Synthetic Biology: from Bacteria to Stem Cells

Ron Weiss, Department of Electrical Engineering, Princeton University, Princeton, NJ - USA

Abstract: With recent advances in our understanding of cellular processes and improvements in DNA synthesis methods, we can now regard cells as "programmable matter." Through genetic engineering, we are equipping cells with new sophisticated capabilities for gene regulation, information processing, and communication.  These new capabilities serve as catalysts for Synthetic Biology, an emerging engineering discipline to program cell behaviors as easily as we program computers.  Synthetic biology will improve our quantitative understanding of natural biological processes and will also have biotechnology applications in areas such as biosensing, synthesis of pharmaceutical products, molecular fabrication of biomaterials and nanostructures, and tissue engineering.

In this talk, we will describe the use of computer engineering principles of abstraction, composition, and interface specifications to program cells with sensors and actuators precisely controlled by analog and digital logic circuitry.  Here we will present theoretical and experimental results from synthetic systems implemented in bacteria and higher order organisms.  We will begin by describing how information flows through synthetic transcriptional cascades in single cells by examining noise propagation, ultrasensitivity, and impedance matching.  Understanding these issues is critical for the analysis and de novo engineering of complex gene networks. We will then discuss several synthetic multicellular systems that have been programmed to exhibit unique coordinated cell behavior.  These are the pulse generator, band detector, and Conway's Game of Life.  These systems allow us to explore programmed pattern formation and observe how complex global behavior emerges from localized interactions between cells.  We will also discuss the implementation of artificial cell-cell communication and quorum sensing behavior in higher level organisms such as yeast.  Finally, we will discuss preliminary results in mouse embryonic stem cells of implementing synthetic gene networks that regulate gene expression, direct differentiation, and orchestrate artificial cell-cell communication with the ultimate goal of programmed tissue engineering.

About the speaker: Ron Weiss is an Assistant Professor of Electrical Engineering at Princeton University, and also holds a faculty appointment in the Department of Molecular Biology. He received his PhD from the Massachusetts Institute of Technology in Computer Science and Electrical Engineering (2001). His research focuses primarily on Synthetic Biology, where he programs cell behavior by constructing and modeling biochemical and cellular computing systems. A major thrust of his work is the synthesis of gene networks that are engineered to perform in vivo analog and digital logic computation. He is also interested in programming cell aggregates to perform coordinated tasks using cell-cell communication with chemical diffusion mechanisms such as quorum sensing. He has constructed and tested several novel in vivo biochemical logic circuits and intercellular communication systems.

Weiss is interested in both hands-on experimental work and in implementing software infrastructures for simulation and design work. For his work in Synthetic Biology, Weiss has received MIT's Technology Review Magazine's TR100 Award ("top 100 young innovators", 2003), was selected as a speaker for the National Academy of Engineering's Frontiers of Engineering Symposium (2003), received the E. Lawrence Keyes, Jr./Emerson Electric Company Faculty Advancement Award at Princeton University (2003), his research in Synthetic Biology was named by MIT's Technology Review Magazine as one of "10 emerging technologies that will change your world" (2004), was chosen as a finalist for the World Technology Network's Biotechnology Award (2004), and was selected as a speaker for the National Academy of Sciences Frontiers of Science Symposium (2005).  During recent years, Weiss has had several major publications in journals such as Nature, Nature Biotechnology, and PNAS.