The National Institute of Diabetes & Digestive & Kidney Diseases

Subtle perturbations in networks are likely to cause much of inherited disease susceptibility, but understanding how complex genotypes and environmental interactions result in disease will require experimental systems biology in model organisms. Predictive models for gene and pathway function will be important for diagnosis and ultimately intervention, fulfilling the promise of the human genome project.

The humble fruit fly, Drosophila melanogaster, is an important model system, boasting facile genetics, complex organ systems, complex behaviors and a sequenced genome. Fruit flies are easy to propagate and require little lab space. Our long-term goal is to develop predictive models of gene function based on gene network analysis in Fruit flies. Intermediate problems within the community of scientists working on Fruit flies are identifying all genes, mRNA isoforms and regulatory elements encoded in the genome, determining genetic function genome-wide, and developing connectivity maps.

Our approach relies on a combination of high-throughput techniques to profile biological processes such as expression, promoter occupancy, and chromatin status in conjunction with computational analysis of genomic sequence. Along the way we are addressing a number of interesting questions highly amenable to genome wide analysis. For example, lipid storage and the transcriptional response to altered gene copy number.

Malone JH, Cho DY, Mattiuzzo NR, Artieri CG, Jiang L, Dale RK, Smith HE, McDaniel J, Munro S, Salit M, Andrews J, Przytycka TM, Oliver B.Mediation of Drosophila autosomal dosage effects and compensation by network interactions.Genome Biol.2012 Apr 24;13(4):R28. [Epub ahead of print] [Full Text/Abstract]

Deng X, Hiatt JB, Nguyen DK, Ercan S, Sturgill D, Hillier LW, Schlesinger F, Davis CA, Reinke VJ, Gingeras TR, Shendure J, Waterston RH, Oliver B, Lieb JD, Disteche CM.Evidence for compensatory upregulation of expressed X-linked genes in mammals, Caenorhabditis elegans and Drosophila melanogaster. Nat Genet. 2011 Oct 23;43(12):1179-85. doi: 10.1038/ng.948. [Full Text/Abstract]

Jiang L, Schlesinger F, Davis CA, Zhang Y, Li R, Salit M, Gingeras TR, Oliver B. Synthetic spike-in standards for RNA-seq experiments.Genome Res. 2011 Sep;21(9):1543-51. Epub 2011 Aug 4. [Full Text/Abstract]

Parisi M, Li R, Oliver B. Lipid profiles of female and male Drosophila. BMC Res Notes. 2011 Jun 15;4:198. [Full Text/Abstract]

Malone JH, Oliver B. Microarrays, deep sequencing and the true measure of the transcriptome. BMC Biol. 2011 May 31;9:34. Review. [Full Text/Abstract]

Graveley BR, Brooks AN, Carlson JW, Duff MO, Landolin JM, Yang L, Artieri CG, van Baren MJ, Boley N, Booth BW, Brown JB, Cherbas L, Davis CA, Dobin A, Li R, Lin W, Malone JH, Mattiuzzo NR, Miller D, Sturgill D, Tuch BB, Zaleski C, Zhang D, Blanchette M, Dudoit S, Eads B, Green RE, Hammonds A, Jiang L, Kapranov P, Langton L, Perrimon N, Sandler JE, Wan KH, Willingham A, Zhang Y, Zou Y, Andrews J, Bickel PJ, Brenner SE, Brent MR, Cherbas P, Gingeras TR, Hoskins RA, Kaufman TC, Oliver B, Celniker SE. The developmental transcriptome of Drosophila melanogaster. Nature. 2011 Mar 24;471(7339):473-9. Epub 2010 Dec 22. [Full Text/Abstract]

modENCODE Consortium, Roy S, Ernst J, Kharchenko PV, Kheradpour P, Negre N, Eaton ML, Landolin JM, Bristow CA, Ma L, Lin MF, Washietl S, Arshinoff BI, Ay F, Meyer PE, Robine N, Washington NL, Di Stefano L, Berezikov E, Brown CD, Candeias R, Carlson JW, Carr A, Jungreis I, Marbach D, Sealfon R, Tolstorukov MY, Will S, Alekseyenko AA, Artieri C, Booth BW, Brooks AN, Dai Q, Davis CA, Duff MO, Feng X, Gorchakov AA, Gu T, Henikoff JG, Kapranov P, Li R, MacAlpine HK, Malone J, Minoda A, Nordman J, Okamura K, Perry M, Powell SK, Riddle NC, Sakai A, Samsonova A, Sandler JE, Schwartz YB, Sher N, Spokony R, Sturgill D, van Baren M, Wan KH, Yang L, Yu C, Feingold E, Good P, Guyer M, Lowdon R, Ahmad K, Andrews J, Berger B, Brenner SE, Brent MR, Cherbas L, Elgin SC, Gingeras TR, Grossman R, Hoskins RA, Kaufman TC, Kent W, Kuroda MI, Orr-Weaver T, Perrimon N, Pirrotta V, Posakony JW, Ren B, Russell S, Cherbas P, Graveley BR, Lewis S, Micklem G, Oliver B, Park PJ, Celniker SE, Henikoff S, Karpen GH, Lai EC, MacAlpine DM, Stein LD, White KP, Kellis M.Identification of functional elements and regulatory circuits by Drosophila modENCODE.Science. 2010 Dec 24;330(6012):1787-97. Epub 2010 Dec 22.[Full Text/Abstract]

Parisi MJ, Gupta V, Sturgill D, Warren JT, Jallon JM, Malone JH, Zhang Y, Gilbert LI, Oliver B. Germline-dependent gene expression in distant non-gonadal somatic tissues of Drosophila. BMC Genomics. 2010 Jun 1;11:346.[Full Text/Abstract ]

Zhang Y, Malone JH, Powell SK, Periwal V, Spana E, Macalpine DM, Oliver B. Expression in aneuploid Drosophila S2 cells.PLoS Biol. 2010 Feb 23;8(2):e1000320.[Full Text/Abstract]

Zhang Y, Oliver B. An evolutionary consequence of dosage compensation on Drosophila melanogaster female X-chromatin structure? BMC Genomics. 2010 Jan 5;11:6. [Full Text/Abstract]

Malone J, Oliver B. The genomic 'inner fish' and a regulatory enigma in the vertebrates. J Biol. 2009;8(3):32. Epub 2009 Apr 16. Review. [Full Text/Abstract]

Beller M, Sztalryd C, Southall N, Bell M, Jäckle H, Auld DS, Oliver B. COPI complex is a regulator of lipid homeostasis. PLoS Biol. 2008 Nov 25;6(11):e292. [Full Text/Abstract]

Oliver B. Sex, dose, and equality. PLoS Biol. 2007 Dec;5(12):e340. No abstract available.

Sturgill D, Zhang Y, Parisi M, Oliver B. Demasculinization of X chromosomes in the Drosophila genus. Nature. 2007 Nov 8;450(7167):238-41. [Full Text/Abstract]

Zhang Y, Sturgill D, Parisi M, Kumar S, Oliver B. Constraint and turnover in sex-biased gene expression in the genus Drosophila. Nature. 2007 Nov 8;450(7167):233-7. [Full Text/Abstract]

Clark AG, Eisen MB, Smith DR, Bergman CM, Oliver B, Markow TA, Kaufman TC, Kellis M, Gelbart W, Iyer VN, Pollard DA, Sackton TB, Larracuente AM, Singh ND, Abad JP, Abt DN, Adryan B, Aguade M, Akashi H, Anderson WW, Aquadro CF, Ardell DH, Arguello R, Artieri CG, Barbash DA, Barker D, Barsanti P, Batterham P, Batzoglou S, Begun D, Bhutkar A, Blanco E, Bosak SA, Bradley RK, Brand AD, Brent MR, Brooks AN, Brown RH, Butlin RK, Caggese C, Calvi BR, Bernardo de Carvalho A, Caspi A, Castrezana S, Celniker SE, Chang JL, Chapple C, Chatterji S, Chinwalla A, Civetta A, Clifton SW, Comeron JM, Costello JC, Coyne JA, Daub J, David RG, Delcher AL, Delehaunty K, Do CB, Ebling H, Edwards K, Eickbush T, Evans JD, Filipski A, Findeiss S, Freyhult E, Fulton L, Fulton R, Garcia AC, Gardiner A, Garfield DA, Garvin BE, Gibson G, Gilbert D, Gnerre S, Godfrey J, Good R, Gotea V, Gravely B, Greenberg AJ, Griffiths-Jones S, Gross S, Guigo R, Gustafson EA, Haerty W, Hahn MW, Halligan DL, Halpern AL, Halter GM, Han MV, Heger A, Hillier L, Hinrichs AS, Holmes I, Hoskins RA, Hubisz MJ, Hultmark D, Huntley MA, Jaffe DB, Jagadeeshan S, Jeck WR, Johnson J, Jones CD, Jordan WC, Karpen GH, Kataoka E, Keightley PD, Kheradpour P, Kirkness EF, Koerich LB, Kristiansen K, Kudrna D, Kulathinal RJ, Kumar S, Kwok R, Lander E, Langley CH, Lapoint R, Lazzaro BP, Lee SJ, Levesque L, Li R, Lin CF, Lin MF, Lindblad-Toh K, Llopart A, Long M, Low L, Lozovsky E, Lu J, Luo M, Machado CA, Makalowski W, Marzo M, Matsuda M, Matzkin L, McAllister B, McBride CS, McKernan B, McKernan K, Mendez-Lago M, Minx P, Mollenhauer MU, Montooth K, Mount SM, Mu X, Myers E, Negre B, Newfeld S, Nielsen R, Noor MA, O'Grady P, Pachter L, Papaceit M, Parisi MJ, Parisi M, Parts L, Pedersen JS, Pesole G, Phillippy AM, Ponting CP, Pop M, Porcelli D, Powell JR, Prohaska S, Pruitt K, Puig M, Quesneville H, Ram KR, Rand D, Rasmussen MD, Reed LK, Reenan R, Reily A, Remington KA, Rieger TT, Ritchie MG, Robin C, Rogers YH, Rohde C, Rozas J, Rubenfield MJ, Ruiz A, Russo S, Salzberg SL, Sanchez-Gracia A, Saranga DJ, Sato H, Schaeffer SW, Schatz MC, Schlenke T, Schwartz R, Segarra C, Singh RS, Sirot L, Sirota M, Sisneros NB, Smith CD, Smith TF, Spieth J, Stage DE, Stark A, Stephan W, Strausberg RL, Strempel S, Sturgill D, Sutton G, Sutton GG, Tao W, Teichmann S, Tobari YN, Tomimura Y, Tsolas JM, Valente VL, Venter E, Venter JC, Vicario S, Vieira FG, Vilella AJ, Villasante A, Walenz B, Wang J, Wasserman M, Watts T, Wilson D, Wilson RK, Wing RA, Wolfner MF, Wong A, Wong GK, Wu CI, Wu G, Yamamoto D, Yang HP, Yang SP, Yorke JA, Yoshida K, Zdobnov E, Zhang P, Zhang Y, Zimin AV, Baldwin J, Abdouelleil A, Abdulkadir J, Abebe A, Abera B, Abreu J, Acer SC, Aftuck L, Alexander A, An P, Anderson E, Anderson S, Arachi H, Azer M, Bachantsang P, Barry A, Bayul T, Berlin A, Bessette D, Bloom T, Blye J, Boguslavskiy L, Bonnet C, Boukhgalter B, Bourzgui I, Brown A, Cahill P, Channer S, Cheshatsang Y, Chuda L, Citroen M, Collymore A, Cooke P, Costello M, D'Aco K, Daza R, De Haan G, DeGray S, DeMaso C, Dhargay N, Dooley K, Dooley E, Doricent M, Dorje P, Dorjee K, Dupes A, Elong R, Falk J, Farina A, Faro S, Ferguson D, Fisher S, Foley CD, Franke A, Friedrich D, Gadbois L, Gearin G, Gearin CR, Giannoukos G, Goode T, Graham J, Grandbois E, Grewal S, Gyaltsen K, Hafez N, Hagos B, Hall J, Henson C, Hollinger A, Honan T, Huard MD, Hughes L, Hurhula B, Husby ME, Kamat A, Kanga B, Kashin S, Khazanovich D, Kisner P, Lance K, Lara M, Lee W, Lennon N, Letendre F, LeVine R, Lipovsky A, Liu X, Liu J, Liu S, Lokyitsang T, Lokyitsang Y, Lubonja R, Lui A, MacDonald P, Magnisalis V, Maru K, Matthews C, McCusker W, McDonough S, Mehta T, Meldrim J, Meneus L, Mihai O, Mihalev A, Mihova T, Mittelman R, Mlenga V, Montmayeur A, Mulrain L, Navidi A, Naylor J, Negash T, Nguyen T, Nguyen N, Nicol R, Norbu C, Norbu N, Novod N, O'Neill B, Osman S, Markiewicz E, Oyono OL, Patti C, Phunkhang P, Pierre F, Priest M, Raghuraman S, Rege F, Reyes R, Rise C, Rogov P, Ross K, Ryan E, Settipalli S, Shea T, Sherpa N, Shi L, Shih D, Sparrow T, Spaulding J, Stalker J, Stange-Thomann N, Stavropoulos S, Stone C, Strader C, Tesfaye S, Thomson T, Thoulutsang Y, Thoulutsang D, Topham K, Topping I, Tsamla T, Vassiliev H, Vo A, Wangchuk T, Wangdi T, Weiand M, Wilkinson J, Wilson A, Yadav S, Young G, Yu Q, Zembek L, Zhong D, Zimmer A, Zwirko Z, Jaffe DB, Alvarez P, Brockman W, Butler J, Chin C, Gnerre S, Grabherr M, Kleber M, Mauceli E, MacCallum I.Evolution of genes and genomes on the Drosophila phylogeny. Drosophila 12 Genomes Consortium. Nature. 2007 Nov 8;450(7167):203-18. [Full Text/Abstract]

Hempel LU, Oliver B. Sex-specific DoublesexM expression in subsets of Drosophila somatic gonad cells. BMC Dev Biol. 2007 Oct 12;7:113. [Full Text/Abstract]

Zhang Y, Oliver B. Dosage compensation goes global. Curr Opin Genet Dev. 2007 Apr;17(2):113-20. Epub 2007 Feb 20. Review. [Full Text/Abstract]

Cerrato A, Parisi M, Santa Anna S, Missirlis F, Guru S, Agarwal S, Sturgill D, Talbot T, Spiegel A, Collins F, Chandrasekharappa S, Marx S, Oliver B. Genetic interactions between Drosophila melanogaster menin and Jun/Fos. Dev Biol. 2006 Oct 1;298(1):59-70. Epub 2006 Jun 10. [Full Text/Abstract]

FitzGerald PC, Sturgill D, Shyakhtenko A, Oliver B, Vinson C. Comparative genomics of Drosophila and human core promoters. Genome Biol. 2006;7(7):R53. [Full Text/Abstract]

Gupta V, Parisi M, Sturgill D, Nuttall R, Doctolero M, Dudko OK, Malley JD, Eastman PS, Oliver B. Global analysis of X-chromosome dosage compensation. J Biol. 2006;5(1):3. Epub 2006 Feb 16. [Full Text/Abstract]

Bielinska B, Lü J, Sturgill D, Oliver B. Core promoter sequences contribute to ovo-B regulation in the Drosophila melanogaster germline. Genetics. 2005 Jan;169(1):161-72. Epub 2004 Sep 15. [Full Text/Abstract]

Parisi M, Nuttall R, Edwards P, Minor J, Naiman D, Lü J, Doctolero M, Vainer M, Chan C, Malley J, Eastman S, Oliver B. A survey of ovary-, testis-, and soma-biased gene expression in Drosophila melanogaster adults. Genome Biol. 2004;5(6):R40. Epub 2004 Jun 1. [Full Text/Abstract]

Parisi M, Nuttall R, Naiman D, Bouffard G, Malley J, Andrews J, Eastman S, Oliver B. Paucity of genes on the Drosophila X chromosome showing male-biased expression. Science. 2003 Jan 31;299(5607):697-700. Epub 2003 Jan 2. [Full Text/Abstract]

Andrews J, Oliver B. Sex determination signals control ovo-B transcription in Drosophila melanogaster germ cells. Genetics. 2002 Feb;160(2):537-45. [Full Text/Abstract]

Oliver B. Genetic control of germline sexual dimorphism in Drosophila. Int Rev Cytol. 2002;219:1-60. Review. [Full Text/Abstract]

Lü J, Oliver B. Drosophila OVO regulates ovarian tumor transcription by binding unusually near the transcription start site. Development. 2001 May;128(9):1671-86. [Full Text/Abstract]

Andrews J, Bouffard GG, Cheadle C, Lü J, Becker KG, Oliver B. Gene discovery using computational and microarray analysis of transcription in the Drosophila melanogaster testis. Genome Res. 2000 Dec;10(12):2030-43. [Full Text/Abstract]

Andrews J, Garcia-Estefania D, Delon I, Lü J, Mével-Ninio M, Spierer A, Payre F, Pauli D, Oliver B. OVO transcription factors function antagonistically in the Drosophila female germline. Development. 2000 Feb;127(4):881-92. [Full Text/Abstract]

Oliver B, Singer J, Laget V, Pennetta G, Pauli D. Function of Drosophila ovo+ in germ-line sex determination depends on X-chromosome number. Development. 1994 Nov;120(11):3185-95. [Full Text/Abstract]

Oliver B, Perrimon N, Mahowald AP. Genetic evidence that the sans fille locus is involved in Drosophila sex determination. Genetics. 1988 Sep;120(1):159-71. [Full Text/Abstract]

Oliver B, Perrimon N, Mahowald AP. The ovo locus is required for sex-specific germ line maintenance in Drosophila. Genes Dev. 1987 Nov;1(9):913-23. [Full Text/Abstract]