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

项目摘要 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，Aβ聚集的AD标志与睡眠的变化有关- 唤醒模式和昼夜节律相关的新陈代谢。由于这些变化发生在临床表现之前数年 可能是AD的早期事件。为了理解这种关系，睡眠/昼夜节律生物学和 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志物研究 如小鼠，并且研究集中在基因组技术的最新进展（例如，单细胞 RNA-seq和表观基因组学），允许更精确地描述发生的分子和细胞变化， 年龄、睡眠/昼夜节律和AD进展的函数。由于这些领域的研究尚处于起步阶段， 交叉的关键阶段，我们认识到睡眠/昼夜节律生物学研究人员需要了解 从他们在AD的同事那里，反之亦然。目前，在老龄化/AD领域没有会议纳入 睡眠/昼夜节律生物学，更不用说专注于遗传学，基因组学和计算生物学方法。填补 这一差距，我们建议独特和及时的跨学科会议“睡眠和昼夜节律生物学的影响 关于阿尔茨海默病和衰老：关注遗传学和基因组学”，以激发 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， 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开始。我们将 汇集了50名科学家-研究生，博士后研究员，初级和高级研究人员-从 衰老/AD、神经变性、睡眠遗传学/昼夜节律生物学、遗传学和计算 生物学在目标1中，我们将组织这次关于睡眠/昼夜节律生物学和AD的跨学科会议， 专注于遗传学和基因组学方法。特邀演讲者和会议主题将代表各种 旨在解决AD相关问题的学科。每天上午的研讨会将介绍学员在 AD领域的睡眠/昼夜节律生物学的基础知识和先进的计算方法在遗传学和 基因组学，而下午的动手工作坊将侧重于“组学”分析，以刺激学员自己的研究。 在目标2中，我们将促进促进合作研究和职业发展的互动。我们将包括 休息和海报会议作为自由形式讨论的机会，以及专门一个工作坊的职业生涯 发展，包括粮食安全和道德。为了促进包容性和创造性的科学，在目标3中，我们将重点关注 招募不同的与会者，利用我们的伙伴关系协会和网络招募代表性不足的人 少数民族和弱势群体的与会者，以及提供奖学金给那些谁资格和需要。我们 我预计，会议和研讨会将交叉授粉领域的睡眠/昼夜节律生物学和AD 在为下一代AD和睡眠/昼夜节律生物学研究人员提供装备的同时， 在他们的研究中利用先进的计算方法的能力。

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.