Millard, Sean - University of Queensland - School of Biomedical Sciences

研究领域

We are investigating the molecular mechanisms for wiring the brain using Drosophila melanogaster as a model system. Dscam2 mechanistic studies Dscam2 is a cell surface protein expressed on neurons and required for many different aspects of neurodevelopment. We have shown that it can mediate homophilic repulsion to form boundaries in the brain and homophilic adhesion to guide neurons to their correct synaptic target. Dscam2 also plays a role in synapse formation by instructing neurons where not to form synapses (a redundant role with its paralogue, Dscam1). Dscam2 produces two biochemically distinct protein isoforms and we have shown that cell-specific splicing of this gene is required for neurodevelopment. Several projects in the lab focus on how Dscam2 functions at the molecular level and how it can perform so many diverse functions in the brain. Dscam2 sleep studies In collaboration with the van Swinderen lab at QBI, we are investigating a role for Dscam2 in sleep. Using a Drosophila ARousal Tracking system (DART), we can measure sleep and many other sleep-related behaviours in the fly. The goal of this project is to better understand how a cell surface protein, like Dscam2 contributes to the development and/or the maintenance of sleep circuitry. Disease-related projects Two projects in the lab unrelated to Dscam2 are in the early stages of development. The first is a collaboration between my lab and Naomi Wray’s lab at QBI to investigate whether candidate ALS genes play a role at the neuromuscular junction (NMJ) of the fly. The second project involves using the fly model system to study epilepsy. This is a collaboration with Steve Petrou at the Florey Institute in Melbourne. The goal is to set-up an assay to study epilepsy in flies and then test various drug candidates in this system.

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Tadros, Wael, Xu, Shuwa, Akin, Orkun, Yi, Caroline H., Shin, Grace Ji-eun, Millard, S. Sean and Zipursky, S. Lawrence (2016) Dscam proteins direct dendritic targeting through adhesion. Neuron, 89 3: 480-493. doi:10.1016/j.neuron.2015.12.026 Bosch, Danny S., van Swinderen, Bruno and Millard, S. Sean (2015) Dscam2 affects visual perception in Drosophila melanogaster. Frontiers in Behavioral Neuroscience, 9 June: 1-13. doi:10.3389/fnbeh.2015.00149 Li, Joshua Shing Shun, Shin, Grace Ji-eun and Millard, Sean S. (2015) Neuronal cell-type-specific alternative splicing: A mechanism for specifying connections in the brain?. Neurogenesis, 2 1: e1122699.1-e1122699.5. doi:10.1080/23262133.2015.1122699 Lah, Grace Ji-eun, Li, Joshua Shing Shun and Millard, S. Sean (2014) Cell-specific alternative splicing of Drosophila Dscam2 is crucial for proper neuronal wiring. Neuron, 83 6: 1376-1388. doi:10.1016/j.neuron.2014.08.002 Li, Qingyun, Ha, Tal Soo, Okuwa, Sumie, Wang, Yiping, Wang, Qian, Millard, S. Sean, Smith, Dean P. and Volkan, Pelin Cayirlioglu (2013) Combinatorial rules of precursor specification underlying olfactory neuron diversity. Current Biology, 23 24: 2481-2490. doi:10.1016/j.cub.2013.10.053 Paulk, Angelique, Millard, S. Sean and van Swinderen, Bruno (2013) Vision in Drosophila: seeing the world through a model's eyes. Annual Review of Entomology, 58 313-332. doi:10.1146/annurev-ento-120811-153715 Millard, S. Sean, Lu, Zhiyuan, Zipursky, S. Lawrence and Meinertzhagen, Ian A. (2010) Drosophila Dscam proteins regulate postsynaptic specificity at multiple-contact synapses. Neuron, 67 5: 761-768. doi:10.1016/j.neuron.2010.08.030 Hattori, D., Millard, S. S., Wojtowicz, W. M. and Zipursky, S. L. (2008) Dscam-mediated cell recognition regulates neural circuit formation. Annual Review of Cell And Developmental Biology, 24 597-620. doi:10.1146/annurev.cellbio.24.110707.175250 Millard, S. Sean and Zipursky, S. Lawrence (2008) Dscam-mediated repulsion controls tiling and self-avoidance. Current Opinion In Neurobiology, 18 1: 84-89. doi:10.1016/j.conb.2008.05.005 Millard, S. S., Flanagan, J. J., Pappu, K. S., Wu, W. and Zipursky, S. L. (2007) Dscam2 mediates axonal tiling in the Drosophila visual system. Nature, 447 7145: 720-724. doi:10.1038/nature05855 Wojtowicza, Woj M., Flanagan, John J., Millard, S. Sean, Zipursky, S.Lawrence and Clemens, James C. (2004) Alternative splicing of Drosophila Dscam generates axon guidance receptors that exhibit isoform-specific homophilic binding. Cell, 118 5: 619-633. doi:10.1016/j.cell.2004.08.021