Eschenmoser Lecture 2022

May 16, 2022
«Reconstructing RNA-based Life: RNA-Catalyzed Polymerization and Replication of RNA»

The Laboratory of Organic Chemistry is privileged to welcome its 2022 Eschenmoser Lecturer Gerald F. Joyce, professor in the Jack H. Skirball Center for Chemical Biology and Proteomics at the Salk Institute in La Jolla, California. He is currently the Chief Scientific Officer of this institution.

Professor Joyce received a bachelor’s degree from the University of Chicago in 1978 and both an M.D. and a Ph.D. from the University of California, San Diego in 1984. Following postgraduate medical training at Scripps Mercy Hospital in San Diego and postdoctoral research at the Salk Institute, he joined the faculty of The Scripps Research Institute in 1989. In 2017 he moved his laboratory to the Salk Institute.

Over the last 30 years, Joyce has pioneered the field of in vitro evolution. In the early 1990s he established that successive cycles of mutation, selection, and amplification could be used to isolate RNA and DNA molecules with tailored functions from large pools of random sequences. Such experiments drew on the ability of nucleic acids to carry information and assume well-defined structures that bind specific target molecules or catalyze discrete chemical reactions. Using this approach, he produced the first RNA enzymes that could cleave single-stranded DNA and, conversely, a metal-dependent DNA enzyme cleaving RNA.

Because in vitro evolution can be conducted rapidly, nucleic acid enzymes can be evolved at a much faster pace in the test tube than in nature. As a result, molecular evolution can now be studied in real time and novel catalysts generated. Examples of such include ribozymes that exponentially amplify other RNA molecules, make mirror-image copies of themselves, or polymerize deoxyribose, threose, and arabinose nucleic acids. A reverse transcriptase ribozyme is one of the newest achievements of the Joyce lab. Perhaps the ultimate goal for any Darwinian engineer is a system that evolves on its own. Toward that end, Joyce has produced a self-replicating in vitro system, capable of exponential growth and continuing evolution, composed entirely of RNA enzymes. This exciting discovery has opened a window onto basic evolutionary mechanisms and the origins of life on Earth. In addition to providing truly fundamental insights into the very beginnings of our own existence, synthetic RNA catalysts offer immense practical utility as diagnostic and therapeutic agents against diseases such as cancer, immune disorders, and viral infections.

Gerald Joyce has been widely recognized for his profound impact on our understanding of Darwinian evolution at the molecular level. Among other distinctions, he received the National Academy of Sciences Award in Molecular Biology (1994), the Pfizer Award in Enzyme Chemistry (1995), the Hans Sigrist Prize from the University of Bern (1997), the H.C. Urey Award (2005), the Dannie-Heineman Prize from the Göttingen Academy of Sciences and Humanities (2009), and the Stanley Miller Medal (2010). Professor 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, and a foreign member of the Royal Swedish Academy of Sciences.