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/NIGMS, Sponsor Award ID: R35GM136324
  • September 19, 2011 - June 30, 2020 - Host management of the mitochondrial genome, Principal Investigator. Sponsor: NIH/NIGMS, Sponsor Award ID: R01GM120005
  • July 1, 1986 - June 30, 2020 - Developmental Programs of Cell Cycle Control, Principal Investigator. Sponsor: NIH/NIGMS, Sponsor Award ID: R37GM037193
  • September 19, 2011 - June 30, 2016 - The genetic basis for tissue specific sensitivities to mitochondrial stress, Principal Investigator. Sponsor: NIH/NIEHS, 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. Seller CA, Cho CY, O'Farrell PH Rapid embryonic cell cycles defer the establishment of heterochromatin by Eggless/SetDB1 in Drosophila.  View on PubMed
  2. Seller CA, O'Farrell PH Rif1 prolongs the embryonic S phase at the Drosophila mid-blastula transition.  View on PubMed
  3. Duronio RJ, O'Farrell PH, Sluder G, Su TT Sophisticated lessons from simple organisms: appreciating the value of curiosity-driven research.  View on PubMed
  4. Yu Z, O'Farrell PH, Yakubovich N, DeLuca SZ The Mitochondrial DNA Polymerase Promotes Elimination of Paternal Mitochondrial Genomes.  View on PubMed
  5. Yuan K, Seller CA, Shermoen AW, O'Farrell PH Timing the Drosophila Mid-Blastula Transition: A Cell Cycle-Centered View.  View on PubMed
  6. Ma H, O'Farrell PH Selfish drive can trump function when animal mitochondrial genomes compete.  View on PubMed
  7. Yuan K, O'Farrell PH TALE-light imaging reveals maternally guided, H3K9me2/3-independent emergence of functional heterochromatin in Drosophila embryos.  View on PubMed
  8. O'Farrell PH Growing an Embryo from a Single Cell: A Hurdle in Animal Life.  View on PubMed
  9. Ma H, O'Farrell PH Selections that isolate recombinant mitochondrial genomes in animals.  View on PubMed
  10. Yuan K, O'Farrell PH Cyclin B3 is a mitotic cyclin that promotes the metaphase-anaphase transition.  View on PubMed
  11. Farrell JA, O'Farrell PH From egg to gastrula: how the cell cycle is remodeled during the Drosophila mid-blastula transition.  View on PubMed
  12. Ma H, Xu H, O'Farrell PH Transmission of mitochondrial mutations and action of purifying selection in Drosophila melanogaster.  View on PubMed
  13. O'Farrell PH Two-dimensional gel electrophoresis and the beginning of proteomics.  View on PubMed
  14. Yuan K, Shermoen AW, O'Farrell PH Illuminating DNA replication during Drosophila development using TALE-lights.  View on PubMed
  15. Farrell JA, O'Farrell PH Mechanism and regulation of Cdc25/Twine protein destruction in embryonic cell-cycle remodeling.  View on PubMed
  16. Yuan K, Farrell JA, O'Farrell PH Different cyclin types collaborate to reverse the S-phase checkpoint and permit prompt mitosis.  View on PubMed
  17. Farrell JA, Shermoen AW, Yuan K, O'Farrell PH Embryonic onset of late replication requires Cdc25 down-regulation.  View on PubMed
  18. DeLuca SZ, O'Farrell PH Barriers to male transmission of mitochondrial DNA in sperm development.  View on PubMed
  19. Shermoen AW, McCleland ML, O'Farrell PH Developmental control of late replication and S phase length.  View on PubMed
  20. Yakubovich N, Silva EA, O'Farrell PH Nitric oxide synthase is not essential for Drosophila development.  View on PubMed

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