Genetic analysis of nematode cell differentiation

线虫细胞分化的遗传分析

• 批准号: 8081140
• 负责人: MARTIN CHALFIE
• 金额: $ 19.69万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8081140
• 关键词: Affect; Afferent Neurons; Alleles; Binding; Biological; Blood Pressure; Caenorhabditis elegans; Cell Differentiation process; Cell physiology; Cells; Cholesterol; Cholesterol Homeostasis; Collection; Complex; Development; Disease; Extracellular Matrix; Extracellular Matrix Proteins; Fatty Acids; Funding; Gene Expression; Generations; Genes; Genetic; Goals; Grant; Growth; Health; Human; Human Biology; Individual; Inherited; Knowledge; Label; Length; Lipid Bilayers; Lipid Binding; Maintenance; Mechanics; Membrane Lipids; Methods; Microtubules; Mitotic; Modification; Molecular Genetics; Molecular Models; Motor Neurons; Muscle; Nematoda; Nerve; Nervous system structure; Neuronal Differentiation; Neurons; Organism; Pattern; Process; Production; Proteins; RNA; RNA Interference; RNA-Binding Proteins; Regulation; Research; Research Personnel; Role; Sensory; Signal Transduction; Site; Subcutaneous Tissue; Temperature; Testing; Time; Touch sensation; base; cell type; genetic analysis; killings; member; molecular modeling; neuron development; protein complex; public health relevance; receptor; research study; transcription factor

DESCRIPTION (provided by applicant): We will continue our study of genes needed for neuronal differentiation and function in the nematode Caenorhabditis elegans. Most of the research will center, as in the past, on the analysis of the development and activity of the six touch receptor neurons (TRNs). Previous research under this grant has identified genes needed for the generation, specification, maintenance and function of the TRNs. In particular in the last funding period we enlarged the collection of TRN-expressed genes 8-fold to approximately 200 genes, identified components that restrict TRN development to six cells, and identified the transduction complex that sense touch in these cells. This last complex is the first transduction complex to be identified in any eukaryotic mechanosensory neuron. We also developed several new methods that we will exploit in the upcoming funding period. In particular we will investigate how cell fate is determined and maintained and how the lipid bilayer and extracellular matrix affect mechanosensation. The specific aims of the proposal are: 1) to investigate the regulation of post-mitotic gene expression, particular examining how genes needed only early in development of neurons are turned off; 2) to investigate the basis of cell-type specification within the TRNs; 3) to characterize lipid- binding and modulating components of the MEC-4 channel complex and similar proteins; and 4) to investigate the role of the extracellular matrix (ECM) in touch sensitivity. A secondary consequence of the proposed experiments will be the discovery a wealth of genes needed for general development and function of the C. elegans nervous system. PUBLIC HEALTH RELEVANCE: We study the genetic control of nerve cell development and function of touch sensory cells in the nematode Caenorhabditis elegans. Many of the genes we study have counterparts in humans (some being the basis of inherited diseases), but we can study their function much better in this organism. By identifying molecules needed for nerve growth and mechanosensitivity, we gain basic knowledge that is useful in the general understanding of human biology and health, as evident, e.g., by researchers studying the sensing of blood pressure using our molecular models to guide their research.

描述（由申请人提供）：我们将继续我们的研究所需的基因神经元分化和功能的线虫线虫小杆线虫。与过去一样，大部分研究将集中在对六个触觉受体神经元（TRN）的发育和活动的分析上。根据这项资助，以前的研究已经确定了TRN的生成，规范，维护和功能所需的基因。特别是在上一个资助期，我们将TRN表达基因的集合扩大了8倍，达到约200个基因，鉴定了限制TRN发育到6个细胞的组分，并鉴定了在这些细胞中感知触摸的转导复合物。最后一个复合物是在任何真核机械感觉神经元中鉴定的第一个转导复合物。我们还开发了几种新方法，我们将在即将到来的资助期内利用这些方法。特别是，我们将研究细胞的命运是如何确定和维持，以及脂质双层和细胞外基质如何影响机械感觉。该提案的具体目的是：1）研究有丝分裂后基因表达的调节，特别是研究仅在神经元发育早期需要的基因如何被关闭; 2）研究TRN内细胞类型特化的基础; 3）表征MEC-4通道复合物和类似蛋白质的脂质结合和调节组分;（4）探讨细胞外基质（ECM）在触觉敏感性中的作用。拟议实验的第二个结果将是发现大量的基因，这些基因是C。线虫的神经系统 公共卫生相关性：我们研究线虫线虫的神经细胞发育的遗传控制和触觉感觉细胞的功能。我们研究的许多基因在人类中都有对应的基因（有些是遗传性疾病的基础），但我们可以更好地研究它们在这种生物体中的功能。通过鉴定神经生长和机械敏感性所需的分子，我们获得了对人类生物学和健康的一般理解有用的基本知识，如明显的，例如，研究人员使用我们的分子模型来指导他们的研究。