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Department
  • Genetics
  • Research Focus

    Keywords

  • Axon Endoplasmic Reticulum
  • Drosophila
  • Axon Degeneration
  • Hereditary Spastic Paraplegia
  • Clinical Conditions

  • Hereditary spastic paraplegia
  • Equipment & Techniques

  • Calcium imaging
  • Confocal microscopy
  • Fluorescence microscopy
  • Science Culture

  • Science & Social Media
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    Professor Cahir O'Kane

    University Position
    Professor
    Professor Cahir O'Kane is pleased to consider applications from prospective PhD students.

    Interests

    We 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 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. We are particularly interested in the biophysical consequences of the tiny lumen diameter of axonal ER, and in testing predictions from our Drosophila work about the impact of ER continuity, density and diameter on susceptibility to axon degeneration.

    Axonal ER extends all the way to motor neurone terminals

    Rtnl1::YFP (green) stretches continuously through axons all the way to the tips of motor neurone presynaptic termini in Drosophila larvae. Image credit: Niamh O'Sullivan.

    Collaborators

    Cambridge
  • Edward Avezov
  • External
  • Mark Terasaki
  • Key Publications

    Drosophila SPG12 ortholog, reticulon-like 1, governs presynaptic ER organization and Ca2+ dynamics.

    DOI: http://doi.org/10.1083/jcb.202112101
    Journal: J Cell Biol
    E-pub date: 5 Jun 2023
    Authors: JJ Pérez-Moreno, RC Smith, MK Oliva, F Gallo, S Ojha, KH Müller, CJ O'Kane

    Axonal Endoplasmic Reticulum Dynamics and Its Roles in Neurodegeneration.

    DOI: http://doi.org/10.3389/fnins.2020.00048
    Journal: Front Neurosci
    E-pub date: 1 Aug 2020
    Authors: Z Öztürk, CJ O'Kane, JJ Pérez-Moreno

    Modeling of axonal endoplasmic reticulum network by spastic paraplegia proteins.

    DOI: http://doi.org/10.7554/eLife.23882
    Journal: Elife
    E-pub date: 25 Jul 2017
    Authors: B Yalçın, L Zhao, M Stofanko, NC O'Sullivan, ZH Kang, A Roost, MR Thomas, S Zaessinger, O Blard, AL Patto, A Sohail, V Baena, M Terasaki, CJ O'Kane

    Publications

    Octopaminergic neurons have multiple targets in Drosophila larval mushroom body calyx and can modulate behavioral odor discrimination.

    DOI: http://doi.org/10.1101/lm.052159.120
    Journal: Learn Mem
    E-pub date: 1 Feb 2021
    Authors: JYH Wong, BA Wan, T Bland, M Montagnese, AD McLachlan, CJ O'Kane, SW Zhang, LM Masuda-Nakagawa

    Endoplasmic Reticulum Lumenal Indicators in Drosophila Reveal Effects of HSP-Related Mutations on Endoplasmic Reticulum Calcium Dynamics.

    DOI: http://doi.org/10.3389/fnins.2020.00816
    Journal: Front Neurosci
    E-pub date: 1 Aug 2020
    Authors: MK Oliva, JJ Pérez-Moreno, J O'Shaughnessy, TJ Wardill, CJ O'Kane

    GAL4 Drivers Specific for Type Ib and Type Is Motor Neurons in Drosophila.

    DOI: http://doi.org/10.1534/g3.118.200809
    Journal: G3 (Bethesda)
    E-pub date: 7 Feb 2019
    Authors: JJ Pérez-Moreno, CJ O'Kane

    Complex inhibitory effects of nitric oxide on autophagy.

    DOI: http://doi.org/10.1016/j.molcel.2011.04.029
    Journal: Mol Cell
    E-pub date: 8 Jul 2011
    Authors: S Sarkar, VI Korolchuk, M Renna, S Imarisio, A Fleming, A Williams, M Garcia-Arencibia, C Rose, S Luo, BR Underwood, G Kroemer, CJ O'Kane, DC Rubinsztein

    Antioxidants can inhibit basal autophagy and enhance neurodegeneration in models of polyglutamine disease.

    DOI: http://doi.org/10.1093/hmg/ddq253
    Journal: Hum Mol Genet
    E-pub date: 1 Sep 2010
    Authors: BR Underwood, S Imarisio, A Fleming, C Rose, G Krishna, P Heard, M Quick, VI Korolchuk, M Renna, S Sarkar, M García-Arencibia, CJ O'Kane, MP Murphy, DC Rubinsztein

    Rapamycin alleviates toxicity of different aggregate-prone proteins.

    DOI: http://doi.org/10.1093/hmg/ddi458
    Journal: Hum Mol Genet
    E-pub date: 1 Feb 2006
    Authors: Z Berger, B Ravikumar, FM Menzies, LG Oroz, BR Underwood, MN Pangalos, I Schmitt, U Wullner, BO Evert, CJ O'Kane, DC Rubinsztein