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.
Membrane traffic and hereditary spastic paraplegia
We want to understand the cellular roles of proteins mutated in a class of motor neuron disease, hereditary spastic paraplegia (HSP). HSPs affect longer corticospinal motor tract axons, suggesting axon transport defects. However, most HSP genes encode intracellular membrane proteins, with no overt roles in axon transport. Recently we characterised one HSP protein as a regulator of BMP receptor traffic and signaling. We now want to understand how it works, and whether any of the other affected proteins have similar roles.
Synaptic membrane traffic
Our earlier work to dissect the mechanisms of synaptic vesicle release and endocytosis has led to results including tetanus toxin transgenic flies, a widely used tool for behavioural studies, and the finding that amphiphysin is important for T-tubule formation in muscles. Current work is focused on how membrane deformation induced by proteins like amphiphysin and endophilin is coupled to other events in the synapse.
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