Robust Multi-Layer Control Systems for Cooperative Cellular Behaviors

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The goal of this project is to develop and demonstrate a multi-layer intra- and inter-cellular control systems integrated to create complex, spatially-organized, multi-functional model system for wound healing. Our system makes use of a layered control architecture with feedback at the DNA, RNA, protein, cellular and population levels to provide programmed phenotypic differentiation and interconnection between multiple cell types.

This project is an active collaboration with John Doyle, Michael Elowitz and Niles Pierce. This page describes the activities taking place in Richard Murray's group.

Current participants:

  • Leopold Green (Postdoc, BE)
  • Chelsea Hu (Postdoc, BE)
  • Reed McCardell (PhD student, BE)
  • Mark Prator (Technician, EAS)
  • Xinying (Cindy) Ren (PhD student, CDS)

Additional participants:

  • Samuel Clamons (PhD student, BE)
  • Andrew Halleran (PhD student, BE)
  • James Parkin (PhD student, BE)
  • Andrey Shur (PhD student, BE)

Collaborators:

  • John Doyle (Caltech CMS)
  • Michael Elowitz (Caltech BBE)
  • Niles Pierce (Caltech BBE)

Past participants:

  • Ania Baetica (Alumni, CDS)
  • Victoria Hsiao (PhD student, BE)
  • Anandh Swaminathan (Alumni, CDS)

Objectives

Darpa-biocon.png

Phase I objectives (Murray group):

  • Biological controllers: Design and implement feedback controllers in E. coli to modulate growth rate in response to an input. Inputs will consist of small molecule inducers available in environment or secreted by other cells, and outputs will be bacterial concentrations.
  • Testbeds: Develop microfluidic devices for temporal measurement and control of growth environments for bacterial systems.
  • Testbeds: Develop spatially patterned testbeds for temporal measurement and control of bacterial cell population patterning.
  • Theory: Design and simulate classes of controllers and identify those that fulfill performance objectives. Convert performance objectives into optimization constraints. Verify design robustness to perturbations in biological parts and in external environment.
  • Theory: Develop predictive models for cooperative, multi-cellular systems for preliminary analysis and design of local input/output dynamics and interconnection structure.

References



The project or effort depicted was or is sponsored by the Defense Advanced Research Projects Agency (Agreement HR0011-17-2-0008). The content of the information does not necessarily reflect the position or the policy of the Government, and no official endorsement should be inferred.

  • Agency: DARPA
  • Grant number: HR0011-17-2-0008
  • Start date: 19 Oct 2016
  • End date: 18 Oct 2020
  • Support: 1-2 postdocs, 3 graduate students, 1 FTE technician
  • Reporting: Monthly updates + quarterly reports