RNA regulatory networks in neuronal cell type diversity and function

神经元细胞类型多样性和功能中的 RNA 调控网络

基本信息

  • 批准号:
    10342485
  • 负责人:
  • 金额:
    $ 62.5万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-12-01 至 2026-11-30
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY RNA regulatory networks in neuronal cell type diversity and function The mammalian brain is probably the most complex organ in the body and its proper function requires coordination of many diverse types of excitatory and inhibitory neurons that form distinct functional circuitries. Characterization of neuronal cell types is fundamental to understand not only how the brain works, but also how specific cell types are selectively affected in multiple neuronal disorders and how this process can be reversed. A large number of neuronal cell types were recently defined based on their gene expression profiles in bulk and single cells, and these cell types are organized into a hierarchical cell taxonomy. Alternative splicing is a mechanism to generate multiple transcript and protein variants with distinct functions, thus providing a major driving force of the molecular diversity in mammals. The overarching goal of my research group is to understand the contribution of alternative splicing and the underlying RNA-regulatory networks in the brain and brain-related disorders. Previous work from multiple groups, including ours, unambiguously demonstrated that the brain has unique splicing-regulatory programs compared to non-neuronal tissues. Our studies also revealed the establishment of a pan-neuronal splicing program regulated by multiple RNA-binding proteins (RBPs) during neural development, and demonstrated the important role of the Rbfox protein family in regulating axonal maturation and neuronal excitability. However, how alternative splicing contributes to the distinct molecular profiles of diverse neuronal cell types in the cortex is currently poorly understood. We hypothesize that the transcriptome diversity generated by highly regulated alternative exons is a major component that specifies neuronal cell type identity and function. In this application, we describe our preliminary analysis of neuronal cell type-specific alternative splicing regulation in mouse cortex, which provides strong support for the following specific aims we would like to pursue: 1) Perform systematic analysis of neuronal cell type-specific alternative splicing to identify novel neuronal subclasses and regulators using deep sc-RNA-seq data. 2) Validate our computational predictions and characterize mechanisms of neuronal cell type-specific splicing regulation and function using two complementary model systems: the distinction of two major subclasses of GABAergic interneurons originating from caudal (CGE) and medial (MGE) ganglionic eminences, and a GABAergic neuron- specific microexon in Ank3/Ankyrin G. To achieve our goal, we will use a multidisciplinary approach that integrates cutting-edge statistical an machine learning methods and multiple in vitro and in vivo experimental models. This study will generate a global and mechanistic view of precise alternative splicing regulation across diverse neuronal cell types and illuminate its impact on neuronal structural and functional properties.
项目总结

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Chaolin Zhang其他文献

Chaolin Zhang的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Chaolin Zhang', 18)}}的其他基金

Mapping proximal and distal splicing-regulatory elements
绘制近端和远端剪接调控元件
  • 批准号:
    10658516
  • 财政年份:
    2023
  • 资助金额:
    $ 62.5万
  • 项目类别:
Complexity and evolution of splicing-regulatory networks
剪接调控网络的复杂性和演化
  • 批准号:
    10799138
  • 财政年份:
    2023
  • 资助金额:
    $ 62.5万
  • 项目类别:
Complexity and evolution of splicing-regulatory networks
剪接调控网络的复杂性和演化
  • 批准号:
    10406411
  • 财政年份:
    2022
  • 资助金额:
    $ 62.5万
  • 项目类别:
Mapping proximal and distal splicing-regulatory elements
绘制近端和远端剪接调控元件
  • 批准号:
    10669332
  • 财政年份:
    2022
  • 资助金额:
    $ 62.5万
  • 项目类别:
Complexity and evolution of splicing-regulatory networks
剪接调控网络的复杂性和演化
  • 批准号:
    10706471
  • 财政年份:
    2022
  • 资助金额:
    $ 62.5万
  • 项目类别:
RNA Regulatory Networks in Neuronal Cell Type Diversity and Function
神经元细胞类型多样性和功能中的 RNA 调控网络
  • 批准号:
    10816681
  • 财政年份:
    2022
  • 资助金额:
    $ 62.5万
  • 项目类别:
Integrative analysis of tissue-specific alternative splicing regulation under adaptive selection
适应性选择下组织特异性选择性剪接调控的综合分析
  • 批准号:
    10402926
  • 财政年份:
    2021
  • 资助金额:
    $ 62.5万
  • 项目类别:
RNA Regulatory Networks in Neuronal Cell Type Diversity and Function
神经元细胞类型多样性和功能中的 RNA 调控网络
  • 批准号:
    10531908
  • 财政年份:
    2021
  • 资助金额:
    $ 62.5万
  • 项目类别:
CLIP Tool Kit (CTK): pipeline, user interface and tutorials for CLIP data analysis
CLIP 工具套件 (CTK):用于 CLIP 数据分析的管道、用户界面和教程
  • 批准号:
    9294442
  • 财政年份:
    2017
  • 资助金额:
    $ 62.5万
  • 项目类别:
Systematic functional dissection of neuronal transcriptome diversity
神经元转录组多样性的系统功能剖析
  • 批准号:
    9272022
  • 财政年份:
    2016
  • 资助金额:
    $ 62.5万
  • 项目类别:

相似海外基金

Kilohertz volumetric imaging of neuronal action potentials in awake behaving mice
清醒行为小鼠神经元动作电位的千赫兹体积成像
  • 批准号:
    10515267
  • 财政年份:
    2022
  • 资助金额:
    $ 62.5万
  • 项目类别:
Signal processing in horizontal cells of the mammalian retina – coding of visual information by calcium and sodium action potentials
哺乳动物视网膜水平细胞的信号处理 â 通过钙和钠动作电位编码视觉信息
  • 批准号:
    422915148
  • 财政年份:
    2019
  • 资助金额:
    $ 62.5万
  • 项目类别:
    Research Grants
CAREER: Resolving action potentials and high-density neural signals from the surface of the brain
职业:解析来自大脑表面的动作电位和高密度神经信号
  • 批准号:
    1752274
  • 财政年份:
    2018
  • 资助金额:
    $ 62.5万
  • 项目类别:
    Continuing Grant
Development of Nanosheet-Based Wireless Probes for Multi-Simultaneous Monitoring of Action Potentials and Neurotransmitters
开发基于纳米片的无线探针,用于同时监测动作电位和神经递质
  • 批准号:
    18H03539
  • 财政年份:
    2018
  • 资助金额:
    $ 62.5万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Population Imaging of Action Potentials by Novel Two-Photon Microscopes and Genetically Encoded Voltage Indicators
通过新型双光子显微镜和基因编码电压指示器对动作电位进行群体成像
  • 批准号:
    9588470
  • 财政年份:
    2018
  • 资助金额:
    $ 62.5万
  • 项目类别:
Enhanced quantitative imaging of compound action potentials in multi-fascicular peripheral nerve with fast neural Electrical Impedance Tomography enabled by 3D multi-plane softening bioelectronics
通过 3D 多平面软化生物电子学实现快速神经电阻抗断层扫描,增强多束周围神经复合动作电位的定量成像
  • 批准号:
    10009724
  • 财政年份:
    2018
  • 资助金额:
    $ 62.5万
  • 项目类别:
Enhanced quantitative imaging of compound action potentials in multi-fascicular peripheral nerve with fast neural Electrical Impedance Tomography enabled by 3D multi-plane softening bioelectronics
通过 3D 多平面软化生物电子学实现快速神经电阻抗断层扫描,增强多束周围神经复合动作电位的定量成像
  • 批准号:
    10467225
  • 财政年份:
    2018
  • 资助金额:
    $ 62.5万
  • 项目类别:
Fast high-resolution deep photoacoustic tomography of action potentials in brains
大脑动作电位的快速高分辨率深度光声断层扫描
  • 批准号:
    9423398
  • 财政年份:
    2017
  • 资助金额:
    $ 62.5万
  • 项目类别:
NeuroGrid: a scalable system for large-scale recording of action potentials from the brain surface
NeuroGrid:用于大规模记录大脑表面动作电位的可扩展系统
  • 批准号:
    9357409
  • 财政年份:
    2016
  • 资助金额:
    $ 62.5万
  • 项目类别:
Noval regulatory mechanisms of axonal action potentials
轴突动作电位的新调节机制
  • 批准号:
    16K07006
  • 财政年份:
    2016
  • 资助金额:
    $ 62.5万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了