Synthetic meets cell biology

Abstract

Following a successful panel discussion at last years' American Society for Cell Biology Annual Meeting, the first minisymposium in Synthetic Cell Biology was held at this years' annual meeting in Denver. This is an exciting first for the society, and the attendance clearly supported the interest of cell biologists in applying the concepts of synthetic biology to the understanding and engineering of cells. Pamela Silver opened the session with a brief overview of the rapidly growing field of synthetic biology. She began by defining the goal of synthetic biology as making the building of biological systems faster, cheaper, and more predictable. She anticipated that the engineering of biology will be the defining technology of this century. Over 50 years of molecular and cell biology have brought us to a point where biology is much in the space where organic chemistry was 30 years ago—we understand many of the pieces and the fundamental reactions, and we are well situated to start building with biology. Indeed, the modular nature of much of cell biology offers an important starting point for the logical engineering of a wide range of useful biological systems. And DNA—the basic building material for biology—is getting increasingly cheaper to synthesize, thereby making it possible to consider creating large pieces of reprogrammed chromosomes and in some cases, whole genomes. But how do we start, and what should we build? The minisymposium offered some useful visions and guidance. For example, Silver discussed the modular nature of the control of carbon fixation in photosynthetic bacteria. She presented results from Dave Savage that indicate that it is possible to reassemble carbon-fixing units (carboxysomes in nonphotosynthetic bacteria), a first step in moving carbon fixation from one organism to another. In another series of experiments, she demonstrated the artificial assembly of RNA-based scaffolds engineered to carry out biosynthetic reactions more efficiently inside cells. Together these results represent important steps forward in programming new behaviors into cells using the modularity of biology. Ron Weiss, consistent with his background as a computer scientist turned synthetic biologist, went on to argue that the cell is a highly programmable entity. One of his goals is to create gene programs that control tissue patterning through the engineering of artificial homeostasis and timing of differentiation. One strategy to accomplish this involves a biocompiler designed to take a high-level cell behavior, abstract it into a regulatory network, and expand it into a logical operation in terms of a gene network that then instructs a robot to assemble the necessary DNA. These talks were followed by four short talks from younger investigators. Brian Goodman from Sam Reck-Peterson's lab discussed using DNA as a scaffold on which to position molecular motors for directional transport. Karmella Haynes, a new assistant professor at Arizona State University, talked about designing a collection of modules from chromatin to guide a cell to differentiation in programmable ways. Takanari Inoue presented novel intracellular logic gates that could be chemically controlled. And Clifford Wong built on the engineering parallels to analyze gene dosage and expression by analogy to band-pass filters. This session engaged many who were unfamiliar with synthetic biology and stimulated cell biologists to think about new joint applications. Our deep understanding from the years of cell biological research will play a major role in the future of synthetic biology.