Whole genome screen for novel regulators of tissue homeostasis and regeneration

描述(由申请人提供)：用于组织内稳态和再生的新调节剂的全基因组筛选是一个解决人类健康问题的模型系统。众所周知，行星动物有能力从自己身体的碎片中再生出完整的动物。随着最近的研究表明，稻瘟病菌能够适应现代细胞、分子和RNAi技术，它正在成为解决在果蝇或秀丽线虫中不容易研究的研究问题的模式生物，包括成年组织的伤口愈合、再生、体细胞干细胞和组织动态平衡。2007年，我们对地中海链霉菌基因组进行了注释，并构建了一个公开可用的基因组数据库SmedGD，其中包含了基因模型。这笔赠款的目标是在高通量的基于图像的筛选中使用地中海链球菌的基因注释，以获得组织再生和动态平衡的新调节器。为此，我们将(1)使用一系列分子和免疫学技术，包括全基因组RNAi屏幕，以及(2)利用现有的图像处理、管理和注释工具来构建一个既能支持我们的实验又能将我们的结果分发给科学界的网络基础设施。 与公共卫生相关：该项目将使用已测序的稻纵卷蛾基因组来寻找与组织维护和再生有关的基因。该项目采用了许多令人兴奋的新技术，包括RNA干扰、自动共聚焦显微镜以及图像处理和注释工具来实现其目标。由于我们将限制我们的筛选具有真正的人类同源基因的脊椎动物基因，任何获得的干细胞功能缺陷表型都将成为研究人类干细胞功能、再生和伤口愈合的潜在模型，有效地推动在这些人类健康前沿的努力。

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.