Dr Cahir O'Kane University positionReader Dr Cahir O'Kane is pleased to consider applications from prospective PhD students. DepartmentsHome pagehttp://www.gen.cam.ac.uk/researc... (personal home page) Research ThemesInterestsWe are interested in the basic biology of axonal ER, and its relevance to neurodegenerative disease, using Drosophila as a model. Axonal ER forms a continuous tubular network throughout the neuron, comparable to a “neuron within a neuron”, potentially able to integrate physiological responses throughout the neuron. Is it important? Almost certainly - the motor axon degeneration disease, hereditary spastic paraplegia (HSP) results from mutations affecting several ER-shaping proteins. Using Drosophila, we have established roles for some HSP proteins in formation of axonal ER, by finding ER abnormalities in mutant axons, including occasional gaps in continuity. Current work includes development of screening tools to identify additional genes and mechanisms for formation of axonal ER, analyses of the ER network by light and EM, and the roles of ER in the physiology of axons and other organelles that contact ER. In addition, we are investigating roles of other HSP genes in autophagy.  Drosophila motor neuron terminals, showing exocytic active zones (green) surrounded by endocytic zones (magenta). Source: Y.P. Wairkar, I.M. Robinson and C.J. O'Kane Click image to view full-size Research Focus
EquipmentBehavioural analysis Calcium imaging Cell culture Confocal microscopy Drosophila genetics Electrophysiological recording techniques Fluorescence microscopy Immunohistochemistry Intracellular recording Microscopy Protein purification Recombinant protein expression Collaborators
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Key publicationsYalç?n B, Zhao L, Stofanko M, O’Sullivan NC, Roost A, Kang ZH, Thomas MR, Blard O, Zaessinger S, Patto AL, Sohail A,Baena V, Terasaki M, O’Kane CJ (2017), “Modeling of axonal endoplasmic reticulum network by spastic paraplegia proteins” eLife 6:e23882. DOI 10.7554/eLife.23882 O'Sullivan NC, Jahn TR, Reid E, O'Kane CJ (2012), “Reticulon-like-1, the Drosophila orthologue of the hereditary spastic paraplegia gene reticulon 2, is required for organization of endoplasmic reticulum and of distal motor axons.” Hum Mol Genet 21(15):3356-65 Details Blackstone C, O'Kane CJ, Reid E (2011), “Hereditary spastic paraplegias: membrane traffic and the motor pathway.” Nat Rev Neurosci 12(1):31-42 Details Rocha JJ, Korolchuk VI, Robinson IM, O'Kane CJ (2011), “A phagocytic route for uptake of double-stranded RNA in RNAi.” PLoS One 6(4):e19087 Details Wang X, Shaw WR, Tsang HT, Reid E, O'Kane CJ (2007), “Drosophila spichthyin inhibits BMP signaling and regulates synaptic growth and axonal microtubules.” Nat Neurosci 10(2):177-85 Details Razzaq A, Robinson IM, McMahon HT, Skepper JN, Su Y, Zelhof AC, Jackson AP, Gay NJ, O'Kane CJ (2001), “Amphiphysin is necessary for organization of the excitation-contraction coupling machinery of muscles, but not for synaptic vesicle endocytosis in Drosophila.” Genes Dev 15(22):2967-79 Details Publications2016Böhme MA, Beis C, Reddy-Alla S, Reynolds E, Mampell MM, Grasskamp AT, Lützkendorf J, Bergeron DD, Driller JH, Babikir H, Göttfert F, Robinson IM, O'Kane CJ, Hell SW, Wahl MC, Stelzl U, Loll B, Walter AM, Sigrist SJ (2016), “Active zone scaffolds differentially accumulate Unc13 isoforms to tune Ca2+ channel-synaptic vesicle coupling” Nat Neurosci 19:1311-20, doi: 10.1038/nn.4364 Pavel M, Imarisio S, Menzies, F Jimenez-Sanchez M, Siddiqi F, Wu X, Renna M, O'Kane CJ, Crowther DC, Rubinsztein DC (2016), “CCT complex restricts neuropathogenic protein aggregation via autophagy” Nat Comms 7:13821. Doi: 10.1038/ncomms13821 Yalç?n B, Zhao L, Stofanko M, O’Sullivan NC, Roost A, Kang ZH, Thomas MR, Blard O, Zaessinger S, Patto AL, Baena V, Terasaki M, O’Kane CJ (2016), “Modeling of axonal endoplasmic reticulum network by spastic paraplegia proteins (PREPRINT)” BioRxiv http://dx.doi.org/10.1101/069005 2015Jimenez-Sanchez M, Lam W, Hannus M, Sönnichsen B, Imarisio S, Fleming A, Tarditi A, Menzies F, Ed Dami T, Xu C, Gonzalez-Couto E, Lazzeroni G, Heitz F, Diamanti D, Massai L, Satagopam VP, Marconi G, Caramelli C, Nencini A, Andreini M, Sardone GL, Caradonna NP, Porcari V, Scali C, Schneider R, Pollio G, O'Kane CJ, Caricasole A, Rubinsztein DC (2015), “siRNA screen identifies QPCT as a druggable target for Huntington's disease” Nat Chem Biol 11: 347-354 Menzies FM, Garcia-Arencibia M, Imarisio S, O'Sullivan NC, Ricketts T, Kent BA, Rao MV, Lam W, Green-Thompson ZW, Nixon RA, Saksida LM, Bussey TJ, *O'Kane CJ, *Rubinsztein DC (2015), “Calpain inhibition mediates autophagy-dependent protection against polyglutamine toxicity” Cell Death Differ 22: 433-44 2014Masuda-Nakagawa LM, Ito K, Awasaki T, O'Kane CJ (2014), “A single GABAergic neuron mediates feedback of odor-evoked signals in the mushroom body of larval Drosophila.” Front Neural Circuits 8:35 Details Moreau K, Fleming A, Imarisio S, Lopez Ramirez A, Mercer JL, Jimenez-Sanchez M, Bento CF, Puri C, Zavodszky E, Siddiqi F, Lavau CP, Betton M, O'Kane CJ, Wechsler DS, Rubinsztein DC (2014), “PICALM modulates autophagy activity and tau accumulation” Nat Commun 5: 4998 2013Na D, Rouf M, O'Kane CJ, Rubinsztein DC, Gsponer J (2013), “NeuroGeM, a knowledgebase of genetic modifiers in neurodegenerative diseases.” BMC Med Genomics 6:52 Details O'Sullivan NC, Dräger N, O'Kane CJ (2013), “Characterization of the Drosophila atlastin interactome reveals VCP as a functionally related interactor.” J Genet Genomics 40(6):297-306 Details 2012Wardill TJ, List O, Li X, Dongre S, McCulloch M, Ting CY, O'Kane CJ, Tang S, Lee CH, Hardie RC, Juusola M (2012), “Multiple spectral inputs improve motion discrimination in the Drosophila visual system.” Science 336(6083):925-31 Details 2011Korolchuk VI, Saiki S, Lichtenberg M, Siddiqi FH, Roberts EA, Imarisio S, Jahreiss L, Sarkar S, Futter M, Menzies FM, O'Kane CJ, Deretic V, Rubinsztein DC (2011), “Lysosomal positioning coordinates cellular nutrient responses.” Nat Cell Biol 13(4):453-60 Details O'Kane CJ (2011), “Drosophila as a model organism for the study of neuropsychiatric disorders.” Curr Top Behav Neurosci 7:37-60 Details 2010Lone M, Kungl T, Koper A, Bottenberg W, Kammerer R, Klein M, Sweeney ST, Auburn RP, O'Kane CJ, Prokop A (2010), “The nuclear protein Waharan is required for endosomal-lysosomal trafficking in Drosophila.” J Cell Sci 123(Pt 14):2369-74 Details Masuda-Nakagawa LM, Awasaki T, Ito K, O'Kane CJ (2010), “Targeting expression to projection neurons that innervate specific mushroom body calyx and antennal lobe glomeruli in larval Drosophila.” Gene Expr Patterns 10(7-8):328-37 Details Underwood BR, Imarisio S, Fleming A, Rose C, Krishna G, Heard P, Quick M, Korolchuk VI, Renna M, Sarkar S, García-Arencibia M, O'Kane CJ, Murphy MP, Rubinsztein DC (2010), “Antioxidants can inhibit basal autophagy and enhance neurodegeneration in models of polyglutamine disease.” Hum Mol Genet 19(17):3413-29 Details Winslow AR, Chen CW, Corrochano S, Acevedo-Arozena A, Gordon DE, Peden AA, Lichtenberg M, Menzies FM, Ravikumar B, Imarisio S, Brown S, O'Kane CJ, Rubinsztein DC (2010), “?-Synuclein impairs macroautophagy: implications for Parkinson's disease.” J Cell Biol 190(6):1023-37 Details 2009Masuda-Nakagawa LM, Gendre N, O'Kane CJ, Stocker RF (2009), “Localized olfactory representation in mushroom bodies of Drosophila larvae.” Proc Natl Acad Sci U S A Details Nikolaev A, Zheng L, Wardill TJ, O'Kane CJ, de Polavieja GG, Juusola M (2009), “Network Adaptation Improves Temporal Representation of Naturalistic Stimuli in Drosophila Eye: II Mechanisms.” PLoS ONE 4(1):e4306 Details Raghu P, Coessens E, Manifava M, Georgiev P, Pettitt T, Wood E, Garcia-Murillas I, Okkenhaug H, Trivedi D, Zhang Q, Razzaq A, Zaid O, Wakelam M, O'Kane CJ, Ktistakis N (2009), “Rhabdomere biogenesis in Drosophila photoreceptors is acutely sensitive to phosphatidic acid levels.” J Cell Biol 185(1):129-45 Details Sharma P, Keane J, O'Kane CJ, Asztalos Z (2009), “Automated measurement of Drosophila jump reflex habituation and its use for mutant screening.” J Neurosci Methods 182(1):43-8 Details Tsang HT, Edwards TL, Wang X, Connell JW, Davies RJ, Durrington HJ, O'Kane CJ, Luzio JP, Reid E (2009), “The hereditary spastic paraplegia proteins NIPA1, spastin and spartin are inhibitors of mammalian BMP signalling.” Hum Mol Genet 18(20):3805-21 Details Zheng L, Nikolaev A, Wardill TJ, O'Kane CJ, de Polavieja GG, Juusola M (2009), “Network adaptation improves temporal representation of naturalistic stimuli in Drosophila eye: I dynamics.” PLoS ONE 4(1):e4307 Details 2008Ravikumar B, Imarisio S, Sarkar S, O'Kane CJ, Rubinsztein DC (2008), “Rab5 modulates aggregation and toxicity of mutant huntingtin through macroautophagy in cell and fly models of Huntington disease.” J Cell Sci 121(Pt 10):1649-60 Details Sarkar S, Krishna G, Imarisio S, Saiki S, O'Kane CJ, Rubinsztein DC (2008), “A rational mechanism for combination treatment of Huntington's disease using lithium and rapamycin.” Hum Mol Genet 17(2):170-8 Details Wang X, O'Kane CJ (2008), “Hereditary spastic paraplegia genes in Drosophila: dissecting their roles in axonal degeneration and intracellular traffic.” SEB Exp Biol Ser 60:161-82 Details Williams A, Sarkar S, Cuddon P, Ttofi EK, Saiki S, Siddiqi FH, Jahreiss L, Fleming A, Pask D, Goldsmith P, O'Kane CJ, Floto RA, Rubinsztein DC (2008), “Novel targets for Huntington's disease in an mTOR-independent autophagy pathway.” Nat Chem Biol 4(5):295-305 Details 2007Koh TW, Korolchuk VI, Wairkar YP, Jiao W, Evergren E, Pan H, Zhou Y, Venken KJ, Shupliakov O, Robinson IM, O'Kane CJ, Bellen HJ (2007), “Eps15 and Dap160 control synaptic vesicle membrane retrieval and synapse development.” J Cell Biol 178(2):309-22 Details Korolchuk VI, Schütz MM, Gómez-Llorente C, Rocha J, Lansu NR, Collins SM, Wairkar YP, Robinson IM, O'Kane CJ (2007), “Drosophila Vps35 function is necessary for normal endocytic trafficking and actin cytoskeleton organisation.” J Cell Sci 120(Pt 24):4367-76 Details Sarkar S, Perlstein EO, Imarisio S, Pineau S, Cordenier A, Maglathlin RL, Webster JA, Lewis TA, O'Kane CJ, Schreiber SL, Rubinsztein DC (2007), “Small molecules enhance autophagy and reduce toxicity in Huntington's disease models.” Nat Chem Biol 3(6):331-8 Details 2006Berger Z, Davies JE, Luo S, Pasco MY, Majoul I, O'Kane CJ, Rubinsztein DC (2006), “Deleterious and protective properties of an aggregate-prone protein with a polyalanine expansion.” Hum Mol Genet 15(3):453-65 Details Berger Z, Ravikumar B, Menzies FM, Oroz LG, Underwood BR, Pangalos MN, Schmitt I, Wullner U, Evert BO, O'Kane CJ, Rubinsztein DC (2006), “Rapamycin alleviates toxicity of different aggregate-prone proteins.” Hum Mol Genet 15(3):433-42 Details Ravikumar B, Berger Z, Vacher C, O'Kane CJ, Rubinsztein DC (2006), “Rapamycin pre-treatment protects against apoptosis.” Hum Mol Genet 15(7):1209-16 Details 2005Berger Z, Ttofi EK, Michel CH, Pasco MY, Tenant S, Rubinsztein DC, O'Kane CJ (2005), “Lithium rescues toxicity of aggregate-prone proteins in Drosophila by perturbing Wnt pathway.” Hum Mol Genet 14(20):3003-11 Details Gissen P, Johnson CA, Gentle D, Hurst LD, Doherty AJ, O'Kane CJ, Kelly DA, Maher ER (2005), “Comparative evolutionary analysis of VPS33 homologues: genetic and functional insights.” Hum Mol Genet 14(10):1261-70 Details Hodge JJ, Choi JC, O'Kane CJ, Griffith LC (2005), “Shaw potassium channel genes in Drosophila.” J Neurobiol 63(3):235-54 Details Masuda-Nakagawa LM, Tanaka NK, O'Kane CJ (2005), “Stereotypic and random patterns of connectivity in the larval mushroom body calyx of Drosophila.” Proc Natl Acad Sci U S A 102(52):19027-32 Details Sharma P, Asztalos Z, Ayyub C, de Bruyne M, Dornan AJ, Gomez-Hernandez A, Keane J, Killeen J, Kramer S, Madhavan M, Roe H, Sherkhane PD, Siddiqi K, Silva E, Carlson JR, Goodwin SF, Heisenberg M, Krishnan K, Kyriacou CP, Partridge L, Riesgo-Escovar J, Rodrigues V, Tully T, O'Kane CJ (2005), “Isogenic autosomes to be applied in optimal screening for novel mutants with viable phenotypes in Drosophila melanogaster.” J Neurogenet 19(2):57-85 Details 2004Liu H, Mardahl-Dumesnil M, Sweeney ST, O'Kane CJ, Bernstein SI (2004), “Drosophila paramyosin is important for myoblast fusion and essential for myofibril formation.” J Cell Biol 167(4):783 Details Mistry H, Wilson BA, Roberts IJ, O'Kane CJ, Skeath JB (2004), “Cullin-3 regulates pattern formation, external sensory organ development and cell survival during Drosophila development.” Mech Dev 121(12):1495-507 Details Ravikumar B, Vacher C, Berger Z, Davies JE, Luo S, Oroz LG, Scaravilli F, Easton DF, Duden R, O'Kane CJ, Rubinsztein DC (2004), “Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease.” Nat Genet 36(6):585-95 Details Ryder E, Blows F, Ashburner M, Bautista-Llacer R, Coulson D, Drummond J, Webster J, Gubb D, Gunton N, Johnson G, O'Kane CJ, Huen D, Sharma P, Asztalos Z, Baisch H, Schulze J, Kube M, Kittlaus K, Reuter G, Maroy P, Szidonya J, Rasmuson-Lestander A, Ekström K, Dickson B, Hugentobler C, Stocker H, Hafen E, Lepesant JA, Pflugfelder G, Heisenberg M, Mechler B, Serras F, Corominas M, Schneuwly S, Preat T, Roote J, Russell S (2004), “The DrosDel collection: a set of P-element insertions for generating custom chromosomal aberrations in Drosophila melanogaster.” Genetics 167(2):797-813 Details 2003O'Kane CJ (2003), “Modelling human diseases in Drosophila and Caenorhabditis.” Semin Cell Dev Biol 14(1):3-10 Details 2002Allen MJ, O'Kane CJ, Moffat KG (2002), “Cell ablation using wild-type and cold-sensitive ricin-A chain in Drosophila embryonic mesoderm.” Genesis 34(1-2):132-4 Details Bhattacharya S, Stewart BA, Niemeyer BA, Burgess RW, McCabe BD, Lin P, Boulianne G, O'Kane CJ, Schwarz TL (2002), “Members of the synaptobrevin/vesicle-associated membrane protein (VAMP) family in Drosophila are functionally interchangeable in vivo for neurotransmitter release and cell viability.” Proc Natl Acad Sci U S A 99(21):13867-72 Details Chan HY, Tung CK, O'Kane CJ (2002), “Rev-GFP transgenic lines for studies of nucleocytoplasmic transport in Drosophila.” Genesis 34(1-2):139-41 Details Keller A, Sweeney ST, Zars T, O'Kane CJ, Heisenberg M (2002), “Targeted expression of tetanus neurotoxin interferes with behavioral responses to sensory input in Drosophila.” J Neurobiol 50(3):221-33 Details 2001Bellaïche Y, Radovic A, Woods DF, Hough CD, Parmentier ML, O'Kane CJ, Bryant PJ, Schweisguth F (2001), “The Partner of Inscuteable/Discs-large complex is required to establish planar polarity during asymmetric cell division in Drosophila.” Cell 106(3):355-66 Details Chan HY, Brogna S, O'Kane CJ (2001), “Dribble, the Drosophila KRR1p homologue, is involved in rRNA processing.” Mol Biol Cell 12(5):1409-19 Details 2000Collier S, Chan HY, Toda T, McKimmie C, Johnson G, Adler PN, O'Kane C, Ashburner M (2000), “The Drosophila embargoed gene is required for larval progression and encodes the functional homolog of schizosaccharomyces Crm1.” Genetics 155(4):1799-807 Details Parmentier ML, Woods D, Greig S, Phan PG, Radovic A, Bryant P, O'Kane CJ (2000), “Rapsynoid/partner of inscuteable controls asymmetric division of larval neuroblasts in Drosophila.” J Neurosci 20(14):RC84 Details Razzaq A, Su Y, Mehren JE, Mizuguchi K, Jackson AP, Gay NJ, O'Kane CJ (2000), “Characterisation of the gene for Drosophila amphiphysin.” Gene 241(1):167-74 Details Wixon J, O'Kane C (2000), “Featured organism: Drosophila melanogaster.” Yeast 17(2):146-53 Details 1999Granderath S, Stollewerk A, Greig S, Goodman CS, O'Kane CJ, Klämbt C (1999), “loco encodes an RGS protein required for Drosophila glial differentiation.” Development 126(8):1781-91 Details Kiger JA Jr, Eklund JL, Younger SH, O'Kane CJ (1999), “Transgenic inhibitors identify two roles for protein kinase A in Drosophila development.” Genetics 152(1):281-90 Details O'Kane CJ, Asztalos Z (1999), “Sexual behaviour: Courting dissatisfaction.” Curr Biol 9(8):R289-92 Details 1998Chan HY, Zhang Y, Hoheisel JD, O'Kane CJ (1998), “Identification and characterization of the gene for Drosophila L3 ribosomal protein.” Gene 212(1):119-25 Details Edwin Chan HY, Harris SJ, O'Kane CJ (1998), “Identification and characterization of kraken, a gene encoding a putative hydrolytic enzyme in Drosophila melanogaster.” Gene 222(2):195-201 Details 1997Brunner A, O'Kane CJ (1997), “The fascination of the Drosophila NMJ.” Trends Genet 13(3):85-7 Details Chan HY, Zhang Y, O'Kane CJ (1997), “Identification and characterization of the gene for Drosophila S20 ribosomal protein.” Gene 200(1-2):85-9 Details Ferveur JF, Savarit F, O'Kane CJ, Sureau G, Greenspan RJ, Jallon JM (1997), “Genetic feminization of pheromones and its behavioral consequences in Drosophila males.” Science 276(5318):1555-8 Details 1996Connolly JB, Roberts IJ, Armstrong JD, Kaiser K, Forte M, Tully T, O'Kane CJ (1996), “Associative learning disrupted by impaired Gs signaling in Drosophila mushroom bodies.” Science 274(5295):2104-7 Details Phelan P, Nakagawa M, Wilkin MB, Moffat KG, O'Kane CJ, Davies JA, Bacon JP (1996), “Mutations in shaking-B prevent electrical synapse formation in the Drosophila giant fiber system.” J Neurosci 16(3):1101-13 Details Wolfgang WJ, Roberts IJ, Quan F, O'Kane C, Forte M (1996), “Activation of protein kinase A-independent pathways by Gs alpha in Drosophila.” Proc Natl Acad Sci U S A 93(25):14542-7 Details 1995Broadie K, Prokop A, Bellen HJ, O'Kane CJ, Schulze KL, Sweeney ST (1995), “Syntaxin and synaptobrevin function downstream of vesicle docking in Drosophila.” Neuron 15(3):663-73 Details Sweeney ST, Broadie K, Keane J, Niemann H, O'Kane CJ (1995), “Targeted expression of tetanus toxin light chain in Drosophila specifically eliminates synaptic transmission and causes behavioral defects.” Neuron 14(2):341-51 Details 1992Moffat KG, Gould JH, Smith HK, O'Kane CJ (1992), “Inducible cell ablation in Drosophila by cold-sensitive ricin A chain.” Development 114(3):681-7 Details 1990Bellen HJ, Wilson C, Gibson G, Grossniklaus U, Pearson RK, O'Kane C, Gehring WJ (1990), “P-element-mediated enhancer detection allows rapid identification of developmentally regulated genes and cell specific markers in Drosophila.” J Physiol (Paris) 84(1):33-41 Details 1989Bellen HJ, O'Kane CJ, Wilson C, Grossniklaus U, Pearson RK, Gehring WJ (1989), “P-element-mediated enhancer detection: a versatile method to study development in Drosophila.” Genes Dev 3(9):1288-300 Details Ghysen A, O'Kane C (1989), “Neural enhancer-like elements as specific cell markers in Drosophila.” Development 105(1):35-52 Details Wilson C, Pearson RK, Bellen HJ, O'Kane CJ, Grossniklaus U, Gehring WJ (1989), “P-element-mediated enhancer detection: an efficient method for isolating and characterizing developmentally regulated genes in Drosophila.” Genes Dev 3(9):1301-13 Details 1987O'Kane CJ, Gehring WJ (1987), “Detection in situ of genomic regulatory elements in Drosophila.” Proc Natl Acad Sci U S A 84(24):9123-7 Details 1986McConnell DJ, Cantwell BA, Devine KM, Forage AJ, Laoide BM, O'Kane C, Ollington JF, Sharp PM (1986), “Genetic engineering of extracellular enzyme systems of Bacilli.” Ann N Y Acad Sci 469:1-17 Details O'Kane C, Stephens MA, McConnell D (1986), “Integrable alpha-amylase plasmid for generating random transcriptional fusions in Bacillus subtilis.” J Bacteriol 168(2):973-81 Details |