Collaborative Research: URoL: Epigenetics 2: Epigenetics in development and Evolution of Primate Brains

合作研究：URoL：表观遗传学 2：灵长类动物大脑发育和进化中的表观遗传学

• 批准号: 2021785
• 负责人: Chet Sherwood
• 金额: $ 45.88万
• 依托单位: George Washington University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-10-01 至 2024-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2021785&HistoricalAwards=false
• 关键词: Collaborative; Research; URoL; Epigenetics; development; Collaborative; Research; URoL; Epigenetics; development

The proposed research will examine naturally occurring molecular variation in the brains of humans and other primates to understand how modifications to the function of genes in the brain relate to differences in developmental and social experience across species. The proposal is highly interdisciplinary, incorporating methods and perspectives from molecular biology, anthropology, neuroscience and psychology, and will advance fundamental knowledge about mechanistic processes underlying gene-environment interactions in the brains of highly social species. In addition to offering interdisciplinary training for graduate and undergraduate students during the proposed research, the PIs will integrate research opportunities with outreach efforts for high school students, high school teachers, and also for broader public audiences, including children. Comparative studies of primates offer great educational and outreach potential due to their deep implications for understanding humans’ place in nature. Furthermore, the brain is the most widely studied organ in genetic and psychological studies, making the datasets this project will generate especially worthwhile as open resources for the scientific community. All research conducted will be published in peer-reviewed scientific journals and disseminated in scientific meetings. Nonhuman primates have been important model species for the study of mechanisms underlying the biological, genetic and neural basis of a variety of behavioral and cognitive functions. Many aspects of primate brains, including size, structural variation and rate of maturation are tightly associated with life history traits such as cognition, gestation length and life span. These differences are also associated with different developmental rates of primate brains. For example, human brains are extremely immature at birth, followed by slow development, providing ample opportunities for interaction between genome and environment to occur. This research project aims to study the molecular record of such genome-environment interaction in the context of primate brain development. Specifically, the investigators will examine DNA methylation, which functions as cellular memory of environmental input and thus moderates genome-environment interactions, and hypothesize that natural variation in brain size and development of primate species will be reflected in variation of DNA methylation, and in turn, gene expression. Several primate species will be included, encompassing naturally occurring variation in life history traits and brain size. Neocortical areas with distinctive developmental patterns, at cellular resolution, will be compared. In addition to phylogenetic variation, the research will utilize a unique opportunity to investigate how early social experiences have shaped DNA methylation and gene expression within species, using archived samples from chimpanzees and baboon colonies. The proposed research will generate novel opportunities to correlate molecular data with brain and cognitive phenotypes across multiple scales of biology.This project is funded by the Understanding the Rules of Life: Epigenetics Program, administered as part of NSF's Ten Big Ideas through the Division of Emerging Frontiers in the Directorate for Biological Sciences.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

拟议的研究将检查人类和其他主要的大脑中自然存在的分子变异，以了解大脑中基因功能的修改与物种之间发育和社会经验的差异有关。该提案是高度跨学科的，结合了分子生物学，人类学，神经科学和心理学的方法和观点，并将促进有关高度社交物种大脑中基因环境相互作用的机械过程的基本知识。除了在拟议的研究中为研究生和本科生提供跨学科培训外，PI还将研究机会与高中生，高中老师以及包括儿童在内的更广泛的公众受众（包括儿童）的外展工作。私人提供巨大的教育和外展潜力的比较研究，因为它们对人类在自然界中的地位有深远的影响。此外，大脑是遗传和心理学研究中研究最广泛的器官，使该项目成为科学界的开放资源，使数据集成为数据集。所进行的所有研究将发表在经过同行评审的科学期刊上，并在科学会议上传播。非人类灵长类动物一直是研究各种行为和认知功能的生物学，遗传和神经基础的机制的重要模型。灵长类动物大脑的许多方面，包括大小，结构变化和成熟速率与生活历史特征（例如认知，妊娠长度和寿命）紧密相关。这些差异也与灵长类动物大脑的不同发育率有关。例如，人的大脑在出生时就非常不成熟，随后发育缓慢，为基因组和环境之间的相互作用提供了足够的机会。该研究项目旨在研究在初级大脑发育的背景下，这种基因组 - 环境相互作用的分子记录。具体而言，研究人员将检查DNA甲基化，该甲基化作为环境输入的细胞记忆，从而调节基因组 - 环境相互作用，并假设在DNA甲基化的变化中，以及基因表达，将反映在DNA甲基化的变化中，脑大小和灵长类动物物种的自然变异将反映。将包括几种灵长类动物物种，包括生活史特征和大脑大小的自然变化。将比较具有独特发育模式的新皮层区域，在细胞分辨率下将进行比较。除系统发育差异外，该研究还将利用黑猩猩和狒狒菌落的存档样品来研究物种内早期的社会经历如何影响物种内的DNA甲基化和基因表达。拟议的研究将产生新的机会，将分子数据与大脑和认知表型相关联，跨多个生物学范围。该项目由理解生命规则：表观遗传学计划：NSF的十个大思想的一部分，作为通过评估和反映的宣言，是由NSF的十大概念管理的一部分。基金会的智力优点和更广泛的影响评论标准。