Rules of Composition in Synthetic Biology Across Scales of Complexity: Theory and Tools

The goal of this project is to establish theoretical foundations and tools, grounded on mathematics, that will enable compositional design of synthetic biology circuits while accounting for context. These tools will substitute currently used ad hoc procedures that design systems in a monolithic fashion by brute force optimization of parameters, thereby allowing to scale up the complexity of systems that we can build, shorten the design cycle, and achieve quantitative performance.

Current participants: Hengyu Wang (MS student, EE) Additional participants: Manisha Kapasiawala (PhD student, BE)

Collaborators: Domitilla Del Vecchio, Jim Collins, Katie Galloway, Michael Laub (MIT) Eduardo Sontag (Northeastern) Past participants: Inigo Incer (Alumni, CMS) Zoila Jurado (Postdoc, CMS) Ayush Pandey (Alumni, CDS)

Objectives

Caltech is contributing to the following objectives for this project

• Establish tools to certify system behavior against a specification through scales of model complexity, with increased complexity required to account for undesired connectivity.
• Establish tools for subsystem specification decomposition, reducing the design problem of a multi-module system to that of its composing subsystems, thereby reducing the complexity of the parameter selection problem.

References

• Pacti: Scaling Assume-Guarantee Reasoning for System Analysis and Design. Inigo Incer, Apurva Badithela, Josefine Graebener, Piergiuseppe Mallozzi, Ayush Pandey, Sheng-Jung Yu, Albert Benveniste, Benoit Caillaud, Richard M. Murray, Alberto Sangiovanni-Vincentelli, Sanjit A. Seshia. Submitted, ACM Transactions on Cyber-Physical Systems (TCPS), Aug 2023.
• A chemical reaction network model of PURE. Zoila Jurado, Ayush Pandey, Richard M. Murray. BioRxiv preprint, 2023.
• Characterization of Integrase and Excisionase Activity in Cell-free Protein Expression System Using a Modeling and Analysis Pipeline. Ayush Pandey, Makena L. Rodriguez, William Poole, Richard M. Murray. ACS Synthetic Biology, 12(2):511–523, 2023.
• Fast and flexible simulation and parameter estimation for synthetic biology using bioscrape. Anandh Swaminathan, William Poole, Victoria Hsiao, Ayush Pandey, and Richard M. Murray. Journal of Open Source Software (JOSS), 2023.
• From Specification to Implementation: Assume-Guarantee Contracts for Synthetic Biology. Ayush Pandey, Inigo Incer, Alberto Sangiovanni-Vincentelli, Richard M. Murray. 2022 International Workshop on Biodesign Automation (IWBDA).

This research is supported by the Air Force Office of Scientific Research (AFOSR) under MURI grant FA9550-22-1-0316.

Agency: AFOSR Grant number: FA9550-22-1-0316

Start date: 1 Jul 2022 End date: 30 Jun 2027

Support: 2 graduate students Reporting: Annual reports