Faculty

Gerald Joyce 
DEAN OF THE FACULTY
Professor
MOLECULAR BIOLOGY
TSRI - 1989

Joint Appointments 
CHEMISTRY

Education 
B.A., University of Chicago, 1978; M.D., University of California, San Diego, 1984; Ph.D., University of California, San Diego, 1984; Medical Internship, Mercy Hospital and Medical Center, 1984-85; Postdoctoral Fellow, The Salk Institute, 1985-88; Merck Fellow, Life Sciences Research Foundation, 1985-88; Assistant Professor, Departments of Chemistry and Molecular Biology, TSRI, 1989-92; Associate Professor, Departments of Chemistry and Molecular Biology, TSRI, 1992-96

Awards & Activities 
National Academy of Sciences Award in Molecular Biology, 1994; Pfizer Award in Enzyme Chemistry, 1995; Herbert W. Dickerman Award, 1997; Hans Sigrist Prize, 1997; Linnaeus Lecturer, Uppsala University, 2001; Member, U.S. National Academy of Sciences, 2001; Head of Faculty in Chemical Biology, Faculty 1000; Associate Editor, BioSystems; Associate Editor, Evolutionary Computation; Associate Editor, Origins of Life and Evolution of the Biosphere

Research Focus 
Directed Evolution of RNA and DNA Enzymes

My research concerns the biochemistry of RNA and the development of novel RNA and DNA enzymes through in vitro evolution. Like their protein counterparts, nucleic acid enzymes assume a well-defined structure that is responsible for their catalytic activity. Unlike proteins, however, nucleic acids are genetic molecules that can be amplified and mutated in the test tube. The members of my laboratory and I have learned to exploit the dual role of nucleic acids as both catalyst and genetic molecule to develop RNA- and DNA-based evolving systems that operate entirely in vitro. At best, we can carry out 100 "generations" of test-tube evolution in a day, employing a population of one hundred trillion nucleic acid molecules. This allows us to evolve nucleic acid enzymes far more rapidly than whole organisms evolve in nature.

Our studies of RNA-based evolution are relevant to understanding the early history of life on Earth. It is believed that an RNA-based genetic system, termed the "RNA world", preceded the DNA and protein-based genetic system that has existed for the past 3.5 billion years. Our research aims to recapitulate the biochemistry of the RNA world in the laboratory. We are using in vitro evolution to explore the catalytic potential of RNA, and especially to search for RNA enzymes that have the ability to catalyze their own replication.

Selected References 
Joyce, G.F. The antiquity of RNA-based evolution. Nature 418:214, 2002.

Paul, N. , Joyce, G.F. A self-replicating ligase ribozyme. Proc. Natl. Acad. Sci. USA 99:12733, 2002.


Paul, N., Springsteen, G. & Joyce, G.F. Conversion of a ribozyme to a deoxyribozyme through in vitro evolution. Chem. Biol. 13:329, 2006.


Shih, W.M., Quispe, J.D., Joyce, G.F. A 1.7-kilobase DNA that folds into a nanoscale octahedron. Nature 427:619, 2004.