Mapping Cerebellar Development in Time and Space

绘制小脑发育的时间和空间图

基本信息

批准号：
7449641
负责人：
KRISTIN M HAMRE
金额：
$ 75.68万
依托单位：
UNIVERSITY OF TENNESSEE HEALTH SCI CTR
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-09-05 至 2010-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7449641
关键词：
Adult Affect Anatomy Autistic Disorder Bayesian Method Behavior Binding Sites Bioinformatics Biological Brain Brain region Cell Communication Cell Count Cell model Cell physiology Cells Cellular biology Cerebellar Diseases Cerebellum Cessation of life Childhood Cognitive Communities Condition Control Locus Data Data Analyses Data Set Databases Development Developmental Process Disease Equation Funding Gene Expression Gene Mutation Genes Genetic Models Genetic Transcription Goals Grant Graph Health Sciences Housing Human Image Imagery In Situ Hybridization Inbred Mouse Informatics Link Magnetic Resonance Imaging Malignant neoplasm of brain Maps Modeling Molecular Molecular Analysis Molecular Profiling Morphogenesis Motor Mus Mutant Strains Mice Neuraxis Neurophysiology - biologic function Nodal Online Systems Pathway interactions Pattern Personal Satisfaction Phenotype Purpose Quantitative Trait Loci Recombinant Inbred Strain Recombinants Research Research Personnel Resources Reverse Transcriptase Polymerase Chain Reaction Role Schizophrenia Science Semantics Series Small Interfering RNA Source Space Models System Techniques Tennessee Testing Time Title Universities Validation Variant abstracting animation assay development base cell type computer based statistical methods data mining day design granule cell heuristics immunocytochemistry indexing knowledge base mouse genome mutant postnatal programs tool vector web-accessible

项目摘要

DESCRIPTION (provided by applicant): The cerebellum is emerging as an important brain region for the coordination of motor and cognitive behaviors. Developmental abnormalities of the cerebellum have been linked to autism, schizophrenia, and other disorders of human neural function. This grant proposes to acquire extensive new data sets for gene expression and cellular phenotypes over six epochs of cerebellar development in over 30 recombinant inbred (RI) strains of mice (BXD) and 15 single gene mutant mice. This data will be web-accessible via WebQTL. We will also develop and integrate web-based informatic and visualization tools for researchers to analyze our data sets, provide datasets of their own for analysis, and test hypotheses about the cellular and molecular development of the cerebellum. Four specific aims are proposed that will be supported by four core functions. In Aim 1, we will obtain the phenotypic data on the full spectrum of expressed genes and several quantifiable developmental processes in RI and mutant mice. This data will be integrated into a current database that houses an exceptional array of phenotypic data on the adult mouse brain, WebQTL. In Aim 2, we will use WebQTL, Bayesian method analysis, graph theoretical approaches to the identification of cliques in expression data, and latent semantic indexing of Medline references to mine data on the patterns, both in time and space, of expressed genes and cellular phenotypes. In Aim 3, we will use molecular (qRT-PCR), anatomical (in situ hybridization and immunocytochemistry) and experimental (siRNA) approaches to validate inferences about gene and phenotype relationships. Finally, in Aim 4, we will develop a web-accessible, 3D, high-end animation of the developing cerebellum that will be used for heuristic and experimental purposes. The data that is obtained and the tools that are constructed in this project will be fully open to the research community. This project is also designed to interface with several of the currently funded Human Brain Projects that look at the anatomy and cell biology of the adult mouse brain and cerebellum. The phenotypic data that is gathered will contribute to the growing understanding of the molecular and cellular bases of cerebellar development. Such information may help understand and treat disorders of cerebellar origin, such as the most common form of childhood brain cancer, the medullablastoma, which is believed to emanate from the developing granule cells of the cerebellum. In the long term, we hope to use the tools developed in this project to make predictions about the molecular pathways and cellular programs that are important to the well-being of the central nervous system

描述（由申请人提供）：小脑正在成为运动和认知行为协调的重要大脑区域。小脑的发育异常与自闭症，精神分裂症和其他人类神经功能的其他疾病有关。该赠款建议在30多个重组近交（RI）小鼠（BXD）和15个单基因突变小鼠的30多个小脑发育时期的六个时期的基因表达和细胞表型中获取广泛的新数据集。通过WebQTL，该数据将可以通过Web访问。我们还将开发和整合基于Web的信息和可视化工具，以供研究人员分析我们的数据集，提供其自己的数据集以进行分析，并检验有关小脑细胞和分子开发的假设。提出了四个特定目标，这些目标将由四个核心功能支持。在AIM 1中，我们将获得有关RI和突变小鼠的全部表达基因以及几个可量化的发育过程的表型数据。该数据将集成到当前数据库中，该数据库包含成年小鼠大脑的特殊表型数据，WebQTL。在AIM 2中，我们将使用WebQTL，贝叶斯方法分析，图理论方法来识别表达数据中的集团，以及在表达基因和细胞表型的时间和空间上对MEDLINE对地雷数据的潜在语义索引。在AIM 3中，我们将使用分子（QRT-PCR），解剖学（原位杂交和免疫细胞化学）和实验（SIRNA）方法来验证有关基因和表型关系的推论。最后，在AIM 4中，我们将开发一个可用于启发式和实验目的的开发小脑的可访问，3D，高端动画。该项目中获得的数据和构建的工具将完全向研究社区开放。该项目还旨在与几个目前资助的人脑项目互动，这些项目研究了成年小鼠脑和小脑的解剖学和细胞生物学。收集的表型数据将有助于对小脑发育的分子和细胞碱基的日益了解。这些信息可能有助于理解和治疗小脑起源的疾病，例如儿童脑癌最常见的形式，髓质瘤，据信它会从小脑的发育中的颗粒细胞中散发出来。从长远来看，我们希望使用该项目中开发的工具来预测有关中枢神经系统福祉至关重要的分子途径和细胞程序