Genetic Process Engineering
Genetic Process Engineering
In this chapter we present an engineering discipline to obtain complex, predictable, and reliable cell behaviors by embedding biochemical logic circuits and programmed intercellular communications into cells. To accomplish this goal, we provide a well-characterized component library, a biocircuit design methodology, and software design tools. Using the cellular gates,we introduce genetic process engineering, a methodology for modifying the DNA encoding of existing genetic elements to achieve the desired input/output behavior for constructing reliable circuits of significant complexity.We also describe BioSpice, a prototype software tool for biocircuit design that supports both static and dynamic simulations and analysis of singlecell environments and small cell aggregates. The goal of our research is to lay the foundations of an engineering discipline for building novel living systems with well-defined purposes and behaviors using standardized, well-characterized components. Cells are miniature, energy efficient, self-reproduce, and can manufacture biochemical products. These unique characteristics make cells attractive for many novel applications that require precise programmed control over the behavior of the cells. The applications include nanoscale fabrication, embedded intelligence in materials, sensor/effector arrays, patterned biomaterial manufacturing, improved pharmaceutical synthesis, programmed therapeutics, and as a sophisticated tool for in vivo studies of genetic regulatory networks. These applications require synthesis of sophisticated and reliable cell behaviors that instruct cells to make logic decisions based on factors such as existing environmental conditions and current cell state. For example, a cell may be programmed to secrete particular timed sequences of biochemicals depending on the type of messages sent by its neighbors. The approach proposed here for engineering the requisite precision control is to embed internal computation and programmed intercellular communications into the cells. The challenge is to provide robust computation and communications using a substrate where reliability and reproducible results are difficult to achieve. Biological organisms as an engineering substrate are currently difficult to modify and control because of the poor understanding of their complexity. Genetic modifications to cells often result in unpredictable and unreliable behavior. A single Escherichia coli bacterial cell contains approximately 1010 active molecules, about 107 of which are protein molecules.
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