Multimodal Delineation of Neurodegenerative Mechanisms

项目总结 这项提议的目标是培养下一代科学家，这将促进我们对 耶鲁大学的阿尔茨海默病和相关痴呆症(ADRD)，并实现发展的承诺 针对这些衰弱状况的疾病修正疗法。这个计划的基本原理是采取一种 以综合方法了解ADRD疾病的多样性和相似性及其共同发病情况， 运用细胞生物学、结构生物学、病理学、生物统计学和临床医学。二十九(29)名来自 耶鲁医学院和耶鲁学院的十二(12)个基础系和临床系参与了这项活动 多学科项目。该项目既有深度，也有广度。深度来自于 调查ADRDS的教职员工和可以利用的许多机构资源，包括 阿尔茨海默病研究中心(ADRC)，帕金森基金会研究中心，三个联合 帕金森团队的科学(ASAP)，一个最近成立的人脑发现中心脑库， 以及一座新的研究大楼，大多数导师将在这里共同办公。程序的广度来自于 解决这些疾病的方法多种多样，从遗传学到药物开发都有。导师 都是博士。还有医学博士。有大量的NIH支持和NIA/NINDS相关研究重点。教职员工调查所有 痴呆症的主要形式，包括阿尔茨海默病(AD)、额颞痴呆(FTLD)、路易体 痴呆症(LBD)和血管对认知损害和痴呆的贡献(VCID)。方法论 包括深度测序；转录组学；蛋白质组学；细胞和诱导多能干细胞(IPSC)培养； 免疫组织化学；电子显微镜和高级光学显微镜；生物化学和分子分析；结构 生物学；啮齿动物、猴子行为；以及人类受试者的功能磁共振成像和正电子发射计算机断层成像。六个博士前职位是 已请求。实习生由执行委员会从优秀的高级人才库中挑选出来 神经科学和生物学研究生(3年级和4年级)，在全国名列前茅， 来自不同的科学背景。实习生是根据他们在以下方面的潜力来挑选的 优秀、在研究方面的领导地位以及他们不同的背景。培训包括有重点的课程工作， 指导实验设计和统计方法，临床病理相关(CPC)会议， 通过咨询委员会提供深思熟虑的指导，提供口头和书面反馈，组织研讨会计划， 职业技能发展，以及大量书面和口头介绍研究进展的机会。

PROJECT SUMMARY The goal of this proposal is to train the next generation of scientists that will advance our understanding of Alzheimer’s Disease and Related Dementias (ADRD) at Yale University, and to fulfil the promise of developing disease-modifying therapeutics for these debilitating conditions. The rationale of this program is to take an integrated approach to understand the diversity and similarities of ADRD conditions as well as their co-morbidity, using cell biology, structural biology, pathology, biostatistics, and clinical medicine. Twenty nine (29) faculty from twelve (12) basic and clinical departments at Yale School of Medicine and Yale College are participants in this multidisciplinary program. The program offers both depth and breadth. The depth derives from the expertise of the faculty investigating ADRDs and the many institutional resources that can be brought to bear including, an Alzheimer’s Disease Research Center (ADRC), a Parkinson’s Foundation Research Center, three Aligning Science Across Parkinson’s (ASAP) teams, a recently instituted Center for Human Brain Discovery brain bank, and a new research building where most mentors will co-locate. The breadth of the program derives from the diversity of approaches being used to tackle these diseases ranging from genetics to drug development. Mentors are Ph.Ds. and M.D.s. with substantial NIH support and NIA/NINDS related research foci. Faculty investigate all major forms of dementia, including Alzheimer’s disease (AD), Frontotemporal Dementia (FTLD), Lewy Body Dementia (LBD), and Vascular contributions to cognitive impairment and dementia (VCID). Methodologies include deep sequencing; transcriptomics; proteomics; cell and induced pluripotent stem cell (iPSC) culture; immunohistochemistry; electron and advanced light microscopy; biochemistry and molecular analyses; structural biology; rodent, monkey behavior; and fMRI and PET imaging in human subjects. Six predoctoral positions are requested. Trainees are selected by the Executive Committee from an outstanding pool of advanced Neuroscience and Biology graduate students (3rd and 4th year), which are amongst the best in the country and come from a variety of backgrounds in the sciences. Trainees are selected based on their potential for excellence, leadership in research as well as their diverse backgrounds. Training includes focused coursework, instruction in experimental design and statistical methods, Clinicopathologic correlation (CPC) conferences, thoughtful mentorship through advisory committees with oral and written feedback, structured seminar programs, career skills development, and numerous opportunities for written and oral presentation of research progress.