This Core will provide support to Projects 1, 2 and 3 by providing molecular tools to manipulate gene expression in the proposed studies, and by providing support for the cell-specific isolation of mRNA from target cell types, and for RT-PCR analysis of that RNA to assess changes in gene expression.
Aim 1 will be to design, develop, and validate recombinant adeno-associated viral expression vectors (rAAVs) for distribution to Projects 1-3. These vectors will be used to express proteins under the control of tissue-specific promoters, either in vivo using stereotaxic injection, or in cultured iPSc-derived dopaminergic neurons.
Aim 2 will be to design, develop and validate rAAVs to be used for delivery of shRNA gene knock down constructs for use in each of the Projects.
Aim 3 will be to provide services involving cell-specific isolation of RNA from targeted cells using RiboTag-based isolation of mRNA, and to identify and quantify genes undergoing changes in expression/translation, by RT-PCR analysis of that mRNA. Core B team members are highly skilled in the development and use of these tools. Finally, this Core will support the Projects by developing novel molecular tools, should the need arise.
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| Guzman, Jaime N; Ilijic, Ema; Yang, Ben et al. (2018) Systemic isradipine treatment diminishes calcium-dependent mitochondrial oxidant stress. J Clin Invest 128:2266-2280 |
| Burbulla, Lena F; Song, Pingping; Mazzulli, Joseph R et al. (2017) Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinson's disease. Science 357:1255-1261 |
| Dodla, Ramana; Wilson, Charles J (2017) Effect of Phase Response Curve Shape and Synaptic Driving Force on Synchronization of Coupled Neuronal Oscillators. Neural Comput 29:1769-1814 |
| Abrahao, Karina P; Chancey, Jessica H; Chan, C Savio et al. (2017) Ethanol-Sensitive Pacemaker Neurons in the Mouse External Globus Pallidus. Neuropsychopharmacology 42:1070-1081 |
| Surmeier, D James; Obeso, José A; Halliday, Glenda M (2017) Parkinson's Disease Is Not Simply a Prion Disorder. J Neurosci 37:9799-9807 |
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| Surmeier, D James; Obeso, José A; Halliday, Glenda M (2017) Selective neuronal vulnerability in Parkinson disease. Nat Rev Neurosci 18:101-113 |
| Chu, Hong-Yuan; McIver, Eileen L; Kovaleski, Ryan F et al. (2017) Loss of Hyperdirect Pathway Cortico-Subthalamic Inputs Following Degeneration of Midbrain Dopamine Neurons. Neuron 95:1306-1318.e5 |
| Shi, Han; Deng, Han-Xiang; Gius, David et al. (2017) Sirt3 protects dopaminergic neurons from mitochondrial oxidative stress. Hum Mol Genet 26:1915-1926 |
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