ANALOG | Programming Biology

RESEARCH - ANALOG

The behavior of synthetic cellular systems may exhibit complex, dynamic behavior and cannot be treated as digital in general. Additionally, cellular context causes nodes within a network to become unintentionally coupled, which deteriorates the function of the system. In this project, we measure, model, and analyze dynamic behavior and effects due to cellular context in order to increase the predictability of design-oriented models, optimize the design of genetic networks for robustness to context, and create design paradigms for genetic networks that scale well.

WHAT?

WHY?

Effects due to cellular context hamper the predictability of current models and substantially deteriorates the performance of genetic circuits. Models that capture context-effects are necessary to ensure agreement between predictions and experimental results and to inform decisions about the design and optimization of robust genetic networks.

Shared resource pools cause coupling that changes the behavior of a genetic network. We create design-oriented predictive models that allow to incorporate these context effects within the design process.

Retroactivity causes a deterioration of performance due to bidirectional signals when systems are connected. Using motifs inspired by natural systems, devices may be created to insulate systems from retroactivity while maintaining signal transmission.

Project Contributors

Prof. Domitilla Del Vecchio

J. H. Cho, J. J. Collins, and W. W. Wong, “Universal Chimeric Antigen Receptors for Multiplexed and Logical Control of T Cell Responses,” Cell, in press.

N. M. L. Wong and W. W. Wong, “Engineering a Dual Small Molecule Gated ZAP70 Switch in T Cells,” ACS Synthetic Biology, vol. 7, iss. 4, 2018.

J. H. Cho, A. Okuma, D. Al-Rubaye, E. Intisar, R. P. Junghans, and W. W. Wong, “Engineering Axl specific CAR and SynNotch receptor for cancer therapy,” Scientific Reports, vol. 8, iss. 1, 2018.

M. J. Brenner, J. H. Cho, N. M. L. Wong, and W. W. Wong, “Synthetic Biology: Immunotherapy by Design,” Annual Review of Biomedical Engineering, vol. 20, iss. 1, 2018.

D. Del Vecchio, “Modularity, context-dependence, and insulation in engineered biological circuits”, Trends in Biotechnology, 2014.
A. Gyorgy, J. Jimnez, J. Yazbek, H.H. Huang, H. Chung, R. Weiss, D. Del Vecchio, “Isocost lines describe the cellular economy of genetic circuits” Biophysical Journal, August 2015.
D. Mishra, P. Rivera, A. Lin, D. Del Vecchio, R. Weiss, “A load driver device for engineering modularity in biological networks”, Nature Biotechnology, September 2014.

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