CAREER: Cellular control through the development of engineered gene circuits

University Of California-San Diego, La Jolla CA

Investigators

Abstract

0239165 Hasty Many fundamental cellular processes are governed by a genetic circuitry that employs protein-DNA interactions in regulating function. The biochemistry of the feedback loops associated with protein-DNA interactions leads to nonlinear effects, and the tools of nonlinear analysis become invaluable. In this project synthetic gene oscillator is being modeled and constructed in bacterial cells. The PI intends to couple the oscillator to an intrinsic periodic cellular process, which could lead to possible strategies for entraining or inducing network oscillations in cellular protein levels, and prove useful in the design of networks that interact with cellular processes that require amplification or precise timing. A multi-gene memory-based synthetic network that can function as a sensor of multiple transient signals, and thus form the basis for general control schemes requiring an "if/then" structure, will also be designed and constructed. The proposed engineered gene circuits will lead to testable predictions regarding the current understanding of complex biological networks. This ability to design synthetic gene networks offers the exciting prospect of extracting carefully chosen subsystems from natural organisms, and focusing both modeling and experimental effort on determination of the behavior of the subsystems in isolation. The long-range goal of such work would be to assemble increasingly complete models of the behavior of natural systems, while maintaining at each stage the ability to test models in a tractable experimental system. The power of this approach is that it can be used to study simplified systems in order to gain insight into the general "modules" of gene regulation. These modules include sub-networks that act as switches or oscillators, as well as networks that act to communicate across a population of cells. Work stemming from this proposal will impact education through the following projects: (i) Development of systems biology curricula for the Bioinformatics Program. To this end, research from engineered gene circuits will be used to form the basis for the systems biology curricula for undergraduate and graduate students. (ii) Development of an elementary school science program. This program will be developed in a school with a large minority component within the San Diego Unified School District. (iii) Recruitment of REU students. The PI will actively recruit two students per summer from the NSF Research Experiences for Undergraduates (REU) Program.