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Quorum Sensing Circuitry - Engineering Biological Signaling for Superior Cell Function

Quorum Sensing Circuitry - Engineering Biological Signaling for Superior Cell Function. William E. Bentley Robert E. Fischell Distinguished Professor & Chair Fischell Department of Bioengineering, Department of Chemical and Biomolecular Engineering,

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Quorum Sensing Circuitry - Engineering Biological Signaling for Superior Cell Function

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  1. Quorum Sensing Circuitry - Engineering Biological Signaling for Superior Cell Function William E. Bentley Robert E. Fischell Distinguished Professor & Chair Fischell Department of Bioengineering, Department of Chemical and Biomolecular Engineering, and Institute for Bioscience and Biotechnology Research University of Maryland, College Park

  2. What does bacterial cell-cell signaling do? Myxococcus enables “talk” Paenibacillus vortex S. aureus

  3. Intracellular signaling AI-2 disease intercellular signaling AI-1 Intracellular signaling Intracellular signaling Motivation: E. coli (EHEC) S. aureus P. aeruginosa (cystic fibrosis)

  4. Can learn from nature and “tune” biological systems? Did you fix the sink yet?

  5. Alternative motivations – synthetic biology

  6. Mechanisms of quorum machinery in E. coli … LsrR LsrC ATP LsrA LsrK LsrB ADP P LsrD LsrA P lsrK lsrR lsrA lsrC lsrD lsrB lsrF lsrG - + CRP - s - cAMP Glucose or PTS sugars - luxS pfs LuxS pfs E. coli AI-2 SRH SAH Wang et al., J. Bact., 187:2066-76, 2005. Wang et al., J. Bact., 187:8350-60, 2005. Gonzalez-Barrios, J. Bact., 188:305-316, 2006 Li et al., J. Bact., 189:6011-6020, 2007

  7. Current Efforts - WEB Biology has extraordinary ability to sense and interpret cues, and take action – at length scales far smaller than man-made machines. Moreover, these cues can vary from small molecules to nearest neighbors and can include physical states. Bacterial “quorum sensing” (QS) provides a rich “tapestry” for understanding biological signal transduction. QS also provides both a conceptual and physical platform for creating a next generation sensor/actuator systems – both within cells and within devices. Our goal is to understand the system, abstract its features, and develop (1) cells that behave in controlled ways in a directed, but autonomous manner and (2) a device that enables two-way (biological ↔ abiological) communication and actuation.

  8. Two demonstrations: 1. autonomous protein production 2. guiding “social” interactions “Plug & Play” Cassette T7pol

  9. Thanks for your attention!! Questions? Thanks to our sponsors: NSF, DTRA, EPA, ONR, & RW Deutsch Foundation

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