UC San Diego

Gene regulatory networks lay at the foundation of biological function and are responsible for driving the diverse cellular decision making processes required to sustain life. Developing a comprehensive understanding of cellular function will require a quantitative description of the dynamics of these underlying interactions. The ability to design synthetic gene circuits offers the exciting prospect of prototyping new genetic subsystems inspired by the inherently complex networks of natural organisms. An increasingly vivid representation of the design principles that drive biological function is assembled through the systematic design and characterization of experimentally tractable synthetic modules of increasing complexity. The programming of living cells according to these principles will provide fundamental insights into the regulatory architecture, dynamics, and evolution of natural networks and open new avenues in biotechnology by revealing novel ways to program genetic modules. In Chapter One, I give an introduction to the genetic circuits approach by relating a survey of recent research that has been influential for me. In Chapter Two, I discuss my work on integrated "bacto -electronic" sensors that communicate over supermicrobial spatial scales. In Chapter Three, I discuss engineered gene circuits in the clinically relevant microbe S. typhimurium. In Chapter Four, I discuss a rapid and tunable post-translational coupling method for genetic circuits. In Chapter Five, I discuss designer probiotics for non-invasive cancer diagnostics. The unifying goal of these efforts is a "bottom-up" approach to building gene circuits predicted to confer a particular behavior based on engineering principles