Jack H. Skirball Center for Chemical Biology and Proteomics
Salk Institute for Biological Studies
Gerald F. Joyce is a Professor at the Salk Institute in La Jolla, California. He also is Institute Director of the Genomics Institute of the Novartis Research Foundation (GNF) in La Jolla. Dr. Joyce received his BA from the University of Chicago in 1978 and both an MD and PhD from the University of California, San Diego in 1984. He carried out postgraduate medical training at Scripps Mercy Hospital in San Diego and postdoctoral research training at The Salk Institute before joining the faculty of The Scripps Research Institute in 1989. In 2017 he moved his laboratory to the Salk Institute, where it is part of the Jack H. Skirball Center for Chemical Biology and Proteomics.
Dr. Joyce’s research involves the test-tube evolution of functional nucleic acid molecules and their potential application in clinical diagnostics and therapeutics. He has a longstanding interest in the origins of life and the role of RNA in the early history of life on Earth. His research 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.
Dr. Joyce 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.
"Reconstructing RNA-based Life: RNA-Catalyzed Polymerization and Replication of RNA"
According to the RNA world hypothesis, ancestors of extant life stored and expressed genetic information in RNA molecules that were replicated by an RNA polymerase ribozyme. In an effort to reconstruct RNA-based life, in vitro evolution was used to improve the activity and generality of an RNA polymerase ribozyme by selecting for variants that can synthesize functional RNA molecules from an RNA template using the four nucleoside 5´-triphosphates (NTPs). The resulting polymerase can synthesize a variety of complex structured RNAs, including aptamers, ribozymes, and tRNA. Furthermore, the polymerase can replicate and amplify short RNA templates in an RNA-catalyzed form of the polymerase chain reaction.
The evolved RNA polymerase ribozyme also has the ability to synthesize DNA molecules from an RNA template using the four dNTPs, an activity would have been crucial for the transition from RNA genomes to DNA genomes during the early history of life on Earth. Finally, the RNA polymerase ribozyme was divided into three fragments that assemble non-covalently to form a functional enzyme. The non-covalently assembled ribozyme has the ability to synthesize each of its three component fragments. Like the mini-variants of Qß RNA that were obtained by Spiegelman 50 years ago, the RNA polymerase ribozyme is the product of “an extracellular Darwinian experiment”, but also like Spiegelman’s mini-variants, the ribozyme is not (yet) “a self-duplicating nucleic acid molecule”.