Bio-QuBIC: Designer Gene Networks for Biocomputing Applications

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EIA-0130331James.J. CollinsBoston UniversityTitle: Designer Gene Networks for Biocomputing ApplicationsMany fundamental cellular processes are governed by genetic networks which employ 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. This project involves the use of techniques from nonlinear dynamics and molecular biology to model, design and construct synthetic gene networks for biocomputing applications. Here biocomputing is defined as representing the ability of cells to make decisions based on external stimuli, and in this context, synthetic gene networks can be viewed as "controllers" for living cells. In this project, a rapidly switching genetic toggle switch is being modeled and constructed in bacterial cells. The genetic toggle switch, which is a fundamental unit of biocomputing memory storage, can be flipped between two stable expression states using transient chemical or thermal stimuli. In addition, as part of this project, synthetic gene networks based on more complicated logic gates (i.e., AND and OR gates) are being designed, modeled and constructed in bacterial cells. These circuits can function as sensors of multiple transient signals, and form the basis for general control schemes requiring an "if/then" structure.Synthetic gene networks represent a first step towards logical cellular control, whereby biological processes can be manipulated or monitored at the DNA level. Ultimately, synthetic gene circuits encoded into DNA, might be "downloaded" into cells creating, in effect, a "wet" nano-robot. These cellular robots could be utilized for a variety of functions, including in vivo biosensing, autonomously synthesizing complex biomaterials, executing programmed cell death, and interfacing with microelectronic circuits by transducing biochemical events to and from the electronics.