Engineering external forces for manipulating cargo transport in live neurons

设计外力来操纵活神经元中的货物运输

• 批准号: 8358351
• 负责人: Bianxiao Cui
• 金额: $ 235.5万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-30 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8358351
• 关键词: Affect; Alzheimer' s Disease; Area; Assisted Suicide; Axon; Axonal Transport; Biochemical; Cell physiology; Cells; Defect; Disease; Engineering; Genetic; Imaging Techniques; Life; Link; Magnetism; Nerve Degeneration; Neurodegenerative Disorders; Neurons; Optics; Play; Population; Process; Public Health; Research; Role; Synapses; Therapeutic Intervention; Transport Process; abstracting; age related; nanofabrication; nanoparticle; neuronal cell body; novel; novel strategies; public health relevance; response; trafficking

DESCRIPTION (Provided by the applicant) 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.

描述（由申请人提供）

项目成果

Imaging electric field dynamics with graphene optoelectronics.

• DOI: 10.1038/ncomms13704
• 发表时间: 2016-12-16
• 期刊: Nature communications
• 影响因子: 16.6

Construction of Light-Activated Neurotrophin Receptors Using the Improved Light-Induced Dimerizer (iLID).

• DOI: 10.1016/j.jmb.2020.04.018
• 发表时间: 2020-06-12
• 期刊: JOURNAL OF MOLECULAR BIOLOGY
• 影响因子: 5.6
• 作者: Hope, Jen M.;Liu, Aofei;Calvin, Ghawayne J.;Cui, Bianxiao
• 通讯作者: Cui, Bianxiao

Iridium oxide nanotube electrodes for sensitive and prolonged intracellular measurement of action potentials.

• DOI: 10.1038/ncomms4206
• 发表时间: 2014
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Lin, Ziliang Carter;Xie, Chong;Osakada, Yasuko;Cui, Yi;Cui, Bianxiao
• 通讯作者: Cui, Bianxiao

Optogenetic control of molecular motors and organelle distributions in cells.

• DOI: 10.1016/j.chembiol.2015.04.014
• 发表时间: 2015-05-21
• 期刊: Chemistry & biology
• 作者: Duan L;Che D;Zhang K;Ong Q;Guo S;Cui B
• 通讯作者: Cui B

A close look at axonal transport: Cargos slow down when crossing stationary organelles.

• DOI: 10.1016/j.neulet.2015.10.066
• 发表时间: 2016-01-01
• 期刊: Neuroscience letters
• 影响因子: 2.5
• 作者: Che DL;Chowdary PD;Cui B
• 通讯作者: Cui B