Training in the Molecular Basis of Autoimmunity and Autoinflammation

摘要 在过去的15年里，我们对潜在的复杂机制的理解发生了范式转变 自身免疫性疾病，对先天免疫和获得性免疫之间的相互作用有更深入的了解 系统组件，导致先天和获得性免疫介导的组织破坏的机制， 动物模型与人类疾病的相关性，以及产生功能移植所需的因素 组织。利用所有这些洞察力并开发阻止自身反应的新治疗策略 应对，并允许修复和/或替换受损的器官，将需要下一代 对基础免疫学、细胞生物学、分子生物学、系统生物学有广泛了解的科学家 和信息学。拟议的关于自身免疫和自体炎症的分子基础的培训将培训 通过聚集高技能和协作导师，在这些重要领域进行博士前研究 来自多个学科，最终目标是为这些衰弱的疾病开发新的治疗方法。我们 也了解到一系列易感基因在自身免疫性疾病中共享，这表明 共同的道路。更好地了解这些易感基因是如何促进耐受性丧失和 高反应性也将是有效治疗自身免疫性疾病的关键。培训调查人员以满足 这些科学研究的挑战，我们的培训环境必须包含跨学科的主题和 提供这一领域最先进的研究机会，并提供其他方面的培训 职业发展。因此，该计划的具体目标将是：(1)提供有才华的博士 具有概念和技术技能的候选人，能够处理以下领域中有意义的、与临床相关的主题 自身免疫；(2)促进学员和培训人员之间的沟通和协作互动； (3)为将研究成果转化为临床提供机会；。(4)建立机制，以 招募更多人数不足的少数族裔担任该机构的博士后职位；(5) 为学员提供较强的口头陈述、手稿写作、助学金写作、人际网络等基本技能 职业发展技能；以及(6)为受训人员提供参与地方、国家和 他们可以在国际会议上分享自己的研究成果。该计划是高度交叉的- 纪律，纳入18名有经验的调查人员作为导师，他们代表了广泛的 正在应用于自身免疫/自身炎症研究的研究专业知识和技术 条件。培训人员包括从事基础和翻译工作的MD和MD-PhD科学家， 以疾病为导向的研究教职员工已经参与了高效率的协作，并拥有 丰富的博士前培训经验。项目联合主任将通过两次培训获得建议 教职员工和由杰出科学家/培训基金主任组成的外部咨询委员会 对自身免疫和自体炎症感兴趣。重要的是，项目负责人将与 密歇根州立大学职业发展办公室提供关键职业技能培训，使学员能够 将他们的研究成果带到成功的学术生涯中。

ABSTRACT The past 15 years has seen a paradigm shift in our understanding of the complex mechanisms underlying autoimmune diseases with a greater understanding of the interplay between innate and adaptive immune system components, the mechanisms that lead to innate and adaptive immune mediated tissue destruction, the relevance of animal models to human disease, and the factors needed to generate functional transplant tissue. To capitalize on all of these insights and develop novel therapeutic strategies that block autoreactive responses and also permit the repair and/or replacement of damaged organs, will require a next generation of scientists with a broad understanding of basic immunology, cell biology, molecular biology, systems biology and informatics. The proposed Training in the Molecular Basis of Autoimmunity and Autoinflammation will train predoctoral investigators in these important areas by bringing together highly skilled and collaborative mentors from multiple disciplines, with the ultimate goal of developing new therapies for these debilitating diseases. We have also learned that an array of susceptibility genes are shared among autoimmune diseases, indicative of common pathways. A better understanding of how these susceptibility genes promote the loss of tolerance and hyperreactivity will also be key to effective treatments for autoimmune diseases. To train investigators to meet these challenges of scientific inquiry, our training environments must embrace cross-disciplinary themes and provide both state-of-the-art research opportunities in this area, and also provide training in other aspects of career development. Therefore, the specific goals of this program will be to: (1) provide talented PhD candidates with conceptual and technological skills to tackle meaningful, clinically relevant topics in the area of autoimmunity; (2) facilitate communication and collaborative interactions amongst trainees and training faculty; (3) provide opportunities for the translation of research discoveries to the clinics; (4) establish mechanisms for recruiting increased numbers underrepresented minorities to postdoctoral positions at this institution; (5) provide trainees with strong oral presentation, manuscript writing, grant writing, networking, and other essential career development skills; and (6) provide trainees with opportunities to participate in local, national, and international meetings where they can share their own research findings. The program is highly cross- disciplinary, incorporating 18 accomplished investigators as mentors who represent a broad spectrum of research expertise and technologies that are being applied to the study of autoimmune/autoinflammatory conditions. The training faculty includes MD and MD-PhD scientists engaged in basic and translational, disease-oriented research. Faculty members are already involved in highly productive collaborations and have extensive experience in predoctoral training. The program co-directors will be advised by both the training faculty and an External Advisory Committee comprised of distinguished scientists/training grant directors with interests in autoimmunity and autoinflammation. Importantly, the program directors will work closely with the UMMS Office of Career Development to provide training in critical career skills that will further enable trainees to carry their research accomplishments forward to successful academic careers.