Impacts of Sleep and Circadian Biology on Alzheimer's Disease and Aging: A Focus on Genetics and Genomics

项目总结 一个新兴的研究领域是衰老、睡眠和昼夜节律与阿尔茨海默氏症之间的关系 疾病(AD)进展。例如，β聚合的AD标志与睡眠变化相关- 觉醒模式和昼夜节律相关的新陈代谢。因为这些变化发生在临床表现的前几年 在AD中，它们可能是AD的早期事件。为了理解这种关系，睡眠/昼夜生物学和 AD正在采取类似的策略，包括在人类和模式生物中进行遗传和生物标记物研究 例如小鼠，研究集中在基因组技术的最新进展上(例如，单细胞 RNA-SEQ和表观基因组学)，允许更精确地描述发生在 年龄、睡眠/昼夜节律和AD进展的函数。由于这些领域的研究还处于初级阶段， 在交叉点的关键阶段，我们认识到睡眠/昼夜生物学研究人员需要学习的未得到满足的需求 来自他们在AD的同事，反之亦然。目前，没有老龄/AD领域的会议纳入 睡眠/昼夜生物学，更不用说关注遗传学、基因组学和计算生物学方法了。填满 在这一空白中，我们提出了独特而及时的跨学科会议《睡眠与昼夜生物学的影响》 关于阿尔茨海默病和衰老：遗传学和基因组学的焦点“点燃有焦点的 来自这些领域的科学家和受训人员组成的小组，并促进未来的合作。我们建议每年举办一次， 为期3天的密集会议将于2021年10月在缅因州巴尔港的杰克逊实验室举行。我们会 汇集50名科学家--研究生、博士后研究员、初级和高级研究人员--来自 衰老/阿尔茨海默病、神经变性、睡眠遗传学/昼夜生物学、遗传学和计算领域 生物学。在目标1中，我们将组织这次关于睡眠/昼夜生物学和阿尔茨海默病的跨学科会议 重点关注遗传和基因组方法。特邀演讲者和会议主题将代表各种 旨在解决与AD相关的问题的学科。每天的早间研讨会将向学员介绍 睡眠/昼夜生物学的基本原理以及遗传学和生物学的高级计算方法的AD领域 基因组学，而下午的实践研讨会将重点放在“组学”分析上，以推动学员自己的研究。 在目标2中，我们将促进互动，促进合作研究和职业发展。我们将包括 休息时间和海报会议，作为自由形式讨论的机会，以及致力于职业生涯的研讨会 发展，包括赠款精神和道德规范。为了促进包容性和创造性的科学，在目标3中，我们将重点 关于招募不同的与会者，利用我们的伙伴关系协会和网络来招聘代表性不足的人员 向少数群体和弱势参与者提供奖学金，并向符合条件和有需要的人提供奖学金。我们 预计会议和研讨会将交叉授粉睡眠/昼夜生物学和阿尔茨海默病 并在装备下一代AD和睡眠/昼夜生物学研究人员的同时，为新的合作奠定基础 能够在他们的研究中利用先进的计算方法。

PROJECT SUMMARY An emerging area of investigation is the relationship between aging, sleep and circadian rhythm, and Alzheimer’s disease (AD) progression. For example, the AD hallmark of Aβ aggregation is associated with changes in sleep- wake patterns and circadian-related metabolism. As these changes occur years prior to clinical manifestations of AD, they may be early events in AD. To understand this relationship, the fields of sleep/circadian biology and AD are taking similar strategies that include genetic and biomarker studies in humans and model organisms such as the mouse, and research is converging on recent advances in genomic technologies (e.g., single-cell RNA-seq and epigenomics) that allow more precise description of molecular and cellular changes that occur as a function of age, sleep/circadian rhythm, and AD progression. As studies in these fields are at the nascent and critical stage of intersection, we recognize an unmet need for investigators in sleep/circadian biology to learn from their colleagues in AD, and vice versa. Currently, no conference in the aging/AD field incorporates sleep/circadian biology, let alone focuses on genetics, genomics, and computational biology approaches. To fill this gap, we propose the unique and timely interdisciplinary conference “Impacts of Sleep and Circadian Biology on Alzheimer’s Disease and Aging: a Focus on Genetics and Genomics” to ignite interactions among a focused group of scientists and trainees from these fields and to foster future collaborations. We propose an annual, intensive 3-day conference beginning in October, 2021 at The Jackson Laboratory in Bar Harbor, ME. We will bring together 50 scientists -- graduate students, postdoctoral fellows, and junior and senior investigators -- from the fields of aging/AD, neurodegeneration, genetics of sleep/circadian biology, genetics, and computational biology. In Aim 1, we will organize this interdisciplinary conference on sleep/circadian biology and AD with a focus on genetic and genomic approaches. Invited speakers and session topics will represent a variety of disciplines that aim to solve questions related to AD. Each day a morning seminar will introduce trainees in the AD field to the fundamentals of sleep/circadian biology and advanced computational approaches in genetics and genomics while a hands-on afternoon workshop will focus on 'omics' analyses to spur the trainees' own research. In Aim 2, we will promote interactions that foster collaborative research and career advancement. We will include breaks and a poster session as opportunities for free-form discussions as well as devote one workshop to career development, including grantsmanship and ethics. To foster inclusive and creative science, in Aim 3 we will focus on recruitment of diverse attendees, utilizing our partnership societies and networks to recruit underrepresented minority and disadvantaged attendees, as well as offering scholarships to those who qualify and are in need. We anticipate that the conference and workshops will cross-pollinate the fields of sleep/circadian biology and AD and seed new collaborations while equipping the next generation of AD and sleep/circadian biology researchers with the ability to harness advanced computational approaches in their research.