Multimodal Delineation of Neurodegenerative Mechanisms

项目摘要 这项提议的目标是培养下一代科学家，以促进我们对人类的理解。 阿尔茨海默病和相关痴呆症（ADRD）在耶鲁大学，并履行发展的承诺， 用于这些使人衰弱的病症的疾病修饰治疗剂。该计划的基本原理是采取 采用综合方法了解ADRD疾病及其合并症的多样性和相似性， 利用细胞生物学、结构生物学、病理学、生物统计学和临床医学。二十九（29）名教师 耶鲁医学院和耶鲁大学的十二（12）个基础和临床部门参与了这项研究。 多学科计划。该计划提供了深度和广度。深度源于专业知识， 研究ADRD的教师和许多可以利用的机构资源，包括， 阿尔茨海默病研究中心（ADRC），帕金森基金会研究中心，三个对齐 最近成立的人类大脑发现中心大脑银行， 以及一座新的研究大楼，大多数导师将在那里办公。该计划的广度源于 从遗传学到药物开发，用于治疗这些疾病的方法多种多样。导师 都是博士和医学博士与大量的NIH支持和NIA/NINDS相关的研究重点。教师调查所有 痴呆的主要形式，包括阿尔茨海默病（AD）、额颞叶痴呆（FTLD）、路易体痴呆（Lewy Body）、 痴呆（LBD）和血管对认知障碍和痴呆的贡献（VCID）。方法 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;电子和先进的光学显微镜;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fMRI和PET成像。六个博士前职位是 所请求学员由执行委员会从优秀的高级人才库中挑选， 神经科学和生物学研究生（第三和第四年），这是在全国最好的， 来自不同的科学背景。学员的选择是基于他们的潜力， 卓越，领导研究以及他们的不同背景。培训包括重点课程， 实验设计和统计方法指导，临床病理相关性（CPC）会议， 通过咨询委员会提供口头和书面反馈，结构化的研讨会计划， 职业技能发展，以及大量的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.