Transmission of Prions Within and Between Species

描述（由申请方提供）：研究方案：传染性海绵状脑病（TSE）是一组慢性、致死性神经退行性疾病。慢性消耗性疾病（CWD）是野生和圈养麋鹿、骡鹿和白色尾鹿中TSE的一种形式。在许多TSE中已经记录了口腔传播，并且已经在给予CWD感染性材料的鹿中实验性重现。CWD对其他物种的经口传播性仍然不确定。慢性消耗病的潜在宿主包括食用鹿肉的人类、野生食肉动物和农业上重要的反刍动物。影响TSE易感性的遗传多态性已被确定为某些物种，并可能影响CWD的传播。我将在转基因模型中测试慢性消耗病的口服感染性，以确定氨基酸多态性对疾病易感性的影响。本人将在天然TSE宿主中检测经口感染性，以进一步确定种属间TSE的宿主范围。由于CWD阳性动物的地理分布以及牛海绵状脑病（影响牛的TSE）具有人畜共患潜力的证据，此类研究是及时和局部的。 候选人：候选人是一名兽医，最近在华盛顿大学医学院完成了比较医学的住院医师培训。他被华盛顿州立大学兽医微生物学和病理学系录取，接受额外的研究培训，最终获得哲学博士学位。继续进行生物医学研究方面的指导培训，特别强调继续调查TSE的发病机制，对于发展成为独立和合作的研究者是必要的。 环境：该研究项目将创造一个独特的合作机会，利用华盛顿州立大学和华盛顿大学的资源和相关专业知识。华盛顿州立大学将提供与国际公认的教师谁在传染性海绵状脑病的研究专业知识的互动。华盛顿大学和相关的比较医学转基因资源实验室将提供互动与教师和工作人员谁拥有丰富的经验，在转基因技术和使用突变小鼠在现代生物医学研究。这两所大学都建立了教育计划，在生物医学研究方面培养兽医的历史悠久。活动包括每周文献回顾，临床病理会议和研究研讨会。参与这些多渠道的教育和培训机会将为哈灵顿博士提供全面的科学背景，并允许与其研究兴趣领域相关的特定研究培训。

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.