Abstract: The axon acts as a conduit for organized transport of materials between the cell body and the synapse, a process that is essential for the function and survival of neurons. Defective axonal transport, such as accumulation of axonal cargoes, has been linked with a range of neurodegenerative diseases by extensive genetic and biochemical studies. However, it is still unclear whether and how defective axonal transport might play a role in the progression of neuronal degeneration. Genetic and biochemical approaches lack precise control over when and where the cargo accumulations will happen along the axon, which makes it difficult to pinpoint the role of """"""""""""""""transport defect"""""""""""""""" in the process of neuronal degeneration. In this proposal, we propose to engineer magnetic and optical forces that specifically stall a population of axonal cargoes that contain magnetic or optical nanoparticle probes at the trapping area. Physically stalling the cargoes would be one of the most direct means to perturb a cargo transport process, which, however, are technically challenging in live cells. We will overcome those challenges using advanced nanofabrication, imaging techniques and novel nanoparticle probes. Inside the narrow axon, stalled cargoes will act as roadblocks to slow down the trafficking of other probe-free cargoes that are not affected by external forces. Such force-induced traffic jams afford new approaches to investigate whether blocking the axonal transport is sufficient to induce neuronal degeneration and how cellular processes response to axonal traffic blockage. Public Health Relevance: Age-related neurodegenerative diseases, such as Alzheimer's disease, impact the lives of millions and pose a growing public health challenge. This study aims to investigate how defective axonal transport might cause or contribute to the progression of those neurodegenerative diseases. The findings of this research will advance our understanding of age-related neuronal death and assist therapeutic interventions for the treatment of these disorders.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
NIH Director’s New Innovator Awards (DP2)
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Special Emphasis Panel (ZGM1-NDIA-C (01))
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Ludwig, Kip A
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Stanford University
Schools of Arts and Sciences
United States
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Che, Daphne L; Chowdary, Praveen D; Cui, Bianxiao (2016) A close look at axonal transport: Cargos slow down when crossing stationary organelles. Neurosci Lett 610:110-6
Zhang, Kai; Cui, Bianxiao (2015) Optogenetic control of intracellular signaling pathways. Trends Biotechnol 33:92-100
Chowdary, Praveen D; Che, Daphne L; Kaplan, Luke et al. (2015) Nanoparticle-assisted optical tethering of endosomes reveals the cooperative function of dyneins in retrograde axonal transport. Sci Rep 5:18059
Duan, Liting; Che, Daphne; Zhang, Kai et al. (2015) Optogenetic control of molecular motors and organelle distributions in cells. Chem Biol 22:671-82
Ong, Qunxiang; Guo, Shunling; Zhang, Kai et al. (2015) U0126 protects cells against oxidative stress independent of its function as a MEK inhibitor. ACS Chem Neurosci 6:130-7
Che, Daphne L; Duan, Liting; Zhang, Kai et al. (2015) The Dual Characteristics of Light-Induced Cryptochrome 2, Homo-oligomerization and Heterodimerization, for Optogenetic Manipulation in Mammalian Cells. ACS Synth Biol 4:1124-35
Hanson, Lindsey; Zhao, Wenting; Lou, Hsin-Ya et al. (2015) Vertical nanopillars for in situ probing of nuclear mechanics in adherent cells. Nat Nanotechnol 10:554-62
Zhang, Kai; Cui, Bianxiao (2014) Lighting up FGFR signaling. Chem Biol 21:806-8
Lin, Ziliang Carter; Xie, Chong; Osakada, Yasuko et al. (2014) Iridium oxide nanotube electrodes for sensitive and prolonged intracellular measurement of action potentials. Nat Commun 5:3206
Zhang, Kai; Fishel Ben Kenan, Rotem; Osakada, Yasuko et al. (2013) Defective axonal transport of Rab7 GTPase results in dysregulated trophic signaling. J Neurosci 33:7451-62