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      <page pageid="144" ns="0" title="Robust multicellular computing using genetically-encoded NOR gates and chemical “wires”">
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          <rev xml:space="preserve">Computation underlies the organization of cells into higher-order structures; for example, during development or the spatial association of bacteria in a biofilm. Often, each cell performs a simple computational operation, but when combined with cell-cell communication, intricate patterns are produced. Here, we study this process by combining a simple genetic circuit with quorum sensing in order to produce more complex computations in space. A simple NOR gate is constructed by arranging two tandem promoters to serve as inputs to drive the transcription of a repressor.  The repressor inactivates a promoter that serves as the output.  Individual colonies of E. coli carry the same NOR gate, but the inputs and outputs are wired to different orthogonal quorum sensing “sender” and “receiver” devices. This forms the wires between gates. By arranging the colonies in different spatial configurations, all possible 2-input gates are produced, including the difficult XOR and EQUALS functions. This work helps elucidate the design rules by which simple logic can be harnessed to produce more complex calculations by rewiring communication between cells</rev>
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      <page pageid="152" ns="0" title="Robustness in Nature: Challenges and Opportunities for the Systems Biology Community">
        <revisions>
          <rev xml:space="preserve">Robustness, the ability to maintain performance in the face of perturbations and uncertainty, is a key property of living systems. While ‘homeostasis’ has long been recognized as an important phenomenon, the molecular and cellular bases of robustness have only recently begun to be understood. Biology and engineering employ a common set of basic ‘control’ mechanisms to achieve such robust regulation, namely redundancy, feedback control, modularity and hierarchies to ensure robust performance. New systems theoretical approaches to complex engineered systems are required that allow the reverse engineering of general design principles that can provide insights into cellular robustness. While preliminary results are available for simple (low-dimensional, deterministic) biological systems, general tools for analyzing these trade-offs are the subject of active research.

In this talk, I will outline methods that are drawn from the field of control and dynamic systems to generate insights into the functioning of these robust biophysical networks. Examples will be used to motivate problems and methodologies, including two from the medical field (Alzheimer’s Disease, Post-traumatic Stress Disorder) and one from Ecology (Synchronization in Annual Spawning of Coral).</rev>
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