Drosophila Neural Cell Biology
Drosophila, neuronal cell biology, neuromuscular junction, neurodegeneration, membrane traffic
We are interested in signaling processes that regulate neuronal function - both their basic biology, and their relevance to neurodegenerative disease. Of particular interest are the membrane traffic events relevant to these processes, using Drosophila as a model.
Axonal ER and hereditary spastic paraplegia
Axonal ER forms a continuous tubular network reaching from the rest of the ER in the cell body, all the way to presynaptic terminals. Its formation and function are poorly understood, but its organisation is 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, but their roles in formation and function of axonal ER are not known.
Using Drosophila, we have established roles for a number of HSP proteins in formation of axonal ER, by finding ER abnormalities in mutant axons. We aim to better understand the mechanism of its formation, as well as the physiological consequences of disrupting its presence or continuity.
Diseases of aggregate-prone proteins
Many neurodegenerative diseases are caused by aggregate-prone proteins like those containing polyglutamine. However, we do not fully understand the cellular responses to such proteins - a basic biological problem that is also relevant to effective therapies, which are currently lacking. A genome-wide screen here is identifying additional proteins that contribute to polyglutamine toxicity, and is starting to identify new players in relevant cellular processes such as autophagy and apoptosis.
Genetics and bioinformatics of brain circuitry
I am a member of the Virtual Fly Brain consortium, a hub for integration of brain anatomical, expression, phenotypic and genetic data in Drosophila. As the volume of such data increases, there is a need for easy access to it, similar to the ready access to genome data that has developed over recent decades.
4 key publications
- O'Sullivan NC, Jahn TR, Reid E, O'Kane CJ (2012) Reticulon-like-1, the Drosophila ortholog of the Hereditary Spastic Paraplegia gene reticulon 2, is required for organization of endoplasmic reticulum and of distal motor axons. Hum Mol Gen 21:3356-65 >> Link to paper
- 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 >> Link to paper
- 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: 177-85 >> Link to paper
- Koh 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: 309-22 (* Joint senior authors) >> Link to paper
Page updated 26 Aug 2014