Synthetic Self Replicating and Evolvable Systems
Although science regards life as the outcome of physical and chemical processes, much about the origin of life remains unknown. According to one theory - the RNA world hypothesis - ancestors of extant life stored and expressed genetic information in RNA molecules that were replicated by RNA enzymes, precursors to the DNA based system of most living organisms today. My laboratory and others interested in how life arose, have endeavored to reconstruct RNA-based life in the laboratory.
My laboratory used directed evolution to obtain an RNA enzyme that copies RNA templates into complementary RNA products with robust activity and sequence generality. The enzyme can synthesize a variety of complex, structured RNAs, including those with catalytic functions. The enzyme also can replicate and amplify short RNA templates in an RNA-catalyzed form of the polymerase chain reaction. A variant of the enzyme has the ability to synthesize DNA molecules from an RNA template, an activity that would have been crucial for the transition from RNA genomes to DNA genomes during the early history of life on Earth.
We have also used directed evolution to obtain a "cross-chiral" RNA enzyme that catalyzes the RNA-templated synthesis of RNAs of opposite handedness. The enzyme can operate on a broad range of template sequences and is able to synthesize its own enantiomer by joining multiple component fragments. The homochiral and heterochiral polymerization systems offer two approaches for the synthesis and replication of functional RNAs, prerequisites for the realization of RNA-based life.
In this lecture I will discuss the RNA world hypothesis and research on reproducing in the laboratory some of the crucial features of the RNA world. I will describe some of the results of the research, including the RNA-enzymes we have made and their uses in replicating RNA in both left and right handed forms. I will also discuss some potential diagnostic and clinical applications of this research, and prospects for further progress in this field.
About the Speaker
Gerald F. Joyce is a Professor at the Salk Institute in the Skirball Center for Chemical Biology and Proteomics. At the same time he serves as Institute Director of the Genomics Institute of the Novartis Research Foundation. Prior to joining the Salk Institute, Jerry was a Professor at The Scripps Research Institute. Before that he did postgraduate medical training at Scripps Mercy Hospital and postdoctoral research at the Salk Institute.
Jerry has a longstanding interest in the origins of life and the role of RNA in the early history of life on Earth. His research involves the test-tube evolution of functional RNA and DNA molecules and their potential application in clinical diagnostics and therapeutics. It has led to the development of the first self-replicating RNA enzyme, which is capable of exponential growth and evolution. It also has led to the development of an RNA enzyme that catalyzes the polymerization and exponential amplification of other RNA molecules.
Among other honors, Jerry is a member of the U.S. National Academy of Sciences, the U.S. National Academy of Medicine, and the American Academy of Arts and Sciences. He is recipient of the U.S. National Academy of Sciences Award in Molecular Biology, the Hans Sigrist Prize from the University of Bern, and the U.S. National Academy of Sciences Award for Early Earth and Life Sciences.
Jerry received a BA from the University of Chicago and both an MD and PhD from the University of California, San Diego.