Genetic Circuit Design: Ideas from Control Theory

Mary Dunlop, California Institute of Technology

The field of synthetic biology has recently surged as researchers discover how to manipulate genetic circuits to accomplish simple tasks. Toy problems such as blinking bacteria, cells that use digital logic to play tic-tac-toe, and bacteria that perform basic Boolean computations are all developments that have occurred within the past 5 years. Such experimental advances leave biologists and engineers alike asking the enticing question: “Can we redesign control systems in microbiological organisms?” But as this fascinating field of engineering biological systems unfolds it becomes apparent that biologists need better tools to help them understand and characterize what is actually going on within the cell. Current synthetic gene network design is driven by expert biologists whose understanding of very specific pathways enables them to develop ad hoc designs, without adding to the understanding of the field of gene circuit design as a whole.

Biological systems are an enticing area to work in because so many genetic pathways have been characterized experimentally without a systematic approach towards understanding overarching principles. Over the course of the summer I plan to begin working with a microbiological system that has been well studied experimentally, most likely utilizing the current knowledgebase on transcription factors in E. coli (http://ecotfs.lanl.gov). This project will begin the process of developing a mathematical model of gene circuit design to include feedback elements and discrete logic. Such a model will aid understanding of dynamical behaviors such as steady state and transient responses in gene circuits. Using general concepts such as feed forward and feedback loops, which are ubiquitous in biological systems, and hybrid or switched system modeling I hope to introduce more general modeling principles to the study of genetic circuits.

Abstract Author(s): Mary J. Dunlop