DRSC: Completed Screens By Topic

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DRSC >> Screens >> Completed Screens By Topic

Screens for genes relevant to chromosome pairing

Bateman JR, Larschan E, D'Souza R, Marshall LS, Dempsey KE, Johnson JE, Mellone BG, Kuroda MI. A Genome-Wide Screen Identifies Genes That Affect Somatic Homolog Pairing in Drosophila. G3 July 1, 2012 vol. 2 no. 7 731-740.

Joyce EF, Williams BR, Xie T, Wu CT. Identification of Genes That Promote or Antagonize Somatic Homolog Pairing Using a High-Throughput FISH-Based Screen. PLoS Genet. 2012 May;8(5):e1002667. Epub 2012 May 10.

Screens in Primary Cells

Schulte J, Sepp KJ, Wu C, Hong P, Littleton JT. High-Content Chemical and RNAi Screens for Suppressors of Neurotoxicity in a Huntington's Disease Model. PLoS ONE 2011;6(8):e23841. Epub 2011 Aug 31.

Perrimon N, Zirin J, Bai J. Primary Cell Cultures from Drosophila Gastrula Embryos. J Vis Exp. 2011 Feb 28;(48). pii: 2215. doi: 10.3791/2215.

Wu C, Schulte J, Sepp KJ, Littleton JT, Hong P. Automatic robust neurite detection and morphological analysis of neuronal cell cultures in high-content screening. Neuroinformatics. 2010 Jun;8(2):83-100.

Sepp KJ, Hong P, Lizarraga SB, Liu JS, Mejia LA, Walsh CA, Perrimon N. Identification of neural outgrowth genes using genome-wide RNAi. PLoS Genet 2008 Jul 4;4(7):e1000111.

Bai J, Binari R, Ni JQ, Vijayakanthan M, Li HS, Perrimon N. RNA interference screening in Drosophila primary cells for genes involved in muscle assembly and maintenance. Development. 2008 Apr;135(8):1439-49.

Screens for genes relevant to Cell Viability, Metabolism and Cell Death

Kondo S, Perrimon N. A Genome-Wide RNAi Screen Identifies Core Components of the G2-M DNA Damage Checkpoint. Sci. Signal. 2011 Jan 4. Vol. 4, Issue 154, p. rs1

Ravi D, Wiles AM, Bhavani S, Ruan J, Leder P, Bishop AJ. A network of conserved damage survival pathways revealed by a genomic RNAi screen. PLoS Genet 2009 Jun;5(6) Correction

Kwon M, Godinho SA, Chandhok NS, Ganem NJ, Azioune A, Thery M, Pellman D. Mechanisms to suppress multipolar divisions in cancer cells with extra centrosomes. Genes Dev. 2008 Aug 15;22(16):2189-203. Epub 2008 Jul 28.

Farny NG, Hurt JA, Silver PA. Definition of global and transcript-specific mRNA export pathways in metazoans. Genes Dev. 2008 Jan 1;22(1):66-78.

Yi CH, Sogah DK, Boyce M, Degterev A, Christofferson DE, Yuan J. A genome-wide RNAi screen reveals multiple regulators of caspase activation. J Cell Biol. 2007 Nov 19;179(4):619-26.

Screens for genes relevant to Transcription, Translation & RNA Biology

DRSC Reagents screened at the NYU RNAi Core: Imberg-Kazdan K, Ha S, Greenfield A, Poultney CS, Bonneau R, Logan SK, Garabedian MJ. A genome-wide RNA interference screen identifies new regulators of androgen receptor function in prostate cancer cells. Genome Res. 2013 Apr;23(4):581-91. doi: 10.1101/gr.144774.112. Epub 2013 Feb 12.

Stender JD, Pascual G, Liu W, Kaikkonen MU, Do K, Spann NJ, Boutros M, Perrimon N, Rosenfeld MG, Glass CK. Control of Proinflammatory Gene Programs by Regulated Trimethylation and Demethylation of Histone H4K20. Molecular Cell, 23 August 2012, 10.1016/j.molcel.2012.07.020.

Larschan E, Soruco MM, Lee OK, Peng S, Bishop E, Chery J, Goebel K, Feng J, Park PJ, Kuroda MI. Identification of Chromatin-Associated Regulators of MSL Complex Targeting in Drosophila Dosage Compensation. PLoS Genet. 2012 Jul;8(7):e1002830. Epub 2012 Jul 26.

Grimberg KB, Beskow A, Lundin D, Davis MM, Young P. Basic-Leucine Zipper Protein Cnc-C is a Substrate and Transcriptional Regulator of the Drosophila 26S Proteasome. Mol Cell Biol. 2011 Feb;31(4):897-909. Epub 2010 Dec 13.

Mourikis P, Lake RJ, Firnhaber CB, Dedecker BS. Modifiers of notch transcriptional activity identified by genome-wide RNAi. BMC Dev Biol. 2010 Oct 19;10(1):107.

Dekanty A, Romero NM, Bertolin AP, Thomas MG, Leishman CC, Perez-Perri JI, Boccaccio GL, Wappner P. Drosophila genome-wide RNAi screen identifies multiple regulators of HIF-dependent transcription in hypoxia. PLoS Genet. 2010 Jun 24;6(6):e1000994.

Zhou R, Hotta I, Denli AM, Hong P, Perrimon N, Hannon GJ. Comparative Analysis of Argonaute-Dependent Small RNA Pathways in Drosophila, Molecular Cell, Volume 32, Issue 4, 21 November 2008, Pages 592-599.

Wagner EJ, Burch BD, Godfrey AC, Salzler HR, Duronio RJ, Marzluff WF. A genome-wide RNA interference screen reveals that variant histones are necessary for replication-dependent histone pre-mRNA processing. Mol Cell. 2007 Nov 30;28(4):692-9.

Lu J, Ruhf ML, Perrimon N, Leder P. A genome-wide RNA interference screen identifies putative chromatin regulators essential for E2F repression. Proc Natl Acad Sci U S A. 2007 May 29;104(22):9381-6.

Cherry S, Doukas T, Armknecht S, Whelan S, Wang H, Sarnow P, Perrimon N. Genome-wide RNAi screen reveals a specific sensitivity of IRES-containing RNA viruses to host translation inhibition. Genes Dev. 2005 Feb 15;19(4):445-52.

Screens for genes relevant to Response to Pathogen Infection

Moser TS, Jones RG, Thompson CB, Coyne CB, Cherry S. A kinome RNAi screen identified AMPK as promoting poxvirus entry through the control of actin dynamics. PLoS Pathog. 2010 Jun 17;6(6):e1000954.

Akimana C, Al-Khodor S, Abu Kwaik Y. Host Factors Required for Modulation of Phagosome Biogenesis and Proliferation of Francisella tularensis within the Cytosol. PLoS One. 2010 Jun 11;5(6):e11025.

Sessions OM, Barrows NJ, Souza-Neto JA, Robinson TJ, Hershey CL, Rodgers MA, Ramirez JL, Dimopoulos G, Yang PL, Pearson JL, Garcia-Blanco MA. Discovery of insect and human dengue virus host factors. Nature 2009 Apr 23; 485; 1047-50.

Philips JA, Porto MC, Wang H, Rubin EJ, Perrimon N. ESCRT factors restrict mycobacterial growth. Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):3070-5.

Derré I, Pypaert M, Dautry-Varsat A, Agaisse H. RNAi screen in Drosophila cells reveals the involvement of the Tom complex in Chlamydia infection. PLoS Pathog. 2007 Oct 26;3(10):1446-58.

Agaisse H, Burrack LS, Philips JA, Rubin EJ, Perrimon N, Higgins DE. Genome-wide RNAi screen for host factors required for intracellular bacterial infection. Science. 2005 Aug 19;309(5738):1248-51.

Philips JA, Rubin EJ, Perrimon N. Drosophila RNAi screen reveals CD36 family member required for mycobacterial infection. Science. 2005 Aug 19;309(5738):1251-3.

Cherry S, Kunte A, Wang H, Coyne C, Rawson RB, Perrimon N. COPI activity coupled with fatty acid biosynthesis is required for viral replication. PLoS Pathog. 2006 Oct;2(10):e102.

Screens for genes relevant to Neurobiology and Neurodegenerative Disease

Zhang S, Binari R, Zhou R, Perrimon N. A genomewide RNA interference screen for modifiers of aggregates formation by mutant Huntingtin in Drosophila. Genetics. 2010 Apr;184(4):1165-79. Epub 2010 Jan 25.

Sepp KJ, Hong P, Lizarraga SB, Liu JS, Mejia LA, Walsh CA, Perrimon N. Identification of neural outgrowth genes using genome-wide RNAi. PLoS Genet 2008 Jul 4;4(7):e1000111.

Screens for genes relevant to Signal Transduction

Bergwitz C, Wee MJ, Sinha S, Huang J, DeRobertis C, Mensah LB, Cohen J, Friedman A, Kulkarni M, Hu Y, Vinayagam A, Schnall-Levin M, Berger B, Perkins LA, Mohr SE, Perrimon N. Genetic Determinants of Phosphate Response in Drosophila. PLoS ONE 2013;8(3):e56753. doi: 10.1371/journal.pone.0056753. Epub 2013 Mar 8.

Aikin R, Cervantes A, D'Angelo G, Ruel L, Lacas-Gervais S, Schaub S, Thérond P. A Genome-Wide RNAi Screen Identifies Regulators of Cholesterol-Modified Hedgehog Secretion in Drosophila. PLoS One. 2012;7(3):e33665. Epub 2012 Mar 14.

Friedman A, Tucker G, Singh R, Yan D, Vinayagam A, Hu Y, Binari R, Hong P, Sun X, Porto M, Pacifico S, Murali T, Finley R, Asara JM, Berger B, Perrimon N. Proteomic and functional genomic landscape of receptor tyrosine kinase and Ras to extracellular signal-regulated kinase signaling. Science Signaling. 2011 Oct 25;4(196):rs10.

Port F, Hausmann G, Basler K. A genome-wide RNA interference screen uncovers two p24 proteins as regulators of Wingless secretion. EMBO Rep. 2011, doi: 10.1038/embor.2011.165.

Booker M, Samsonova AA, Kwon Y, Flockhart I, Mohr SE, Perrimon N. False negative rates in Drosophila cell-based RNAi screens: A case study. BMC Genomics 2011, 12:50doi:10.1186/1471-2164-12-50.

Kondo S, Perrimon N. A Genome-Wide RNAi Screen Identifies Core Components of the G2-M DNA Damage Checkpoint. Sci. Signal. 2011 Jan 4. Vol. 4, Issue 154, p. rs1

Mourikis P, Lake RJ, Firnhaber CB, Dedecker BS. Modifiers of notch transcriptional activity identified by genome-wide RNAi. BMC Dev Biol. 2010 Oct 19;10(1):107.

Kockel L, Kerr KS, Melnick M, Brückner K, Hebrok M, Perrimon N. Dynamic Switch of Negative Feedback Regulation in Drosophila Akt-TOR Signaling. PLoS Genet 2010 Jun 17;6(6):e1000990.

Nir O, Bakal C, Perrimon N, Berger B. Inference of RhoGAP/GTPase regulation using single-cell morphological data from a combinatorial RNAi screen. Genome Research. Mar;20(3):372-80. Epub 2010 Feb 9.

Bakal C, Linding R, Llense F, Heffern E, Martin-Blanco E, Pawson T, Perrimon N. Phosphorylation networks regulating JNK activity in diverse genetic backgrounds. Science 2008 Oct 17;322(5900):453-6.

Sathyanarayanan S, Zheng X, Kumar S, Chen CH, Chen D, Hay B, Sehgal A. Identification of novel genes involved in light-dependent CRY degradation through a genome-wide RNAi screen. Genes Dev. 2008 Jun 1;22(11):1522-33.

Wang J, Zhou X, Bradley PL, Chang SF, Perrimon N, Wong ST. Cellular phenotype recognition for high-content RNA interference genome-wide screening. J Biomol Screen. 2008 Feb;13(1):29-39.

Xu L, Yao X, Chen X, Lu P, Zhang B, Ip YT. Msk is required for nuclear import of TGF-{beta}/BMP-activated Smads. J Cell Biol. 2007 Sep 10;178(6):981-94.

Bakal C, Aach J, Church G, Perrimon N. Quantitative morphological signatures define local signaling networks regulating cell morphology. Science. 2007 Jun 22;316(5832):1753-6.

Gwack Y, Srikanth S, Feske S, Cruz-Guilloty F, Oh-hora M, Neems DS, Hogan PG, Rao A. Biochemical and functional characterization of Orai proteins. J Biol Chem. 2007 Jun 1;282(22):16232-43. Epub 2007 Feb 9.

Friedman A, Perrimon N. A functional RNAi screen for regulators of receptor tyrosine kinase and ERK signalling. Nature. 2006 Nov 9;444(7116):230-4.

Zhang SL, Yeromin AV, Zhang XH, Yu Y, Safrina O, Penna A, Roos J, Stauderman KA, Cahalan MD. Genome-wide RNAi screen of Ca(2+) influx identifies genes that regulate Ca(2+) release-activated Ca(2+) channel activity. Proc Natl Acad Sci U S A. 2006 Jun 13;103(24):9357-62.

Gwack Y, Sharma S, Nardone J, Tanasa B, Iuga A, Srikanth S, Okamura H, Bolton D, Feske S, Hogan PG, Rao A. A genome-wide Drosophila RNAi screen identifies DYRK-family kinases as regulators of NFAT. Nature. 2006 Jun 1;441(7093):646-50.

Vig M, Peinelt C, Beck A, Koomoa DL, Rabah D, Koblan-Huberson M, Kraft S, Turner H, Fleig A, Penner R, Kinet JP. CRACM1 is a plasma membrane protein essential for store-operated Ca2+ entry. Science. 2006 May 26;312(5777):1220-3.

Feske S, Gwack Y, Prakriya M, Srikanth S, Puppel SH, Tanasa B, Hogan PG, Lewis RS, Daly M, Rao A. A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function. Nature. 2006 May 11;441(7090):179-85

Nybakken K, Vokes SA, Lin TY, McMahon AP, Perrimon N. A genome-wide RNA interference screen in Drosophila melanogaster cells for new components of the Hh signaling pathway. Nat Genet. 2005 Dec;37(12):1323-32.

Baeg GH, Zhou R, Perrimon N. Genome-wide RNAi analysis of JAK/STAT signaling components in Drosophila. Genes Dev. 2005 Aug 15;19(16):1861-70.

DasGupta R, Kaykas A, Moon RT, Perrimon N. Functional genomic analysis of the Wnt-wingless signaling pathway. Science. 2005 May 6;308(5723):826-33.

Screens for genes relevant to Import/Export, Influx/Efflux and Transport

Stotz SC, Clapham DE. Anion-sensitive fluorophore identifies the Drosophila swell-activated chloride channel in a genome-wide RNA interference screen. PLoS One. 2012;7(10):e46865. doi: 10.1371/journal.pone.0046865. Epub 2012 Oct 4.

Port F, Hausmann G, Basler K. A genome-wide RNA interference screen uncovers two p24 proteins as regulators of Wingless secretion. EMBO Rep. 2011, doi: 10.1038/embor.2011.165.

Wendler F, Gillingham AK, Sinka R, Rosa-Ferreira C, Gordon DE, Franch-Marro X, Peden AA, Vincent JP, Munro S. A genome-wide RNA interference screen identifies two novel components of the metazoan secretory pathway. EMBO J. 2010 Jan 20;29(2):304-14. Epub 2009 Nov 26.

Jiang D, Zhao L, Clapham DE. Genome-wide RNAi screen identifies Letm1 as a mitochondrial Ca2+/H+ antiporter. Science. 2009 Oct 2;326(5949):144-7.

Cuttell L, Vaughan A, Silva E, Escaron CJ, Lavine M, Van Goethem E, Eid JP, Quirin M, Franc NC. Undertaker, a Drosophila Junctophilin, links Draper-mediated phagocytosis and calcium homeostasis. Cell. 2008 Oct 31;135(3):524-34.

Xu L, Yao X, Chen X, Lu P, Zhang B, Ip YT. Msk is required for nuclear import of TGF-{beta}/BMP-activated Smads. J Cell Biol. 2007 Sep 10;178(6):981-94.

Bard F, Casano L, Mallabiabarrena A, Wallace E, Saito K, Kitayama H, Guizzunti G, Hu Y, Wendler F, Dasgupta R, Perrimon N, Malhotra V. Functional genomics reveals genes involved in protein secretion and Golgi organization. Nature. 2006 Feb 2;439(7076):604-7.

Screens for genes relevant to Cell Division, Morphology and the Cytoskeleton

Rohn JL, Sims D, Liu T, Fedorova M, Schoeck F, Dopie J, Vartiainen M, Kiger AA, Perrimon N, Baum B. Comparative RNAi screening identifies a conserved core metazoan actinome by phenotype. J. Cell Biol. 2011, 194. 789-805.

Erhardt S, Mellone BG, Betts CM, Zhang W, Karpen GH, Straight AF. Genome-wide analysis reveals a cell cycle-dependent mechanism controlling centromere propagation. J Cell Biol. 2008 Dec 1;183(5):805-18.

Sims D, Duchek P, Baum B. PDGF/VEGF signalling controls cell size in Drosophila. Genome Biol. 2009 Feb 12;10(2):R20.

Sepp KJ, Hong P, Lizarraga SB, Liu JS, Mejia LA, Walsh CA, Perrimon N. Identification of neural outgrowth genes using genome-wide RNAi. PLoS Genet 2008 Jul 4;4(7):e1000111.

Eggert US, Kiger AA, Richter C, Perlman ZE, Perrimon N, Mitchison TJ, Field CM. Parallel chemical genetic and genome-wide RNAi screens identify cytokinesis inhibitors and targets. PLoS Biol. 2004 Dec;2(12):e379.

Boutros M, Kiger AA, Armknecht S, Kerr K, Hild M, Koch B, Haas SA, Paro R, Perrimon N; Heidelberg Fly Array Consortium. Genome-wide RNAi analysis of growth and viability in Drosophila cells. Science. 2004 Feb 6;303(5659):832-5.

Kiger AA, Baum B, Jones S, Jones MR, Coulson A, Echeverri C, Perrimon N. A functional genomic analysis of cell morphology using RNA interference. J Biol. 2003;2(4):27.

Screens for Genes Relevant to Organelle Formation, Fission/Fusion and Function

Jiang D, Zhao L, Clapham DE. Genome-wide RNAi screen identifies Letm1 as a mitochondrial Ca2+/H+ antiporter. Science. 2009 Oct 2;326(5949):144-7.

Beller M, Sztalryd C, Southall N, Bell M, Jäckle H, Auld DS, Oliver B. COPI Complex Is a Regulator of Lipid Homeostasis. PLoS Biology 2008 Nov 25;6(11):e292.

Gandre-Babbe S and van der Bliek AM. The Novel Tail-anchored Membrane Protein Mff Controls Mitochondrial and Peroxisomal Fission in Mammalian Cells. Mol Biol Cell 2008 Jun;19(6):2402-12. Epub 2008 Mar 19.

Screens Relevant to Circadian Rhythms

Screens Performed at NYU with DRSC Libraries

Bioinformatics and Data Analysis based on Screens done at DRSC

Booker M, Samsonova AA, Kwon Y, Flockhart I, Mohr SE, Perrimon N. False negative rates in Drosophila cell-based RNAi screens: A case study. BMC Genomics 2011, 12:50doi:10.1186/1471-2164-12-50.

Wiles AM, Doderer M, Ruan J, Gu TT, Ravi D, Blackman B, Bishop AJ. Building and analyzing protein interactome networks by cross-species comparisons. BMC Syst Biol. 2010 Mar 30;4(1):36.

Kaplow IM, Singh R, Friedman A, Bakal C, Perrimon N, Berger B. RNAiCut: automated detection of significant genes from functional genomic screens. Nat Methods. 2009 Jul;6(7):476-7.

Ravi D, Wiles AM, Bhavani S, Ruan J, Leder P, Bishop AJ. A network of conserved damage survival pathways revealed by a genomic RNAi screen. PLoS Genet 2009 Jun;5(6) Correction

Wiles AM, Ravi D, Bhavani S, Bishop AJ. An Analysis of Normalization Methods for Drosophila RNAi Genomic Screens and Development of a Robust Validation Scheme. J Biomol Screen. 2008 Sep;13(8):777-84. Epub 2008 Aug 27.

Drosophila RNAi Methodology & Protocols

Perrimon N, Zirin J, Bai J. Primary Cell Cultures from Drosophila Gastrula Embryos. J Vis Exp. 2011 Feb 28;(48). pii: 2215. doi: 10.3791/2215.

Mohr S, Bakal C, Perrimon N. Genomic Screening with RNAi: Results and Challenges. Annu Rev Biochem. 2010;79:37-64.

Bai J, Sepp KJ, Perrimon N. Culture of Drosophila primary cells dissociated from gastrula embryos and their use in RNAi screening. Nat Protoc. 2009;4(10):1502-12. Epub 2009 Sep 24.

Wang J, Zhou X, Bradley PL, Chang SF, Perrimon N, Wong ST. Cellular phenotype recognition for high-content RNA interference genome-wide screening. J Biomol Screen. 2008 Feb;13(1):29-39.

Ni JQ, Markstein M, Binari R, Pfeiffer B, Liu LP, Villalta C, Booker M, Perkins L, Perrimon N. Vector and parameters for targeted transgenic RNA interference in Drosophila melanogaster. Nat Methods. 2008 Jan;5(1):49-51.

DasGupta R, Nybakken K, Booker M, Mathey-Prevot B, Gonsalves F, Changkakoty B,Perrimon N. A case study of the reproducibility of transcriptional reporter cell-based RNAi screens in Drosophila. Genome Biol. 2007;8(9):R203.

Ramadan N, Flockhart I, Booker M, Perrimon N, Mathey-Prevot B. Design and implementation of high-throughput RNAi screens in cultured Drosophila cells. Nat Protoc. 2007;2(9):2245-64.

Perrimon N, Mathey-Prevot B. Applications of high-throughput RNA interference screens to problems in cell and developmental biology. Genetics. 2007 Jan;175(1):7-16.

Echeverri CJ, Perrimon N. High-throughput RNAi screening in cultured cells: a user's guide. Nat Rev Genet. 2006 May;7(5):373-84.

Armknecht S, Boutros M, Kiger A, Nybakken K, Mathey-Prevot B, Perrimon N. High-throughput RNA interference screens in Drosophila tissue culture cells. Methods Enzymol. 2005;392:55-73.

Off-Target Effects in Drosophila RNAi

Booker M, Samsonova AA, Kwon Y, Flockhart I, Mohr SE, Perrimon N. False negative rates in Drosophila cell-based RNAi screens: A case study. BMC Genomics 2011, 12:50doi:10.1186/1471-2164-12-50.

Kulkarni MM, Booker M, Silver SJ, Friedman A, Hong P, Perrimon N, Mathey-Prevot B. Evidence of off-target effects associated with long dsRNAs in Drosophila melanogaster cell-based assays. Nat Methods. 2006 Oct;3(10):833-8.

The DRSC Database & Software Tools

Vinayagam A, Hu Y, Kulkarni M, Roesel C, Sopko R, Mohr SE, Perrimon N. Protein complex-based analysis framework for high-throughput data sets. Sci Signal. 2013 Feb 26;6(264):rs5. doi: 10.1126/scisignal.2003629.

Hu Y, Flockhart I, Vinayagam A, Bergwitz C, Berger B, Perrimon N, Mohr SE. An Integrative Approach to Ortholog Prediction for Disease-Focused and Other Functional Studies. BMC Bioinformatics. 2011 Aug 31;12(1):357.

Flockhart I, Booker M, Kiger A, Boutros M, Armknecht S, Ramadan N, Richardson K, Xu A, Perrimon N, Mathey-Prevot B. FlyRNAi: the Drosophila RNAi screening center database. Nucleic Acids Res. 2006 Jan 1;34(Database issue):D489-94

DRSC Reviews

Mohr SE, Perrimon N. RNAi screening: new approaches, understandings, and organisms. Wiley Interdiscip Rev RNA. 2011 Sep 22. doi: 10.1002/wrna.110. [Epub ahead of print]

Neumüller RA, Perrimon N. Where gene discovery turns into systems biology: genome-scale RNAi screens in Drosophila. Wiley Interdiscip Rev Syst Biol Med. 2011 Jul-Aug;3(4):471-8. doi: 10.1002/wsbm.127. Epub 2010 Dec 31.

Perrimon N, Ni JQ, Perkins L. In vivo RNAi: Today and Tomorrow. Cold Spring Harb Perspect Biol. 2010 Aug 1;2(8):a003640. Epub 2010 Jun 9.

Mohr S, Bakal C, Perrimon N. Genomic Screening with RNAi: Results and Challenges. Annu Rev Biochem. 2010;79:37-64.