A Resource Center for Tetrahymena Thermophila

描述（由申请人提供）：本提案旨在为康奈尔大学四膜虫库存中心寻求持续的资金，以维持其目前的运营并扩大其作为整个社区资源的能力。嗜热四膜虫是真核细胞和分子生物学的一个关键模型，它有助于我们理解与人类疾病直接相关的一系列生物现象，包括癌症、不孕症和神经元功能障碍。四膜虫也显示出作为蛋白质生产平台的巨大希望，包括生产流感、疟疾和其他传染原的疫苗。具体来说，我们的目标是1)完成获得遗传上不同的菌株的优秀集合，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；3)将斯坦福大学的孤儿四膜虫基因组数据库（TGD）与四膜虫库存中心（Tetrahymena Stock Center）合并，实现品系信息与基因组水平信息的整合。通过库存中心运营TGD，并将这些努力与社区注释联系起来，不仅支持了中心的使命，而且由于TGD不再被积极维护，因此为整个社区带来了显著的附加值。最后，作为Stock Center研究的一部分，我们将4)利用四膜虫几乎完整的宏核基因组序列来绘制大量现有的微核缺失，并继续努力将Cre-lox技术应用于该系统，以完成覆盖所有5条微核染色体的综合绘制面板的构建。该小组将作为一个支架，在其上可以快速对齐遗传和分子标记，并将有力地支持目前正在进行的嗜热t细胞的许多功能基因组研究。由于四膜虫独特的二态核结构，创造可行的、几乎任何大小的纯合缺失的能力是唯一可能的，这代表了这种重要模式生物的许多新特征之一。

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supports the mission of the Center, but represents a significant value added for the community as a whole since TGD is no longer actively maintained.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.