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supports the mission of the Center, but represents a significant value added for the community as a whole since TGD is no longer actively maintained.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