcome with a fluorescent protein. In the analysis of the circuit and the description of preliminary experimental results, we demonstrate how to adjust the concentration band thresholds by altering the kinetic properties of specific genetic elements, such as ribosome binding site efficiencies or dna-binding protein affinities to their operators.

22 citations