IMMUNOBIOLOGY OF AGING IN GENETICALLY ALTERED MICE

描述(摘自申请者的摘要)：长期研究 首席调查员(PI)的目标是建立一个国际 公认的利用遗传学研究衰老的免疫生物学项目 更改了小鼠模型。这项建议的具体目的是：1)提供 工资支持和基础设施，使PI大幅增加(50 百分比)在小鼠病理生物学研究中的努力。这将是必要的 从耗时的实验动物药物和管理中解脱 义务，并允许加强对衰老生物学的研究，使用 基因工程小鼠模型；2)研究PKR蛋白的作用 在衰老的生物学中，特别是在免疫系统中， 在转基因小鼠模型中。研究假设是PKR 调控通路是对环境应激的一种广义反应系统， 包括病毒和自由基，是一种保存细胞的尝试 资源。目前有几种小鼠模型可用于进一步研究 如PKR表达与翻译相关T细胞之间的关联 细胞衰老和增殖，增强对流感感染的抵抗力 与衰老相关，以及AGE转录激活的意义- 相关免疫功能障碍和炎症；3)遗传学特征 改变小鼠的衰老模型，特别是在免疫生物学领域， 专注于指导受训者的老鼠病理生物学。一大堆 专门的小鼠表型鉴定专业知识和资源可用于 追求研究目标，为新的研究人员提供培训。这 奖励将使PI从耗时的服务义务中解脱出来， 行政责任，从而增加了 加强衰老生物学方面的研究计划，并指导 下一代老鼠病理生物学家。

DESCRIPTION (Adapted from the applicant's abstract): The long term research goal of the Principal Investigator (PI) is to establish an internationally recognized research program in the immunobiology of aging using genetically altered mouse models. The specific aims of this proposal are: 1) Provide the salary support and infrastructure to allow the PI a significant increase (50 percent) in effort in mouse pathobiology research. This will necessitate being relieved of time consuming laboratory animal medicine and management obligations, and allow enhanced investigation into the biology of aging, using genetically engineered mouse models; 2) Investigate the role of PKR protein kinase pathway genes in the biology of aging, especially of the immune system, in genetically altered mouse models. The research hypothesis is that the PKR regulatory pathway is a generalized response system for environmental stress, including viruses and free radicals, and is an attempt to conserve cellular resources. Several mouse models are currently available to pursue studies such as the association between PKR expression and translation-associated T cell senescence and proliferation, increased resistance to influenza infection associated with aging, and significance of transcriptional activation of age- related immune dysfunction and inflammation; 3) Characterize genetically altered mouse models of aging, especially in the area of immunobiology, with a focus on mentoring trainees in mouse pathobiology. A vast array of specialized mouse phenotyping expertise and resources are available for pursuing the research goals and providing training to new investigators. This award will relieve the PI from time consuming service obligations and administrative responsibilities, thereby increasing the opportunities for enhancing a research program in the biology of aging, and for mentoring the next generation of mouse pathobiologists.