Patrick H. O'Farrell, PhD

Professor, Department of Biochemistry and Biophysics, UCSF

Cancer Center Program Memberships

Affiliate Member

Research Summary

We are interested in the decoding of biological information to produce functional structures at the level of cells and organisms. We focus on the control of the cell cycle during development using Drosophila genetics, molecular biology and fancy microscopy. We are examining temporal coordination of early embryonic cell cycles with development. Having found that slowing early rapid cell cycles is due to prolongation of S phase, the period of DNA replication, we are studying this control. This prolongation of S phase is tightly integrated with a developmental program of chromatin changes that introduces epigenetic controls. Using GFP tagged proteins marking molecular hallmarks of these events, we are able to watch them occur in real time in embryos and to probe the processes that regulate their onset.

A newer effort explores the genetics and biology of the mitochondria. Our principle interest is in a newly recognized mystery. The mitochondrial genome encodes functions that benefit the host rather than propagation and transmission of the mitochondrial genome. This would not be problem if evolution of this genome were based on the usual selection for fit organisms as Darwin suggests. However, we found that selection is based on the ability of genomes to compete for transmission from one generation to the next. This ought to select for selfish genes promoting genome success. To achieve the real outcome, the host manipulates the competition to favor genes to its benefit. We are trying to understand how this managed evolution is achieved.

Education

McGill University, Montreal, Quebec, B.Sc., 1969, Genetics
University of Colorado, Boulder, Ph.D., 1974, Cell & Dev Biol
University of California San Francisco, Postdoc, 1978

Professional Experience

1969-1974
Grad. Student: lab of Jacques Pene (1969-72) & David Hirsh (1973 -74). Development of 2-D gel electrophoresis; pleiotropic control. MCD Biology, University of Colorado
1974-1976
Postdoctoral studies with Gordon Tomkins. Regulation of translational accuracy; hormonal control; expression of recombinant DNA. Dept of Biochemistry, UCSF
1976-1979
Postdoctoral studies with Bruce Alberts. Stringency of gene inactivation; new preparative separation technology. Dept of Biochemistry, UCSF
1979-1985
Assistant Professor, Department of Biochemistry & Biophysics, UCSF
1985-1989
Associate Professor, Department of Biochemistry & Biophysics, UCSF
1986
Sabbatical research, with Dr. Christiane Nüsslein-Volhard, Tubingen, FRG
1989-present
Professor, Department of Biochemistry & Biophysics, UCSF
1995-1996
Sabbatical research with Dr. Gerald Rubin, University of California, Berkeley

Honors & Awards

1975-78
Fellow of the Jane Coffin Childs Memorial Fund for Medical Research
1978-1979
Senior Fellow of the California Division of the American Cancer Society
1986
Award - Sarstedt Research Prize for the development of electrophoretic separations
1989
Chairman of the Biological Regulatory Mechanism Gordon Conference
1998
Chairman of the Molecular Genetics Gordon Conference
1999-2007
Scientific Review Board, Howard Hughes Institute
1998
Advisory Panel to the NCI
2006
Outstanding mentorship award, Posdoc. Scholars Assoc. UCSF
2009
UMDF – chairman's prize for top proposal
2009
Elected to American Academy of Arts and Sciences
2010
Member of the NIH College of CSR Reviewers.
2010-2020
MERIT award from NIH/NIGMS
2012
Honorary Doctorate of Science, Univ. of Lethbridge
2014
ABRF Award for Outstanding Contributions to Biomolecular Technologies
2017
Member, National Academy of Sciences

Selected Publications

O'Farrell PH. Quiescence: early evolutionary origins and universality do not imply uniformity. Philos Trans R Soc Lond B Biol Sci. 2011 Dec 27; 366(1584):3498-507.
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O'Farrell PH. The pre-omics era: the early days of two-dimensional gels. Proteomics. 2008 Dec; 8(23-24):4842-52.
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O'Farrell PH. Triggering the all-or-nothing switch into mitosis. Trends Cell Biol. 2001 Dec; 11(12):512-9.
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O'Farrell PH. Conserved responses to oxygen deprivation. J Clin Invest. 2001 Mar; 107(6):671-4.
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