TRANSGENIC TOOLS FOR NEMATODES

线虫转基因工具

基本信息

批准号：
7471332
负责人：
MICHAEL L NONET
金额：
$ 19万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-04-01 至 2010-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7471332
关键词：
Antigenic Variation Apoptosis Basic Science Biological Biological Models Biological Process Biology Brain Caenorhabditis elegans Cell physiology Cells Cellular biology Commit Communities DNA Development Disease Drosophila genus Engineering Enhancers Gene Expression Generations Genetic Engineering Genome Genome engineering Grant Human Indium Insertional Mutagenesis Integrase Malignant Neoplasms Mediating Methodology Mobile Genetic Elements Molecular Molecular Genetics Mus Mutation Nematoda Nobel Prize Organism Phosphorus Play Process Public Health RNA Interference Reporter Genes Research Resources Rewards Risk Role Site Stroke System Techniques Technology Testing Transgenic Animals Transgenic Organisms Transposase Trypanosoma Visual Work Xenopus Zebrafish base design fly gene function genetic resource human disease improved pathogen recombinase research study response site-specific integration size tool tool development vector

项目摘要

DESCRIPTION (provided by applicant): Modern biology research relies extremely heavily on transgenic tools. This is true of virtually all model systems that are being used to explore questions as diverse as the cell biology of mouse brain development to the highly specialized antigenic variation-based immunological defenses of human pathogens like trypanosomes. In the last five years, rapid advances in transposon and integrase molecular engineering and recombinant DNA technology have led to the development of sophisticated transposon and integrase based transgenic techniques for many model systems. These tools include efficient transposons for zebrafish, efficient site- specific integration systems for Drosophila as well as a new generation of genome engineering tools for mice. These advances have not been applied to all common model systems. In particular, few improvements have been made in transgenic methodologies for the C. elegans model system. Development of these tools is critical to leveraging the substantial genetic, molecular, and intellectual resources that have already been committed to develop this promising model system. This grant proposes to develop molecular genetic resources by testing the feasibility of using two mobile genetic elements for creating transgenic nematodes. The utility of these tools will include the improved ability to create mutations to study gene function, to create gene reporters for cell biological analysis, and to create transgenic animals for the study of basic cellular processes that underlie the cause of many human diseases. Public Health Relevance: This grant proposes to develop transgenic tools for a model system used in the study of basic cellular processes that underlie human disease. The contributions of this model system to understanding disease include the discoveries of several biological processes each of which was recently recognized by a Nobel prize. The first discovery is that of programmed cell death which plays critical roles in cellular responses to stroke. The second is the discovery of the process of RNA interference that is widely recognized as very promising methodology to treat human diseases such as cancer that result from the mis-expression of genes. Basic research such as the work proposed herein is essential for long-term progress in public health.

描述（由申请人提供）：现代生物学研究极其依赖转基因工具。几乎所有用于探索各种问题的模型系统都是如此，从小鼠大脑发育的细胞生物学到人类病原体（如锥虫）高度专业化的基于抗原变异的免疫防御。在过去五年中，转座子和整合酶分子工程以及重组 DNA 技术的快速发展导致了许多模型系统的复杂的基于转座子和整合酶的转基因技术的发展。这些工具包括针对斑马鱼的高效转座子、针对果蝇的高效位点特异性整合系统以及针对小鼠的新一代基因组工程工具。这些进步尚未应用于所有常见模型系统。特别是，线虫模型系统的转基因方法几乎没有取得任何改进。这些工具的开发对于利用大量的遗传、分子和智力资源至关重要，这些资源已经致力于开发这个有前景的模型系统。该赠款提议通过测试使用两种移动遗传元件创建转基因线虫的可行性来开发分子遗传资源。这些工具的用途将包括提高创建突变以研究基因功能、创建用于细胞生物学分析的基因报告基因以及创建转基因动物以研究导致许多人类疾病的基本细胞过程的能力。公共健康相关性：这笔赠款提议为用于研究人类疾病的基本细胞过程的模型系统开发转基因工具。该模型系统对理解疾病的贡献包括发现了几种生物过程，其中每一个最近都获得了诺贝尔奖。第一个发现是程序性细胞死亡，它在细胞对中风的反应中发挥着关键作用。第二个是RNA干扰过程的发现，该过程被广泛认为是治疗人类疾病（例如由基因错误表达引起的癌症）非常有前途的方法。本文提出的基础研究对于公共卫生的长期进展至关重要。