Complex Mouse Models of Age-related Macular Degeneration

描述(由申请人提供)：这份K26中期职业调查员提案的目的是双重的。首先，它将提供在老鼠病理生物学领域支持和指导受训人员的手段。其次，它将为私人助理卡罗琳·蔡司提供手段，以巩固她在视网膜退化领域的研究努力。Caroline Zeiss是一名执业兽医病理学家，在视网膜变性领域进行独立资助的研究(最近通过成功的R21提案)。此外，她还开发并指导了耶鲁大学医学院的小鼠病理表型核心，以及现已全面运作的代谢表型核心。她开发并指导了比较医学部分唯一的研究生课程，最近又开发了一门新的实验动物病理学课程。这些新的资源，加上该科现有的资源，将根据老鼠病理学家联合会最近提出的建议，为制定正式的老鼠病理学培训大纲奠定基础。这一建议的科学基础是建立老年性黄斑变性(AMD)的小鼠模型，并代表了PI既定研究领域的延续。最初提案的第一个目标已经完成。因此，这次重新提交的重点是最近发现的两个与人类AMD相关的基因(CFH和HTRA1)的多态是否能在小鼠中诱发疾病。此外，还纳入了更多的视力研究实验室作为合作者，从而为受训人员提供了获得研究经验的实验室选择。在蔡司博士的指导下，学员将获得老鼠病理学方面的教学和实践经验，并将完成一个旨在出版出版物的有指导的研究项目。经过病理生物学原理培训的比较病理学家的需求已经很明显地存在了好几年。这一需要推动了一些组织的发展，如兽医病理学研究员ACVP/STP联盟。这项建议的支持将为在兽医病理学方面有经验的受训人员提供机会，以获得比较小鼠病理学和表型鉴定以及研究方法方面的广泛经验。 公共卫生相关性(由申请者提供)：K26奖的目的有两个，题为“老年性黄斑变性的复杂小鼠模型”。首先，它将提供在老鼠病理生物学领域支持和指导受训人员的手段。其次，它将为私人助理卡罗琳·蔡司提供手段，以巩固她在视网膜退化领域的研究努力。该奖项为期三年，其成功的资金将支持每年一名学员，并为PI提供受保护的时间来巩固她的实验室并建立坚实的研究支持。

DESCRIPTION (provided by applicant): The intent of this K26 Mid Career Investigator proposal is twofold. First, it will provide the means to support and mentor trainees in the field of mouse pathobiology. Second, it will provide the PI, Caroline Zeiss, with the means to consolidate her research effort in the area of retinal degeneration. Caroline Zeiss is a practicing veterinary pathologist conducting independently funded research (most recently via a successful R21 proposal) in the area of retinal degeneration. In addition, she developed and directs the Mouse Pathologic Phenotyping Core at Yale University School of Medicine as well as its now fully operational Metabolic Phenotyping Core. She developed and directs the Section of Comparative Medicine's only graduate course, and more recently, has developed a new Laboratory Animal Pathology course. These new resources, together with those already available within the Section, will provide the basis for a formal training syllabus in mouse pathobiology in accordance with that recently proposed by the Mouse Pathologist's Consortium. This scientific basis of this proposal is to develop murine models for age-related macular degeneration (AMD), and represents the continuation of the PI's established research field. The first aim of the original proposal has been completed. Therefore this resubmission focuses whether polymorphisms in two recently discovered genes (CFH and HTRA1) that are associated with AMD in humans can induce the disease in mice. Further, additional vision research laboratories have been included as collaborators, thus providing the trainee a choice of laboratories in which to obtain research experience. Under guidance of Dr. Zeiss, trainees will obtain didactic and hands-on experience in mouse pathology, and will complete a mentored research project aimed at generating a publication. The need for comparative pathologists trained in pathobiologic principles has been evident for several years now. This need has provided the impetus for development of organizations such as the ACVP/STP Coalition for Veterinary Pathology Fellows. Support of this proposal would provide opportunities for trainees with experience in veterinary pathology to gain broad experience in comparative mouse pathology and phenotyping as well in research methodology. PUBLIC HEALTH RELEVANCE (provided by applicant): The purpose of this K26 award entitled "Complex mouse models of age-related macular degeneration" is twofold. First, it will provide the means to support and mentor trainees in the field of mouse pathobiology. Second, it will provide the PI, Caroline Zeiss, with the means to consolidate her research effort in the area of retinal degeneration. The award spans three years, and its successful funding will support one trainee per year, and provide protected time for the PI to consolidate her lab and establish solid research support.