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.

Research Funding

  • June 1, 2020 - May 31, 2025 - Embryonic Emergence of Heterochromatin and Nuclear Supervision of Mitochondrial Genetics , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R35GM136324
  • September 19, 2011 - June 30, 2020 - Host management of the mitochondrial genome , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01GM120005
  • July 1, 1986 - June 30, 2020 - Developmental Programs of Cell Cycle Control , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R37GM037193
  • September 19, 2011 - June 30, 2016 - The genetic basis for tissue specific sensitivities to mitochondrial stress , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01ES020725

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

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

  1. Cho CY, Kemp JP, Duronio RJ, O'Farrell PH. Coordinating transcription and replication to mitigate their conflicts in early Drosophila embryos. Cell Rep. 2022 10 18; 41(3):111507.  View on PubMed
  2. Tsai PI, Korotkevich E, O'Farrell PH. Mitigation of age-dependent accumulation of defective mitochondrial genomes. Proc Natl Acad Sci U S A. 2022 08 02; 119(31):e2119009119.  View on PubMed
  3. Cho CY, Seller CA, O'Farrell PH. Temporal control of late replication and coordination of origin firing by self-stabilizing Rif1-PP1 hubs in Drosophila. Proc Natl Acad Sci U S A. 2022 06 28; 119(26):e2200780119.  View on PubMed
  4. Strong IJT, Lei X, Chen F, Yuan K, O'Farrell PH. Interphase-arrested Drosophila embryos activate zygotic gene expression and initiate mid-blastula transition events at a low nuclear-cytoplasmic ratio. PLoS Biol. 2020 10; 18(10):e3000891.  View on PubMed
  5. Chiang AC, McCartney E, O'Farrell PH, Ma H. A Genome-wide Screen Reveals that Reducing Mitochondrial DNA Polymerase Can Promote Elimination of Deleterious Mitochondrial Mutations. Curr Biol. 2019 12 16; 29(24):4330-4336.e3.  View on PubMed
  6. Seller CA, Cho CY, O'Farrell PH. Rapid embryonic cell cycles defer the establishment of heterochromatin by Eggless/SetDB1 in Drosophila. Genes Dev. 2019 04 01; 33(7-8):403-417.  View on PubMed
  7. Seller CA, O'Farrell PH. Rif1 prolongs the embryonic S phase at the Drosophila mid-blastula transition. PLoS Biol. 2018 05; 16(5):e2005687.  View on PubMed
  8. 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
  9. 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
  10. 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
  11. 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
  12. 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
  13. 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
  14. Ma H, O'Farrell PH. Selections that isolate recombinant mitochondrial genomes in animals. Elife. 2015 Aug 03; 4.  View on PubMed
  15. 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
  16. 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
  17. 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
  18. O'Farrell PH. Two-dimensional gel electrophoresis and the beginning of proteomics. Clin Chem. 2014 Jul; 60(7):1012-3.  View on PubMed
  19. 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
  20. 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

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