This proposal seeks continued funding for the Tetrahymena Stock Center and ancillary Tetrahymena Genome Database (TGD) in order to maintain their current operations and expand their capabilities as resources 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 health and disease including cancer, infertility, aging, and neuroendocrine 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) maintain genetic stocks in our current facilities and make them available to the scientific community via our simple web-based ordering system; 2) expand the current collection and complete annotation of existing strains; 3) extend the Center's services to include storage and dissemination of useful plasmid constructs, and a new fee-based transformation service that will significantly increase cost recovery; 4) offer short techniques an methodology training sessions to promote the use of Tetrahymena by investigators who are new to the system; 5) promote continued community-based annotation of the Tetrahymena macronuclear genome via the TGD Wiki; 6) establish links between individual strains in the Stock Center collection and relevant gene pages in TGD to simplify identification of useful strains and improve information access for the Center's users. Lastly, as part of the research component of the Stock Center, we will 7) create more efficient strategies for micronuclear transformation and utilize these to generate a panel of small, targeted deletions in 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 neuroendocrine function, and has direct applications as a manufacturing platform for vaccines and therapeutic proteins for the treatment of human disease.
| Pinello, Jennifer Fricke; Lai, Alex L; Millet, Jean K et al. (2017) Structure-Function Studies Link Class II Viral Fusogens with the Ancestral Gamete Fusion Protein HAP2. Curr Biol 27:651-660 |
| Cole, Eric S; Cassidy-Hanley, Donna; Fricke Pinello, Jennifer et al. (2014) Function of the male-gamete-specific fusion protein HAP2 in a seven-sexed ciliate. Curr Biol 24:2168-2173 |
