Mentoring and Research in Mouse Pathobiology

描述(申请人提供)：随着基因工程小鼠模型的爆炸性增长，小鼠病理生物学家在生物医学研究中有巨大的机会。首席调查员的职业目标是成为一名更加独立和成功的小鼠病理生物学研究人员，并利用现有的技能以及通过这项提议发展出来的技能来指导下一代小鼠病理生物学专家。他作为一名科学家的成长一直受到与服务、行政和教学职责相关的时间限制的阻碍。这一奖项将使他从其中一些责任中解脱出来，并将时间重新分配给其他人，以便他将有更集中和密集的研究时间。凭借他在训练和病理学方面的广泛背景，他在独立和合作研究方面的经验，以及他促进和促进小鼠病理生物学研究和培训的环境，候选人非常有资格获得这一奖项。这一环境包括一个比较医学培训计划、一个世界著名的研究动物诊断实验室、一个比较医学研究中心和四个突变小鼠区域资源中心之一。长期的研究目标包括揭开慢性肠炎性疾病的机制，从而最终能够开发出新的预防和治疗策略。这项提案的目标集中在男性和女性在肠道粘膜炎症性疾病方面的差异。为了实现这些目标，将采用以下特定的目标：1)确定A/J小鼠由肝炎杆菌引起的粘膜炎症的细胞类型；2)评估性腺类固醇激素、雌激素和睾酮在细菌引发的粘膜炎症发病机制中的作用；3)评估通过雌激素受体α(ERe0)和β(ERL3)的免疫细胞的雌激素信号在粘膜炎症中的作用。这些项目将为老鼠病理生物学方面的个人培训提供一个理想的论坛，并使他们能够开始从事研究并成为该领域的领导者。

DESCRIPTION (provided by applicant): With the explosion of genetically engineered mouse models, there are enormous opportunities for mouse pathobiologists in biomedical research. The Principal Investigator's career objectives are to become a more independent and successful mouse pathobiology researcher and to use existing skills as well as those developed through this proposal to mentor the next generation of mouse pathobiologists. His growth as a scientist has been hindered by time constraints associated with service, administrative and teaching responsibilities. This award will provide release from some of these responsibilities and redistribution of time in others so that he will have more focused and intensive research time. The candidate is very well qualified for this award by virtue of his extensive background in training and pathology, his experience in both independent and collaborative research and his environment which facilitates and promotes mouse pathobiology research and training. This environment includes a Comparative Medicine Training Program, a world-renowned Research Animal Diagnostic Laboratory, a Comparative Medicine Research Center and one of four Mutant Mouse Regional Resource Centers. Long-term research goals include unraveling the mechanisms of chronic intestinal inflammatory disease so that ultimately novel prevention and treatment strategies can be developed. The objectives of this proposal focus on differences seen between males and females in inflammatory diseases of the intestinal mucosa. The following specific aims will be employed in pursuit of these objectives: 1) determine what cell types characterize mucosal inflammation caused by H. hepaticus in the A/J mouse 2) assess the role of the gonadal steroid hormones, estrogen and testosterone, in pathogenesis of bacterial initiated mucosal inflammation and 3) assess the role of estrogen signaling of immune cells via estrogen receptor alpha (ERe0 and beta (ERL3) in mucosal inflammation. These projects will provide an ideal forum for the training of individuals in mouse pathobiology and enable them to initiate careers in research and become leaders in this field.