Transmission of Prions Within and Between Species

简介（由申请人提供）：研究计划：传染性海绵状脑病（TSE）是一组慢性且致命的神经退行性疾病。慢性消耗性疾病（CWD）是发生在野生和圈养麋鹿、骡鹿和白尾鹿中的一种TSE。经口传播已在许多TSE病例中得到记录，并在给予CWD感染材料的鹿中实验重现。CWD经口传播给其他物种的可能性仍不确定。CWD的潜在宿主包括食用鹿肉、野生食肉动物和农业上重要的反刍动物的人类。影响TSE易感性的遗传多态性已经在一些物种中被发现，并可能影响CWD的传播。我将在转基因模型中测试CWD的口腔感染性，以确定氨基酸多态性对疾病易感性的影响。我将在一个天然的TSE宿主中测试口腔传染性，以进一步确定TSE在物种间的宿主范围。由于CWD阳性动物的地理分布，以及有证据表明牛海绵状脑病（影响牛的TSE）具有人畜共患的潜力，这些研究是及时和有针对性的。

DESCRIPTION (provided by applicant): Research Proposal: Transmissible Spongiform Encephalopathies (TSE) are a group of chronic invariably fatal neurodegenerative diseases. Chronic Wasting Disease (CWD) is a form of TSE in wild and captive elk, mule deer, and white tail deer. Oral transmission has been documented in many TSE's, and has been experimentally reproduced in deer given CWD infectious material. The oral transmissibility of CWD to other species remains uncertain. Potential hosts for CWD includehumans that consume venison, wild carnivores, and agriculturally important ruminants. Genetic polymorphismsthat effect TSE susceptibility have been identified for some species and may effect transmission of CWD. I will test the oral infectivityof CWD in a transgenic model to determine the effect of an amino acid polymorphism on disease susceptibility. I will test oral infectivity in a natural TSE host to further define the host range of TSE between species. Such studies are timely and topical due to the geographic spread of CWD positive animals and evidence that Bovine Spongiform Encephalopathy, the TSE affecting cattle, has zoonotic potential. The Candidate: The candidate is a veterinarian who has recently completed a residency in Comparative Medicine at the University of Washington School of Medicine. He has matriculated into the Washington State University Department of Veterinary Microbiology and Pathology for additional research training to culminate in the Doctor of Philosophy degree. The continuation of mentored training in biomedical research, with particular emphasis on continued investigation into the pathogenesis of TSE's, is necessary for development as an independent and collaborative investigator. The Environment: The research project will create a unique collaborative opportunity drawing on the resources and relevant expertise of both Washington State University and the University of Washington. Washington State University will provide interaction with internationally recognized faculty who have expertise in the study of Transmissible Spongiform Encephalopathies. The University of Washington and associated Comparative Medicine Transgenic Resource Laboratory will provide interaction with faculty and staff who have extensive experience in transgenic technology and the use of mutant mice in modern biomedical research. Both universities have established educational programs with a productive history of training veterinarians in biomedical research. Activities include weekly literature review, clinical-pathologic conferences, and research seminars. Participation in educational and training opportunities from these multiple sources will provide Dr. Harrington with a well rounded scientific background and allow specific research training pertinent to his area of research interest.