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Virus-like intercellular communication in the nervous system

神经系统中类似病毒的细胞间通讯

基本信息

批准号：
9790850
负责人：
Edward M Campbell
金额：
$ 106.84万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-01 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9790850
关键词：
Address Biological Assay Brain Capsid Cell Communication Cell Nucleus Cells Cognition Communication Cytoplasm Dendrites Endogenous Retroviruses Gene Transfer Genes Genetic Goals HIV HIV-1 Infection Information Storage Integral Membrane Protein Knowledge Lead Mediating Membrane Fusion Memory Messenger RNA Methodology Methods Modeling Molecular Monitor Nervous system structure Neuroglia Neurons Neurosciences Neurotransmitter Receptor Pathway interactions Process Property Proteins RNA RNA-Binding Proteins Research Personnel Research Project Grants Retroelements Retrotransposon Retroviridae Retrovirology Role Signal Transduction Structure Synapses Synaptic plasticity Testing Translating Translations Vesicle Viral Viral Genome Virus experience extracellular vesicles gag Gene Products genetic information innovation insight intercellular communication long term memory neuron development novel particle recruit spatiotemporal tool trafficking transmission process viral RNA

项目摘要

Abstract Recent studies by our group have revealed that the neuronal gene Arc, a master regulator of synaptic plasticity and information storage in the brain, acts as a repurposed retroviral Gag protein that forms capsids with the capacity to transmit genetic information between cells. These findings lead to a paradigm shift in the way we view both mechanisms of cognition and more generally how cells can signal to each other. This transformative R01 application will address these questions using a synergistic team of neuroscientists and virologists who will apply their expertise to Arc, intercellular gene transmission, and neuronal development. We will determine what genetic messages are transferred between neurons in Arc particles, how these particles enter “target” neurons to deliver their RNA cargo to cell cytoplasm, and how delivery of this cargo influences the neuronal and synaptic processes that underlie memory and cognition. The methodologies to address these questions, as well as the potential impact of the answers, make this application ideally suited to the transformative R01 mechanism.

摘要我们小组最近的研究表明，神经元基因Arc，一个主要的调节因子，突触可塑性和大脑中的信息存储，作为一种重新利用的逆转录病毒Gag蛋白形成具有在细胞之间传递遗传信息能力的衣壳。这些发现导致我们看待认知机制和更普遍的方式的范式转变细胞之间是如何相互传递信号的这一变革性的R01应用程序将解决这些问题利用神经科学家和病毒学家的协同团队提出问题，到Arc，细胞间基因传递和神经元发育。我们将决定遗传信息在Arc粒子中的神经元之间传递，这些粒子如何进入 “靶向”神经元将其RNA货物运送到细胞质，以及如何运送这种货物影响记忆和认知的神经元和突触过程。的解决这些问题的方法，以及答案的潜在影响，该应用程序非常适合R01的变革机制。