Patrick H. O'Farrell, PhD
Professor, Department of Biochemistry and Biophysics, UCSF
Cancer Center Program Memberships
Affiliate MemberResearch 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
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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
- Seller CA, Cho CY, O'Farrell PH. Rapid embryonic cell cycles defer the establishment of heterochromatin by Eggless/SetDB1 in Drosophila. Genes Dev. 2019 Feb 26.
View on PubMed - Seller CA, O'Farrell PH. Rif1 prolongs the embryonic S phase at the Drosophila mid-blastula transition. PLoS Biol. 2018 May; 16(5):e2005687.
View on PubMed - Duronio RJ, O'Farrell PH, Sluder G, Su TT. Sophisticated lessons from simple organisms: appreciating the value of curiosity-driven research. Dis Model Mech. 2017 12 19; 10(12):1381-1389.
View on PubMed - Yu Z, O'Farrell PH, Yakubovich N, DeLuca SZ. The Mitochondrial DNA Polymerase Promotes Elimination of Paternal Mitochondrial Genomes. Curr Biol. 2017 Apr 03; 27(7):1033-1039.
View on PubMed - Yuan K, Seller CA, Shermoen AW, O'Farrell PH. Timing the Drosophila Mid-Blastula Transition: A Cell Cycle-Centered View. Trends Genet. 2016 08; 32(8):496-507.
View on PubMed - Ma H, O'Farrell PH. Selfish drive can trump function when animal mitochondrial genomes compete. Nat Genet. 2016 07; 48(7):798-802.
View on PubMed - Yuan K, O'Farrell PH. TALE-light imaging reveals maternally guided, H3K9me2/3-independent emergence of functional heterochromatin in Drosophila embryos. Genes Dev. 2016 Mar 01; 30(5):579-93.
View on PubMed - O'Farrell PH. Growing an Embryo from a Single Cell: A Hurdle in Animal Life. Cold Spring Harb Perspect Biol. 2015 Aug 07; 7(11).
View on PubMed - Ma H, O'Farrell PH. Selections that isolate recombinant mitochondrial genomes in animals. Elife. 2015 Aug 03; 4.
View on PubMed - Yuan K, O'Farrell PH. Cyclin B3 is a mitotic cyclin that promotes the metaphase-anaphase transition. Curr Biol. 2015 Mar 16; 25(6):811-816.
View on PubMed - Farrell JA, O'Farrell PH. From egg to gastrula: how the cell cycle is remodeled during the Drosophila mid-blastula transition. Annu Rev Genet. 2014; 48:269-94.
View on PubMed - Ma H, Xu H, O'Farrell PH. Transmission of mitochondrial mutations and action of purifying selection in Drosophila melanogaster. Nat Genet. 2014 Apr; 46(4):393-7.
View on PubMed - O'Farrell PH. Two-dimensional gel electrophoresis and the beginning of proteomics. Clin Chem. 2014 Jul; 60(7):1012-3.
View on PubMed - Yuan K, Shermoen AW, O'Farrell PH. Illuminating DNA replication during Drosophila development using TALE-lights. Curr Biol. 2014 Feb 17; 24(4):R144-5.
View on PubMed - Farrell JA, O'Farrell PH. Mechanism and regulation of Cdc25/Twine protein destruction in embryonic cell-cycle remodeling. Curr Biol. 2013 Jan 21; 23(2):118-26.
View on PubMed - Yuan K, Farrell JA, O'Farrell PH. Different cyclin types collaborate to reverse the S-phase checkpoint and permit prompt mitosis. J Cell Biol. 2012 Sep 17; 198(6):973-80.
View on PubMed - Farrell JA, Shermoen AW, Yuan K, O'Farrell PH. Embryonic onset of late replication requires Cdc25 down-regulation. Genes Dev. 2012 Apr 01; 26(7):714-25.
View on PubMed - DeLuca SZ, O'Farrell PH. Barriers to male transmission of mitochondrial DNA in sperm development. Dev Cell. 2012 Mar 13; 22(3):660-8.
View on PubMed - 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.
View on PubMed - Shermoen AW, McCleland ML, O'Farrell PH. Developmental control of late replication and S phase length. Curr Biol. 2010 Dec 07; 20(23):2067-77.
View on PubMed