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Patrick O'Farrell, PhD

TitleProfessor
InstitutionUniversity of California San Francisco
DepartmentBiochemistry and Biophysics
Address600 16th St
San Francisco CA 94158
Phone415-476-4707
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    Collapse Overview 
    Collapse Overview
    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.


    Collapse Research 
    Collapse Research Activities and Funding
    Host management of the mitochondrial genome
    NIH/NIGMS R01GM120005Sep 19, 2011 - Jun 30, 2020
    Role: Principal Investigator
    The genetic basis for tissue specific sensitivities to mitochondrial stress
    NIH/NIEHS R01ES020725Sep 19, 2011 - Jun 30, 2016
    Role: Principal Investigator
    Nitric Oxide Signaling in Hypoxia and Immunity in Drosophila
    NIH/NIGMS R01GM086854Mar 1, 2000 - Jul 31, 2013
    Role: Principal Investigator
    Nitric Oxide and Responses to Hypoxia in Drosophila
    NIH/NIAID R01AI060102Mar 1, 2000 - Sep 29, 2008
    Role: Principal Investigator
    NITRIC OXIDE AND RESPONSES TO HYPOXIA IN DROSOPHILA
    NIH/NIGMS R01GM060988Mar 1, 2000 - Apr 14, 2004
    Role: Principal Investigator
    Developmental Programs of Cell Cycle Control
    NIH/NIGMS R37GM037193Jul 1, 1986 - Jun 30, 2020
    Role: Principal Investigator
    Developmental Programs of Cell Cycle Control
    NIH/NIGMS R01GM037193Jul 1, 1986 - Jun 30, 2010
    Role: Principal Investigator

    Collapse Bibliographic 
    Collapse Publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
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    1. Seller CA, O'Farrell P. Rif1 prolongs the embryonic S phase at the Drosophila mid-blastula transition. PLoS Biol. 2018 May 10; 16(5):e2005687. PMID: 29746464.
      View in: PubMed
    2. Duronio RJ, O'Farrell P, Sluder G, Su TT. Sophisticated lessons from simple organisms: appreciating the value of curiosity-driven research. Dis Model Mech. 2017 Dec 19; 10(12):1381-1389. PMID: 29259023.
      View in: PubMed
    3. Yu Z, O'Farrell P, Yakubovich N, DeLuca SZ. The Mitochondrial DNA Polymerase Promotes Elimination of Paternal Mitochondrial Genomes. Curr Biol. 2017 Apr 03; 27(7):1033-1039. PMID: 28318978.
      View in: PubMed
    4. Yuan K, Seller CA, Shermoen AW, O'Farrell P. Timing the Drosophila Mid-Blastula Transition: A Cell Cycle-Centered View. Trends Genet. 2016 08; 32(8):496-507. PMID: 27339317.
      View in: PubMed
    5. Ma H, O'Farrell P. Selfish drive can trump function when animal mitochondrial genomes compete. Nat Genet. 2016 07; 48(7):798-802. PMID: 27270106; PMCID: PMC4925267 [Available on 12/06/16].
    6. Yuan K, O'Farrell P. 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. PMID: 26915820; PMCID: PMC4782051.
    7. O'Farrell P. Growing an Embryo from a Single Cell: A Hurdle in Animal Life. Cold Spring Harb Perspect Biol. 2015 Aug 07; 7(11). PMID: 26254311.
      View in: PubMed
    8. Ma H, O'Farrell P. Selections that isolate recombinant mitochondrial genomes in animals. Elife. 2015 Aug 03; 4. PMID: 26237110; PMCID: PMC4584245.
    9. Yuan K, O'Farrell P. Cyclin B3 is a mitotic cyclin that promotes the metaphase-anaphase transition. Curr Biol. 2015 Mar 16; 25(6):811-816. PMID: 25754637.
      View in: PubMed
    10. Farrell JA, O'Farrell P. From egg to gastrula: how the cell cycle is remodeled during the Drosophila mid-blastula transition. Annu Rev Genet. 2014; 48:269-94. PMID: 25195504; PMCID: PMC4484755.
    11. Ma H, Xu H, O'Farrell P. Transmission of mitochondrial mutations and action of purifying selection in Drosophila melanogaster. Nat Genet. 2014 Apr; 46(4):393-7. PMID: 24614071; PMCID: PMC4091738.
    12. O'Farrell P. Two-dimensional gel electrophoresis and the beginning of proteomics. Clin Chem. 2014 Jul; 60(7):1012-3. PMID: 24568796.
      View in: PubMed
    13. Yuan K, Shermoen AW, O'Farrell P. Illuminating DNA replication during Drosophila development using TALE-lights. Curr Biol. 2014 Feb 17; 24(4):R144-5. PMID: 24556431; PMCID: PMC3977024.
    14. Farrell JA, O'Farrell P. Mechanism and regulation of Cdc25/Twine protein destruction in embryonic cell-cycle remodeling. Curr Biol. 2013 Jan 21; 23(2):118-26. PMID: 23290551; PMCID: PMC4091758.
    15. Yuan K, Farrell JA, O'Farrell P. Different cyclin types collaborate to reverse the S-phase checkpoint and permit prompt mitosis. J Cell Biol. 2012 Sep 17; 198(6):973-80. PMID: 22965907; PMCID: PMC3444785.
    16. Farrell JA, Shermoen AW, Yuan K, O'Farrell P. Embryonic onset of late replication requires Cdc25 down-regulation. Genes Dev. 2012 Apr 01; 26(7):714-25. PMID: 22431511; PMCID: PMC3323882.
    17. DeLuca SZ, O'Farrell P. Barriers to male transmission of mitochondrial DNA in sperm development. Dev Cell. 2012 Mar 13; 22(3):660-8. PMID: 22421049; PMCID: PMC3306594.
    18. O'Farrell P. 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. PMID: 22084377; PMCID: PMC3203459.
    19. Shermoen AW, McCleland ML, O'Farrell P. Developmental control of late replication and S phase length. Curr Biol. 2010 Dec 07; 20(23):2067-77. PMID: 21074439; PMCID: PMC3108027.
    20. Yakubovich N, Silva EA, O'Farrell P. Nitric oxide synthase is not essential for Drosophila development. Curr Biol. 2010 Feb 23; 20(4):R141-2. PMID: 20178753; PMCID: PMC2861863.
    21. O'Farrell P. Patrick H. O'Farrell. Curr Biol. 2010 Feb 23; 20(4):R133-4. PMID: 20213891; PMCID: PMC2869091.
    22. McCleland ML, Shermoen AW, O'Farrell P. DNA replication times the cell cycle and contributes to the mid-blastula transition in Drosophila embryos. J Cell Biol. 2009 Oct 05; 187(1):7-14. PMID: 19786576; PMCID: PMC2762091.
    23. Dijkers PF, O'Farrell P. Dissection of a hypoxia-induced, nitric oxide-mediated signaling cascade. Mol Biol Cell. 2009 Sep; 20(18):4083-90. PMID: 19625446; PMCID: PMC2743626.
    24. McCleland ML, Farrell JA, O'Farrell P. Influence of cyclin type and dose on mitotic entry and progression in the early Drosophila embryo. J Cell Biol. 2009 Mar 09; 184(5):639-46. PMID: 19273612; PMCID: PMC2686416.
    25. Stroschein-Stevenson SL, Foley E, O'Farrell P, Johnson AD. Phagocytosis of Candida albicans by RNAi-treated Drosophila S2 cells. Methods Mol Biol. 2009; 470:347-58. PMID: 19089394.
      View in: PubMed
    26. O'Farrell P. The pre-omics era: the early days of two-dimensional gels. Proteomics. 2008 Dec; 8(23-24):4842-52. PMID: 19003855; PMCID: PMC2731566.
    27. Xu H, DeLuca SZ, O'Farrell P. Manipulating the metazoan mitochondrial genome with targeted restriction enzymes. Science. 2008 Jul 25; 321(5888):575-7. PMID: 18653897; PMCID: PMC2754248.
    28. Lee SJ, Feldman R, O'Farrell P. An RNA interference screen identifies a novel regulator of target of rapamycin that mediates hypoxia suppression of translation in Drosophila S2 cells. Mol Biol Cell. 2008 Oct; 19(10):4051-61. PMID: 18653470; PMCID: PMC2555944.
    29. Hickson GR, O'Farrell P. Anillin: a pivotal organizer of the cytokinetic machinery. Biochem Soc Trans. 2008 Jun; 36(Pt 3):439-41. PMID: 18481976; PMCID: PMC2695931.
    30. McCleland ML, O'Farrell P. RNAi of mitotic cyclins in Drosophila uncouples the nuclear and centrosome cycle. Curr Biol. 2008 Feb 26; 18(4):245-54. PMID: 18291653; PMCID: PMC2698964.
    31. Hickson GR, O'Farrell P. Rho-dependent control of anillin behavior during cytokinesis. J Cell Biol. 2008 Jan 28; 180(2):285-94. PMID: 18209105; PMCID: PMC2213597.
    32. Dijkers PF, O'Farrell P. Drosophila calcineurin promotes induction of innate immune responses. Curr Biol. 2007 Dec 04; 17(23):2087-93. PMID: 18060786; PMCID: PMC2180389.
    33. Saleh MC, van Rij RP, Hekele A, Gillis A, Foley E, O'Farrell P, Andino R. The endocytic pathway mediates cell entry of dsRNA to induce RNAi silencing. Nat Cell Biol. 2006 Aug; 8(8):793-802. PMID: 16862146; PMCID: PMC2731564.
    34. Hickson GR, Echard A, O'Farrell P. Rho-kinase controls cell shape changes during cytokinesis. Curr Biol. 2006 Feb 21; 16(4):359-70. PMID: 16488869; PMCID: PMC1525334.
    35. Stroschein-Stevenson SL, Foley E, O'Farrell P, Johnson AD. Identification of Drosophila gene products required for phagocytosis of Candida albicans. PLoS Biol. 2006 Jan; 4(1):e4. PMID: 16336044; PMCID: PMC1310651.
    36. Echard A, Hickson GR, Foley E, O'Farrell P. Terminal cytokinesis events uncovered after an RNAi screen. Curr Biol. 2004 Sep 21; 14(18):1685-93. PMID: 15380073; PMCID: PMC2899696.
    37. Foley E, O'Farrell P. Functional dissection of an innate immune response by a genome-wide RNAi screen. PLoS Biol. 2004 Aug; 2(8):E203. PMID: 15221030; PMCID: PMC434151.
    38. O'Farrell P, Stumpff J, Su TT. Embryonic cleavage cycles: how is a mouse like a fly? Curr Biol. 2004 Jan 06; 14(1):R35-45. PMID: 14711435; PMCID: PMC2712630.
    39. Hériché JK, Ang D, Bier E, O'Farrell P. Involvement of an SCFSlmb complex in timely elimination of E2F upon initiation of DNA replication in Drosophila. BMC Genet. 2003 Jun 04; 4:9. PMID: 12787468; PMCID: PMC161817.
    40. Parry DH, Hickson GR, O'Farrell P. Cyclin B destruction triggers changes in kinetochore behavior essential for successful anaphase. Curr Biol. 2003 Apr 15; 13(8):647-53. PMID: 12699620; PMCID: PMC2749715.
    41. Echard A, O'Farrell P. The degradation of two mitotic cyclins contributes to the timing of cytokinesis. Curr Biol. 2003 Mar 04; 13(5):373-83. PMID: 12620185; PMCID: PMC2754242.
    42. Teodoro RO, O'Farrell P. Nitric oxide-induced suspended animation promotes survival during hypoxia. EMBO J. 2003 Feb 03; 22(3):580-7. PMID: 12554658; PMCID: PMC140754.
    43. Foley E, O'Farrell P. Nitric oxide contributes to induction of innate immune responses to gram-negative bacteria in Drosophila. Genes Dev. 2003 Jan 01; 17(1):115-25. PMID: 12514104; PMCID: PMC195964.
    44. Vidwans SJ, Wong ML, O'Farrell P. Anomalous centriole configurations are detected in Drosophila wing disc cells upon Cdk1 inactivation. J Cell Sci. 2003 Jan 01; 116(Pt 1):137-43. PMID: 12456723; PMCID: PMC2754245.
    45. Vidwans SJ, DiGregorio PJ, Shermoen AW, Foat B, Iwasa J, Yakubovich N, O'Farrell P. Sister chromatids fail to separate during an induced endoreplication cycle in Drosophila embryos. Curr Biol. 2002 May 14; 12(10):829-33. PMID: 12015119; PMCID: PMC2754250.
    46. O'Farrell P. Triggering the all-or-nothing switch into mitosis. Trends Cell Biol. 2001 Dec; 11(12):512-9. PMID: 11719058; PMCID: PMC2765372.
    47. O'Farrell P. Conserved responses to oxygen deprivation. J Clin Invest. 2001 Mar; 107(6):671-4. PMID: 11254666; PMCID: PMC208955.
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