EPH-RECEPTOR SIGNALING IN LENS DEVELOPMENT AND AGING

晶状体发育和老化中的 EPH 受体信号传导

基本信息

批准号：
9310254
负责人：
Alan Shiels
金额：
$ 34.2万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-08-01 至 2019-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9310254
关键词：
Aging Alleles Architecture Biological Process Blindness Cataract Cells Childhood Code Collaborations Complex Crystalline Lens Development EPHA2 gene Embryonic Development Environment Environmental Risk Factor Eph Family Receptors Ephrins Face Family Frequencies Functional disorder Gene Targeting Genes Genetic Variation Germ Lines Giant Cells Goals Human Image Imaging Techniques Immunologic Surveillance Impairment Inherited Interdisciplinary Study Knock-in Mouse Knockout Mice Lens Fiber Lens development Link Mass Spectrum Analysis Membrane Modeling Molecular Molecular Genetics Mus Mutant Strains Mice Mutation Optics Pathogenicity Pathologic Processes Phenotype Phosphorylation Prevalence Property Proteolytic Processing Proteome Proteomics Receptor Protein-Tyrosine Kinases Receptor Signaling Reporter Research Role Signal Transduction Site Sunlight Surgical sutures Techniques Testing Transgenic Organisms Ultraviolet B Radiation Universities Untranslated RNA Variant Virus Diseases Visual impairment age related base case control cohort comparative congenital cataract fiber cell gain of function insight interdisciplinary approach lens lens transparency loss of function member mutant next generation sequencing protein function protein protein interaction public health relevance receptor risk variant signal processing targeted sequencing tissue regeneration tumor progression

项目摘要

DESCRIPTION (provided by applicant): EPH-receptor tyrosine kinases activate complex signaling networks involved in diverse biological and pathological processes including embryonic development, tissue regeneration, immune surveillance, tumor progression and viral infection. Recently, variations in the gene encoding one of these receptors, EPHA2, have been associated with inherited and age-related forms of human cataract, and EPHA2 has been identified as an abundant, but poorly understood, component of the lens membrane proteome. The overall goal of this research is to advance understanding of EPH-receptor signaling in lens development and aging. In this proposal we will conduct an interdisciplinary approach to elucidate molecular mechanisms that connect genetic variation in EPHA2 with lens phenotype. First, we will perform targeted-sequencing to determine the relationship between EPHA2 coding variation and lens aging. Second, we will use gene-targeted mice and imaging techniques to characterize EPHA2 function and dysfunction during lens development. Finally we will undertake proteomics techniques to characterize EPHA2 signaling and processing in the lens. Results from these studies will provide new insights regarding the role of EPH-receptor signaling in lens development and aging, within the context of cataract formation - an important cause of visual impairment.

描述（由申请人提供）：EPH 受体酪氨酸激酶激活涉及多种生物和病理过程的复杂信号网络，包括胚胎发育、组织再生、免疫监视、肿瘤进展和病毒感染。最近，编码这些受体之一的基因 EPHA2 的变异与人类白内障的遗传性和年龄相关形式有关，并且 EPHA2 已被确定为晶状体膜蛋白质组中丰富但知之甚少的成分。这项研究的总体目标是增进对晶状体发育和衰老过程中 EPH 受体信号传导的了解。在本提案中，我们将采用跨学科方法来阐明将 EPHA2 遗传变异与晶状体表型联系起来的分子机制。首先，我们将进行靶向测序以确定 EPHA2 编码变异与镜片老化之间的关系。其次，我们将使用基因靶向小鼠和成像技术来表征晶状体发育过程中 EPHA2 的功能和功能障碍。最后，我们将采用蛋白质组学技术来表征晶状体中的 EPHA2 信号传导和处理。这些研究的结果将提供关于 EPH 受体信号传导在晶状体发育和衰老中的作用的新见解，以及白内障形成的背景——白内障是视力障碍的一个重要原因。