Approaches used extensively in the Burton laboratory include: generation and characterization of novel transgenic and gene knockout zebrafish models to study the neurobiology of disease in vivo; development and deployment of automated high throughput neurobehavioral and imaging assays for unbiased phenotype-based chemical biology approaches; use of intravital imaging, novel chemoptogenetic systems and electrophysiological recordings to understand pathophysiological mechanisms in CNS neurons in vivo. Current areas of focus include:
- Exploiting the optical transparency of zebrafish in order to allow live imaging in vivo of changes in neuronal mitochondrial function during the pathogenesis of synuclein and tau models.
- Investigating the role of mitochondrial-telomeric ROS flux using novel transgenic zebrafish expressing chemoptogenetic sensitizers at different subcellular locations
- Utilizing medium-throughput reverse genetics in zebrafish to determine the role of genes near risk-associated SNPs identified by GWAS studies in Parkinson’s disease and progressive supranuclear palsy
- Unbiased phenotype-driven chemical modifier screens in zebrafish synuclein and tau models to discover novel molecular modulators and their targets
- Using electrophysiological methods to understand how neuronal signaling is altered early in the pathophysiology of synuclein and tau models
Bai, Q., Garver, J. A., Hukriede, N. A., Burton, E. A. (2007). Generation of a transgenic zebrafish model of Tauopathy using a novel promoter element derived from the zebrafish eno2 gene. Nucleic Acids Res. 35 (19), 6501-16
Farrell, T. C., Cario, C. L., Milanese, C., Vogt, A., Jeong, J.-H., Burton, E. A. (2011) Evaluation of spontaneous propulsive movement as a screening tool to detect rescue of Parkinsonism phenotypes in zebrafish models. Neurobiology of Disease. 44(1), 9-18.
[Featured on the cover of the October 2011 issue of NBD]
Milanese, C., Sager, J. J., Bai, Q., Farrell, T. C., Cannon, J. R., Greenamyre, J. T., Burton, E. A. (2012) Hypokinesia and reduced dopamine levels in zebrafish lacking β- and γ1-synucleins. J Biol Chem. 287(5):2971-83
[Featured on the cover of the January 27, 2012 issue of JBC]
Zhou, Y., Cattley, R. T., Cario, C. L., Bai, Q., Burton, E. A. (2014) Quantification of larval zebrafish motor function in multi-well plates using open-source MATLAB applications. Nature Protocols. 9(7):1533-1548
[Featured on the cover of the July 2014 issue of Nature Protocols]
Zharikov, A., Cannon, J. R., Tapias, V., Bai, Q., Horowitz, M. P., Shah, V., El Ayadi, A., Hastings, T. G., Greenamyre, J. T., Burton, E. A. (2015) shRNA targeting α-synuclein prevents neurodegeneration in a Parkinson’s disease model. Journal of Clinical Investigation. 125(7):2721-2735
[Featured as a “Scientific Show Stopper” with accompanying commentary on JCI website]
Dukes, A. D., Bai, Q., Van Laar, V. S., Zhou, Y., Ilin, V., David, C. N., Agim, Z. S., Bonkowsky, J. L., Cannon, J. R., Watkins, S. C., St. Croix, C. M., Burton, E. A. and Berman, S. B. (2016) Live imaging of mitochondrial dynamics in CNS dopaminergic neurons in vivo demonstrates early reversal of mitochondrial transport following MPP+ exposure. Neurobiology of Disease 95:238-249
[Burton E. A. and Berman S. B. joint corresponding authors]
Scheetz, S. D., Shao, E., Zhou, Y., Cario, C. L., Bai, Q., and Burton, E. A. (2018). An open-source method to analyze optokinetic reflex responses in larval zebrafish. J Neurosci Methods 293: 329-337.