Transmission of Prions Within and Between Species

描述(申请人提供)：研究建议：传播性海绵状脑病(TSE)是一组慢性的、总是致命的神经退行性疾病。慢性消耗性疾病(CWD)是野生和圈养麋鹿、骡鹿和白尾鹿中的一种TSE。口腔传播在许多TSE中都有记录，并在给出CWD传染病材料的鹿身上进行了实验复制。CWD对其他物种的口服传播性仍不确定。CWD的潜在宿主包括食用鹿肉的人类、野生食肉动物和在农业上具有重要意义的反刍动物。在一些物种中已经发现了影响TSE易感性的遗传多态，并可能影响CWD的传播。我将在转基因模型中测试CWD的口腔传染性，以确定氨基酸多态对疾病易感性的影响。我将测试自然TSE宿主的口腔传染性，以进一步确定TSE在物种之间的宿主范围。由于CWD阳性动物的地理传播，以及有证据表明牛海绵状脑病(影响牛的TSE)具有人畜共患潜力，此类研究是及时的和具有时效性的。 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方面的实习。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，对于发展成为一个独立和合作的研究人员是必要的。 环境：该研究项目将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创造一个独特的合作机会。华盛顿州立大学将与在传染性海绵状脑病研究方面拥有专业知识的国际公认的教师进行互动。华盛顿大学和相关的比较医学转基因资源实验室将与在转基因技术和在现代生物医学研究中使用突变小鼠方面拥有丰富经验的教职员工进行互动。这两所大学都建立了教育项目，在生物医学研究方面培训兽医方面有着卓有成效的历史。活动包括每周文献回顾、临床病理学会议和研究研讨会。参与这多种来源的教育和培训机会将为哈林顿博士提供全面的科学背景，并允许进行与他的研究兴趣领域相关的具体研究培训。

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.