Robust Multi-Layer Control Systems for Cooperative Cellular Behaviors
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.
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.
- Design Guidelines For Sequestration Feedback Networks (Ania-Ariadna Baetica, Yoke Peng Leong, Noah Olsman, Richard M. Murray, Submitted, Cell Systems (Nov 2018))</li>
- Hard Limits And Performance Tradeoffs In A Class Of Sequestration Feedback Systems (Noah Olsman, Ania-Ariadna Baetica, Fangzhou Xiao, Yoke Peng Leong, John Doyle, Richard Murray, Submitted, Cell Systems (Nov 2018))
- Model of Paradoxical Signaling Regulated T-Cell Population Control for Design of Synthetic Circuits (Michaelle N. Mayalu, Harman Mehta and Richard M. Murray, Submitted, 2019 European Control Conference (ECC))
- Cooperation Enhances Robustness of Coexistence in Spatially Structured Consortia (Xinying Ren, Richard M Murray, Submitted, 2019 European Control Conference)
- Role of interaction network topology in controlling microbial population in consortia (Xinying Ren, Richard M Murray, To appear, 2018 Conference on Decision and Control (CDC))
- Proof of concept continuous event logging in living cells (Andrey Shur, Richard M Murray, 2018 Synthetic Biology: Engineering, Evolution and Design (SEED) Conference)
- Single day construction of multi-gene circuits with 3G assembly (Andrew D Halleran, Anandh Swaminathan, Richard M Murray, 2018 Synthetic Biology: Engineering, Evolution and Design (SEED) Conference)
- Long-distance communication in synthetic bacterial consortia through active signal propagation (James M Parkin, Richard M Murray, 2018 Synthetic Biology: Engineering, Evolution and Design (SEED) Conference)
- Control of bacterial population density with population feedback and molecular sequestration (Reed D McCardell, Shan Huang, Leopold N Green, Richard M Murray, 2018 Winter q-bio)
- Cell-free and in vivo characterization of Lux, Las, and Rpa quorum activation systems in E. coli (Andrew Halleran, Richard M. Murray, To appear, ACS Synthetic Biology, July 2017)
- Population regulation in microbial consortia using dual feedback control (Xinying Ren, Ania-Ariadna Baetica, Anandh Swaminathan, Richard M. Murray, Submitted, 2017 Conference on Decision and Control (CDC))
- Quantitative Modeling of Integrase Dynamics Using a Novel Python Toolbox for Parameter Inference in Synthetic Biology (Anandh Swaminathan, Victoria Hsiao, Richard M Murray, 2017 Synthetic Biology: Engineering, Evolution, and Design (SEED) Conference)
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