Proteomic Core D

蛋白质组核心D

• 批准号: 10496284
• 负责人: Ying Zhu
• 金额: $ 12.71万
• 依托单位: UNIVERSITY OF NEVADA RENO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10496284
• 关键词: Action Potentials; Address; Affect; Aging; Auditory; Auditory area; Biochemical; Biochemistry; Biological Markers; Biological Process; Cell physiology; Cells; Cellular Structures; Clinical; Cochlear nucleus; Code; Complex; Cytometry; Demyelinations; Detection; Disease; FDA approved; Functional disorder; Genetic; Immunohistochemistry; Individual; Inhibitory Synapse; Joints; Liquid substance; Mass Spectrum Analysis; Measurement; Measures; Mediating; Modeling; Molecular; Nature; Nerve Degeneration; Neurons; Outcome; Persons; Pharmaceutical Preparations; Phase; Pitch Perception; Post-Translational Protein Processing; Predisposition; Presbycusis; Process; Program Research Project Grants; Property; Proteins; Proteome; Proteomics; Public Health; RNA; Regulation; Resolution; Resources; Sensorineural Hearing Loss; Speech Intelligibility; Speed; Stimulus; Synapses; Synaptic plasticity; Techniques; Testing; Therapeutic; age related; aged; aging auditory system; aging population; auditory pathway; blind; design; excitotoxicity; functional plasticity; improved; innovation; mouse model; neural; neural network; neuron loss; neurosensory; neurotransmission; protein biomarkers; response; single cell proteins; single-cell RNA sequencing; sound; spiral ganglion; tool

Abstract Complex biological processes like auditory neural aging are composed of dynamic changes in individual neurons' biochemistry, with various aging process susceptibilities. Direct measures of a single auditory neuron (spiral ganglion neuron (SGN) and cochlear nuclei (CN) neuron subtypes) and their age-related alterations are needed to characterize cellular transitions, regulatory mechanisms, and the microenvironment's contribution to age- related hearing loss (ARHL). A critical unmet need is determining the biochemical makeup of healthy and aged SGNs with single-cell resolution and a depth of coverage extending to thousands of biomolecules. Proteins mediate the bulk of cellular function, and the correlation between RNA and protein abundance is often lacking, and the proteome largely determines cellular structure and function. We hypothesize that the aging SGN undergoes a profound proteomic dynamic that is neuron subtype-specific. The aims of Core D are: 1. To refine liquid chromatograph-mass spectrometry (LC-MS)-based proteomics platform for sensitive and high-throughput SGN proteomics. 2. To apply the improved platform to study aging-related proteome regulations for SGN and CN subtypes and at single-cell resolution. The proposed effort will result in a processing and analysis platform capable of direct and unbiased profiling of SGNs and CN neurons with a depth of coverage of >3000 proteins/cell, thus providing a capability for direct protein measurement analogous to single-cell RNA-seq. Core D serves as a resource to identify ARHL biomarkers for Projects 1-3 to test and perform functional analyses. Outcomes will produce unbiased and in- depth single-cell protein profiles of SGNs and CN to provide a complete picture and identify protein biomarkers associated with ARHL.

抽象的 听觉神经老化等复杂的生物过程是由单个神经元的动态变化组成的。 生物化学，具有各种衰老过程的敏感性。单个听觉神经元的直接测量（螺旋 需要神经节神经元（SGN）和耳蜗核（CN）神经元亚型）及其与年龄相关的改变 表征细胞转变、调节机制和微环境对年龄的贡献 相关听力损失（ARHL）。一个未满足的关键需求是确定健康和老年人的生化组成 SGN 具有单细胞分辨率和覆盖数千个生物分子的深度。蛋白质 介导大部分细胞功能，而 RNA 和蛋白质丰度之间往往缺乏相关性， 蛋白质组在很大程度上决定了细胞的结构和功能。我们假设老化的SGN 经历了神经元亚型特异性的深刻的蛋白质组动态。 核心 D 的目标是： 1. 完善基于液相色谱-质谱（LC-MS）的蛋白质组学平台，用于敏感和 高通量 SGN 蛋白质组学。 2. 应用改进的平台研究SGN和CN亚型与衰老相关的蛋白质组调控 在单细胞分辨率下。 拟议的工作将产生一个处理和分析平台，能够直接和公正地分析 SGN 和 CN 神经元的覆盖深度超过 3000 个蛋白质/细胞，从而提供了直接 类似于单细胞 RNA 测序的蛋白质测量。核心 D 作为识别 ARHL 的资源 项目 1-3 的生物标志物用于测试和执行功能分析。结果将产生公正和in- SGN 和 CN 的深度单细胞蛋白质谱，提供完整的图片并识别蛋白质生物标志物 与 ARHL 相关。