TRANSGENIC TOOLS FOR NEMATODES

描述（由申请人提供）： 现代生物学研究非常依赖转基因工具。这是真实的，几乎所有的模型系统被用来探索各种各样的问题，从小鼠大脑发育的细胞生物学到人类病原体（如锥虫）的高度专业化的基于抗原变异的免疫防御。在过去的五年中，转座子和整合酶分子工程和重组DNA技术的快速发展导致了许多模式系统的复杂的转座子和整合酶为基础的转基因技术的发展。这些工具包括用于斑马鱼的高效转座子、用于果蝇的高效位点特异性整合系统以及用于小鼠的新一代基因组工程工具。这些进展尚未应用于所有共同模式系统。特别是，在转基因方法学上几乎没有改进。elegans模型系统。这些工具的开发对于利用已经致力于开发这种有前途的模型系统的大量遗传、分子和智力资源至关重要。这项拨款建议通过测试使用两个移动的遗传元件来创建转基因线虫的可行性来开发分子遗传资源。这些工具的效用将包括提高能力，创造突变研究基因功能，创造基因报告细胞生物学分析，并创造转基因动物的基础细胞过程的研究，许多人类疾病的原因。 公共卫生相关性：这项资助计划用于开发一种用于研究人类疾病基础细胞过程的模型系统的转基因工具。这个模型系统对理解疾病的贡献包括发现了几个生物过程，每个过程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起着关键作用。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（如由基因错误表达引起的癌症）的非常有前途的方法。基础研究，如本文所建议的工作，对公共卫生的长期进展至关重要。

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.