A Resource Center for Tetrahymena Thermophila

描述（由申请人提供）：本提案寻求继续资助康奈尔大学的四膜虫种群中心，以维持其目前的运作，并扩大其作为整个社区资源的能力。作为真核细胞和分子生物学的重要模型，嗜热四膜虫有助于我们理解与人类疾病（包括癌症、不育和神经元功能障碍）直接相关的广泛生物现象。四膜虫作为蛋白质制造的平台也显示出巨大的前景，包括生产流感，疟疾和其他传染病的疫苗。具体来说，我们的目标是：1）完成对遗传上不同菌株的优秀收藏品的收购，并接受新开发的菌株; 2）在我们现有的设施中保持遗传库存，并通过我们简单的基于网络的订购系统向科学界提供这些库存; 3）合并孤儿四膜虫基因组数据库（TGD）在斯坦福大学与四膜虫库存中心合作，以便在基因组水平上整合菌株信息。通过库存中心使TGD运行，并将这些努力与社区注释联系起来，不仅支持中心的使命，而且代表了整个社区的重要附加值，因为TGD不再积极维护。最后，作为库存中心研究部分的一部分，我们将4）使用四膜虫几乎完整的大核基因组序列来绘制大量现有的微核缺失，并继续努力使Cre-lox技术适应该系统，以完成跨越所有五个微核染色体的综合绘图面板的构建。该基因组将作为一个支架，在其上可以快速比对遗传和分子标记，并将有力地支持目前正在进行的T。嗜热菌创建几乎任何大小的可行的纯合缺失的能力是唯一可能的，这是由于四膜虫独特的二态核结构，并代表了这种重要模式生物的许多新特征之一。 公共卫生相关性（由申请人提供）：本项目将支持使用嗜热四膜虫作为基础和应用研究的工具。这种生物体是我们理解癌症、生育、衰老和正常脑功能所涉及的许多基本生物学过程的关键，并直接用作治疗人类疾病的疫苗和治疗性蛋白质的制造平台。

DESCRIPTION (provided by applicant): This proposal seeks continued funding for the Tetrahymena Stock Center at Cornell University in order to maintain its current operations and expand its capabilities as a resource for the community at large. A key model for eukaryotic cell and molecular biology, Tetrahymena thermophila has been instrumental to our understanding of a wide range of biological phenomena with direct relevance to human disease including cancer, infertility, and neuronal dysfunction. Tetrahymena has also shown great promise as a platform for protein manufacture including the production of vaccines for influenza, malaria and other infectious agents. Specifically, we aim to 1) complete the acquisition of outstanding collections of genetically distinct strains and accept newly developed strains as they arise; 2) maintain genetic stocks in our current facilities and make them available to the scientific community via our simple web-based ordering system; 3) merge the orphaned Tetrahymena Genome Database (TGD) at Stanford University with the Tetrahymena Stock Center in order to integrate strain information with information at the level of the genome. Making TGD operational through the Stock Center, and linking those efforts to community annotation, not only supports the mission of the Center, but represents a significant value added for the community as a whole since TGD is no longer actively maintained. Lastly, as part of the research component of the Stock Center, we will 4) use the nearly complete macronuclear genome sequence of Tetrahymena to map a large set of existing micronuclear deletions, and continue efforts to adapt the Cre-lox technology to this system in order to complete the construction of a comprehensive mapping panel that spans all five micronuclear chromosomes. This panel will act as a scaffold on which genetic and molecular markers can be quickly aligned and will strongly support the many functional genomic studies now underway in T. thermophila. The ability to create viable, homozygous deletions of virtually any size is only possible due to the unique dimorphic nuclear structure of Tetrahymena and represents one of many novel features of this important model organism. PUBLIC HEALTH RELEVANCE (provided by applicant): This project will support the use of Tetrahymena thermophila as a tool for basic and applied research. This organism has been key to our understanding of many fundamental biological processes involved in cancer, fertility, aging and normal brain function, and has direct applications as a manufacturing platform for vaccines and therapeutic proteins for the treatment of human disease.