IMMUNOBIOLOGY OF AGING IN GENETICALLY ALTERED MICE

描述（改编自申请人摘要）：长期研究 主要研究者（PI）的目标是建立一个国际性的 公认的研究计划，在免疫生物学的老化，利用遗传 改变小鼠模型。 该提案的具体目标是：1）提供 工资支持和基础设施，使PI显着增加（50 %），用于小鼠病理学研究。 这将需要 从耗时的实验动物医学和管理中解脱出来 义务，并允许加强对衰老生物学的调查，使用 2）研究PKR蛋白的作用 激酶途径基因在衰老生物学中，特别是在免疫系统中， 在转基因小鼠模型中。 研究假设PKR 调节途径是一种广义的环境应激反应系统， 包括病毒和自由基，并试图保护细胞 资源 目前有几种小鼠模型可用于研究 例如PKR表达与肿瘤相关T细胞之间的关系， 细胞衰老和增殖，增强对流感感染的抵抗力 与衰老相关，以及年龄的转录激活的重要性- 相关的免疫功能障碍和炎症; 3）表征遗传学 改变衰老的小鼠模型，特别是在免疫生物学领域， 专注于指导小鼠病理学的学员。 和更便利的 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，并为新的研究人员提供培训。 这 奖励将免除PI耗时的服务义务， 行政责任，从而增加了机会， 加强衰老生物学的研究计划，并指导 下一代小鼠病理学家

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.