Genetic analysis of nematode cell differentiation

线虫细胞分化的遗传分析

基本信息

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
项目类别：
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

项目摘要

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）：我们将继续研究线虫秀丽隐杆线虫中神经元分化和功能所需的基因。与过去一样，大多数研究都将集中在分析六个触摸受体神经元（TRN）的发育和活动上。该赠款的先前研究已经确定了TRN的生成，规范，维护和功能所需的基因。特别是在最后一个资金期间，我们扩大了TRN表达的基因8倍至大约200个基因的收集，确定了将TRN发育限制为六个细胞的成分，并确定了这些细胞中感接触的转导复合物。最后一个复合物是在任何真核机械感觉神经元中要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金期间利用这些方法。特别是我们将研究细胞命运的确定和维持，以及脂质双层和细胞外基质如何影响机械敏化。该提案的具体目的是：1）研究有丝分裂后基因表达的调节，特别是研究了仅在神经元发展中需要的基因才能关闭； 2）研究TRN中细胞类型规范的基础； 3）表征MEC-4通道复合物和相似蛋白的脂质结合和调节成分； 4）研究细胞外基质（ECM）在触摸灵敏度中的作用。提出的实验的次要结果将是发现秀丽隐杆线虫神经系统一般发展和功能所需的大量基因。公共卫生相关性：我们研究了线虫秀丽隐杆线虫中神经细胞发展和触摸感觉细胞功能的遗传控制。我们研究的许多基因在人类中都有对应物（有些是遗传疾病的基础），但是我们可以在这种生物体中更好地研究它们的功能。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础知识，例如，通过研究人员使用我们的分子模型来指导他们的研究来研究血压。