Whole genome screen for novel regulators of tissue homeostasis and regeneration

描述（由申请人提供）：组织稳态和再生的新型调节剂的全基因组筛选Schmidtea medialacea是用于解决人类健康问题的模型系统。Planarians以其从身体碎片再生完整动物的能力而闻名。在最近的示威活动之后，S。由于地中海果蝇适合于现代细胞、分子和RNAi技术，它正在成为解决在果蝇或秀丽隐杆线虫中不能容易地研究的研究问题的首选模式生物，包括成体组织的伤口愈合、再生、体干细胞和组织稳态。2007年，我们对S. media.media.media.media.media.media.media.media.media.media.media.media.media.media.media.media.media.media.media.media.media.media.media.media.media.media.media.media.media.media.该补助金的目的是使用S。在一个高通量的基于图像的筛选组织再生和稳态的新的监管机构mediopreea基因注释。为此，我们将（1）采用一系列分子和免疫学技术，包括全基因组RNAi筛选，以及（2）利用现有的图像处理，管理和注释工具来构建一个网络基础设施，既可以支持我们的实验，又可以将我们的结果分发给科学界。 公共卫生相关性：该项目将使用已测序的涡虫Schmidtea mediterranea的基因组来寻找与组织维持和再生有关的基因。该项目采用了许多令人兴奋的新技术，包括RNA干扰，自动共聚焦显微镜，图像处理和注释工具，以实现其目标。因为我们将我们的筛选限制在真正的人类同源基因的真涡虫基因上，所以获得的任何干细胞功能缺陷表型都成为研究人类干细胞功能、再生和伤口愈合的潜在模型，有效地推进了人类健康这些前沿领域的努力。

DESCRIPTION (provided by applicant): Whole genome screen for novel regulators of tissue homeostasis and regeneration Schmidtea mediterranea is a model system for addressing human health issues. Planarians are well known for their ability to regenerate complete animals from fragments of their bodies. Following recent demonstrations that S. mediterranea is amenable to modern cell, molecular, and RNAi techniques, it is becoming the model organism of choice for addressing research questions that cannot be easily studied in Drosophila melanogaster or Caenorhabditis elegans, including wound healing of adult tissues, regeneration, somatic stem cells, and tissue homeostasis. In 2007 we annotated the S. mediterranea genome and constructed a publicly available genome database, SmedGD containing the gene models. The objective of this grant is to use the S. mediterranea gene annotations in a high-throughput image-based screen for novel regulators of tissue regeneration and homeostasis. Toward this end we will (1) employ a battery of molecular and immunological techniques, including a genome-wide RNAi screen, and (2) leverage existing image processing, management and annotation tools to construct a cyberinfrastructure that can both support our experiments and distribute our results to the scientific community. PUBLIC HEALTH RELEVANCE: This project will use the sequenced genome of the planarian Schmidtea mediterranea to search for genes involved in tissue maintenance and regeneration. The project employs a number of exciting new technologies, including RNA interference, an automated confocal microscope, and image processing and annotation tools to achieve its aims. Because we will restrict our screen to planarian genes with bona fide human homologs, any stem cell function deficiency phenotype obtained becomes a potential model to study human stem-cell function, regeneration and wound healing, effectively advancing efforts in these frontiers of human health.