Chris Elliott's Home page

Chris Elliott, Lecturer in Biology at the University of York, UK

Role of Parkinson's disease genes in flies

Research outline

Model organisms, like flies, provide a rapid experimental system to study the causes of Parkinson's disease. I collaborate with Sean Sweeney, Alex Wade Gareth Evans, Sangeeta Chawla, Gonzalo Blanco and Will Brackenbury to form the York Neuroscience Group, where we focus on neurotransmission in model systems.

My key question is how cellular defects (e.g. faulty mitochondria) lead to physiological and behavioural abnormalities - In Parkinson's Disease (PD), why do some neurons die, while others function normally?

LRRK2

We find that flies expressing the G2019S mutation (but not other mutations in LRRK2) have accelerated loss of vision, and this is most pronounced when the G2019S transgene is expressed in just the dopaminergic neurons. Our data

suggests a hypothesis, that differences between older reports on visual defects in PD patients may arise from genetic differences between the patients.
shows that expressing the G2019S mutation in the dopaminergic neuron leads to loss of function in different kinds of neuron - e.g. the photoreceptors, which have nothing to do with dopamine.
shows that increasing the activity of the visual system accelerates the decline in the G2019S mutation

Details here. This work is being pursued in collaboration with Alex Wade and Naz Afsari on a Wellcome Trust grant, and by Rebecca Furmston and Stavroula Petridi on White Rose and Parkinson's UK studentships.

parkin

We find that parkin mutants crawl more slowly, with a bradykinesia-like phenotype, in which neural function is impaired, and muscle function remains intact. In the CNS, the metabolic function is impaired, and neurotransmission disrupted. The way in which this is related to oxidative stress is being explored by a BBSRC funded research student, Amanda Vincent.

Other work with flies...

how diet affects muscle performance, and this is being explored by Jenny Hsu
how the nervous system uses neurotransmitters even if they don't seem essential for survival. For example, a null mutant which synthesizes no octopamine survives without this amine. We have shown that it jumps less well and that the ovaries and oviducts are less effective at moving eggs along the reproductive tract. So that flies seem to need this neurotransmitter for full fitness. (Work done in collaboration with Julia Hill). While octopamine is needed for movement in the female reproductive tract, serotonin seems to modulate the male reproductive tract.

Snails

My earlier work at York was with the pond snail Lymnaea stagnalis. This is what the snails look like. In particular, I'm interested in how their nervous system controls feeding behaviour, because this is a really robust model system. A major part of my time was taken up with using laser ablation and pharmacological tools to analyze the neural circuits. My key finding was that octopamine is very important in the feeding system, as it modulates the behaviour at multiple levels, making it more efficient and longer lasting.

Computer Software

I (intermittently) write computer software to aid in the modeling of nervous systems: read (&download) all about the Hodgkin-Huxley simulation and Connor (with IA) models.

Recent publications include

72. Middleton, C.A., Nongthomba, U., Parry, K., Sweeney, S.T., Sparrow, J.C. Elliott, C.J.H. (2006) Neuromuscular organization and aminergic modulation of contractions in the Drosophila ovary BMC Biology 4:17 Full text (free access)
73. Large, C.J., Smith, T., Foulds, G., Currey, J.D. and Elliott, C.J.H. (2006) Leaf mechanical properties modulate feeding movements and ingestive success of the pond snail, Lymnaea stagnalis. Invert. Neurosci. 6: 133-140 Abstract
74. Ormshaw, J. C., C. J. H. Elliott (2006) Octopamine boosts snail locomotion: behavioural and cellular analysis. Invert. Neurosci 6: 215-220. Abstract
75. Vehovszky, A., Szabo, H., Hiripi, L., Elliott, C.J.H. and Hernadi, L. (2007) Behavioural and neural deficits induced by rotenone in the pond snail Lymnaea stagnalis. A possible model for Parkinson’s disease in an invertebrate. Eur J. Neurosci 25:2123–2130 Abstract
76. Elliott, C.J.H. Brunger, H., Stark, M. and Sparrow, J.C. (2007) Direct measurement of the performance of the Drosophila jump muscle in whole flies. Fly 1:68 - 74 Abstract
78. Harvey, J., Brunger, H., Middleton, C.A., Hill, J.A., Sevdali, M.,. Sweeney, S.T., Sparrow, J.C. and Elliott, C. J. H. (2008) Neuromuscular control of a single twitch muscle in wild type and mutant Drosophila, measured with an ergometer. Invertebrate neuroscience 8:63-70 Abstract Author manuscript
79. Norville, K., Sweeney, S.T. and Elliott, C.J.H (2010) Post mating change in physiology of male Drosophila mediated by 5-HT. J. Neurogentics 24: 27–32 Abstract Author manuscript
80. Elliott, C. J. H. and Sparrow, J.C. (2012) In vivo measurement of muscle output in intact Drosophila. Methods 56:78-86 Abstract Author manuscript Supplementary movie
81. Vincent, A., Briggs, L., Chatwin, G.F.J., Emery, E., Tomlins, R., Oswald, M., Middleton, C.A., Evans, G.J.O., Sweeney, S.T., Sparrow, J.C. and Elliott, C.J.H. (2012) parkin induced defects in neurophysiology and locomotion are generated by metabolic dysfunction and not oxidative stress. Hum. Mol. Gen. 21: 1760-1769, Abstract & Free Full text
82. Katzemich A R, Kreisk\F6ther N, Alexandrovich A, Elliott, C J H, Sch\F6ck F, Leonard K R, Sparrow J C, and Bullard, B. (2012) The function of the M-line protein, obscurin, in controlling the symmetry of the sarcomere in Drosophila flight muscle. J cell Sci. 125, 3367-3379 Abstract
83. Diaper D C, Yoshitsugu A, Sutcliffe B, Humphrey, D M, Elliott, C J H, Stepto A, Ludlow Z N, Vanden Broeck L, Callaerts P, Dermaut B, Al-Chalabi A, Shaw C E, Robinson IM and Frank Hirth (2013) Loss and gain of Drosophila TDP-43 impair synaptic efficacy and motor control leading to age-related neurodegeneration by loss. Hum. Mol. Genetics 22: 1539-1557 Abstract and free Full text
84. Hindle, S., Afsari, F, Stark, M, Middleton, C.A., Evans, G J O, Sweeney, S T, and Elliott, C J H (2013) Dopaminergic expression of the Parkinsonian gene LRRK2-G2019S leads to non-autonomous visual neurodegeneration, accelerated by increased neural demands for energy. Hum. Mol. Genetics 22: 2129-2140 Abstract and free Full text
85. Hindle, S. & Elliot, C.J.H. (2013) Spread of neuronal degeneration in a dopaminergic, Lrrk2-G2019S model of Parkinson's disease. Autophagy. 9: 936-938. Abstract and Free Full text
86. Afsari, F., Christensen, K.V., Smith, G.P., Hentzer, M., Nippe, O.M., Elliott, C.J.H. and Wade, A.R. (2014) Abnormal visual gain control in a Parkinson's Disease model Hum. Mol. Genetics 23: 4465-4478 Abstract and free full text
87. Fogg, P.C.M., O'Neill, J.S., Dobrzycki, T., Calvert, S., Lord, E.C., McIntosh, R.L.L., Elliott, C.J.H., Sweeney, S.T., Hastings, M.H. and Chawla, S. (2014) Class IIa histone deacetylases are conserved regulators of circadian function. J. Biol. Chem. 289: 34341-34348 Abstract and Free full text
88. Wade, A.R. and Elliott, C.J.H. (2014) Could the detection of visual disturbances associated with Parkinsons disease genes in flies lead to new treatments for the disease? Neurodegenerative Disease Management 4:291-293 Abstract and Free Full text
89. West, R. J.H. Furmston, R., Williams, C.A.C & Elliott, C.J.H. (2015) Neurophysiology of Drosophila models of Parkinson's Disease Parkinson's disease 2015:381281 Abstract and free full text
90. Orfanos, Z., Leonard, K., Elliott, C.J.H., Katzemich, A., Bullard, B., & Sparrow, J.C (2015) Sallimus and the dynamics of sarcomere assembly in Drosophila flight muscles. J mol biol 427: 215-218 Abstract and free full text
91. Smith, S.L., Lones, M., Bedder, M. Alty, J.A., Cosgrove, J., Maguire, R.J. & Pownall, M.E., Ivanoiu, D., Lyle, C., Cording, A. & Elliott, C.J.H., (2015) Computational models for understanding the diagnosis and treatment of Parkinsons disease. IET Systems Biology Abstract Full Text (Pubmed)
92. Mortiboys, H., Furmston, R., Bronstad, G., Aasly, J., Elliott, C.J.H., & Bandmann, O. (2015) UDCA exerts beneficial effect on mitochondrial dysfunction in LRRK2 G2019S carriers and in vivo. Neurology Abstract Free full text
93.West, R. J.H., Elliott, C.J.H. & Wade, A.R. (2015) Classification of Parkinson’s Disease Genotypes in Drosophila Using Spatiotemporal Profiling of Vision. Nature Sci Rep 5:16933 Abstract and free full text
94. Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, ... Elliott, C.J.H. ... Zorzano A, & Zughaier SM. (2016) Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy. 12:1-222. Abstract & Free Full text
95.Hindle, S. Hebbar, S. Schwudke, D. Elliott, C.J.H. & Sweeney, S.T., (2017) A Saposin deficiency model in Drosophila: lysosomal storage, progressive neurodegeneration, sensory physiological decline and defective calcium homeostasis. Neurobiol. Dis. 98:77-87 Abstract & Free Full text
96.Augustin, H., Adcott, J., Elliott, C.J.H. & Partridge, L. (2017) Complex Roles of Myoglianin in Regulating Adult Performance and Lifespan. Fly: Online early, Abstract & Free Full text

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Chris Elliott

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