Molecular Programming Project

This is a joint project with Erik Winfree (PI), Shuki Bruck, Eric Klavins (UW), Niles Pierce and Paul Rothemund, funded by the NSF Expeditions program. This page primarily describes the work done in Richard Murray's group; see the MPP homepage for a description of the complete project.

Current participants: Dan Siegal (-Gaskins) (postdoc, BE → Schafer Corp) Anu Thubagere (PhD student, BE) Sean Sanchez (research technician)*

Past participants: Dionysios Barmpoutis (PhD student, CNS) Fei Chen (undergraduate, Bi) Nadine Dabby (PhD student, CNS) Mattius Falk (SURF) Juan Flores-Quijano (SURF) Elisa Franco (PhD student, CDS) Giulia Giordano (SURF) Aurelija Grigonyte (SURF) Shaunak Kar (SURF)

Ishan Kheterpal (SURF) Jongmin Kim (postdoc, BE) Patrik Lundin (SURF) Monica Li (SURF) Andrew Ng (SURF) Arjun Ravikumar (SURF) Rohit Sharma (SURF) Christopher Sturk (SURF, Lund U)

Objectives

Schematic for a positive rate regulator (a) and a negative rate regulator (b). The negative rate regulator on the right works by creating two transcripts that are complementary to teach other and also contain sequences complementary to an activator strand for the "genelets" T1:A1 and T2:A2. If one of the templates produces excess transcripts compared to the other, the excess strands will strip off the activators, downregulating the appropriate genelet. The positive rate regulator works in a similar fashion, except the outputs from the genelets cross upregulate.

The long term goal of the Molecular Programming Project is to establish a fundamental approach to the design of complex molecular and chemical systems based on the principles of computer science. The focus of our study, molecular programs, are collections of molecules that may perform a computation, fabricate an object, or control a system of molecular sensors and actuators. This project aims to develop tools and theories for molecular programming--such as programming languages and compilers--that will enable systematic design and implementation in the laboratory.

Current work includes:

• Developing in vitro transcriptional circuits capable of equalizing the rates of production of transcripts (Franco, Chen)
• Modeling and analyzing the role of crosstalk in biological circuits (Barmpoutis)
• Modeling, characterization and interconnection of transcriptional oscillators (Franco, Winfree)

Publications

Journal

• Timing molecular motion and production with a synthetic transcriptional clock, E. Franco, E. Friedrichs, J. Kim, R. Jungmann, R. Murray, E. Winfree, F. C. Simmel. Proceedings of the National Academy of Science (PNAS), 2011.

Conference

• Feedback architectures to regulate flux of components in artificial gene networks, Giulia Giordano, Elisa Franco and Richard M. Murray. American Control Conference (ACC), 2013. Submitted
• Quantifying Crosstalk in Biochemical Systems, Enoch Yeung, Jongmin Kim, Ye Yuan, Jorge Goncalves and Richard M. Murray. Conference on Decision and Control (CDC), 2012.
• Analysis and design of a synthetic transcriptional network for exact adaptation, Jongmin Kim and Richard M. Murray. IEEE Biomedical Circuits and Systems (BioCAS) Conference, 2011.
• Tuning a synthetic in vitro oscillator using control-theoretic tools, Christopher Sturk, Elisa Franco, Richard M Murray. Conference on Decision and Control (CDC), 2010.
• Design of insulating devices for in vitro synthetic circuits, Elisa Franco, Domitilla Del Del Vecchio, Richard M Murray. Conference on Decision and Control (CDC), 2009.
• Design and performance of in vitro transcription rate regulatory circuit, Elisa Franco, Richard M Murray. Conference on Decision and Control (CDC), 2008.