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: 2204761
• 负责人: Soojin Yi
• 金额: $ 168.92万
• 依托单位: University of California-Santa Barbara
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-10-01 至 2024-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2204761&HistoricalAwards=false
• 关键词: 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灵长类动物大脑中自然发生的分子变异，以了解大脑中基因功能的改变如何与跨物种的发育和社会经历的差异相关。该提案是高度跨学科的，融合了方法和观点。来自分子生物学、人类学、神经科学和心理学的研究人员，将推进有关高度社会化物种大脑中基因与环境相互作用的机制过程的基础知识。 除了在拟议的研究期间为研究生和本科生提供跨学科培训外，PI还将推进这一过程。将研究机会与推广工作结合起来对于高中生、高中教师以及包括儿童在内的更广泛的公众来说，灵长类动物的比较研究因其对理解人类在自然界中的地位的深刻影响而具有巨大的教育和推广潜力。此外，大脑是最广泛的。遗传和心理学研究中的器官，使得该项目将产生的数据集作为科学界的开放资源特别有价值，所有研究都将在同行评审的科学期刊上发表并在科学会议上传播。用于研究其背后的机制灵长类动物大脑的许多方面，包括大小、结构变异和成熟速度，与认知、妊娠长度和寿命等生活史特征密切相关。也与灵长类大脑的不同发育速度有关，例如，人类大脑在出生时极其不成熟，随后发育缓慢，为基因组与环境之间发生相互作用提供了充足的机会，该研究项目旨在研究此类基因组的分子记录。 - 上下文中的环境交互具体来说，研究人员将检查 DNA 甲基化，它作为环境输入的细胞记忆，从而调节基因组与环境的相互作用，并发现大脑大小和灵长类动物发育的自然变化将反映在 DNA 的变化中。除了系统发育变异之外，还将包括几种灵长类动物物种，包括生命史特征和大脑大小的自然变化，以及细胞分辨率上的独特发育模式。研究将利用利用黑猩猩和狒狒群体的存档样本，研究早期社会经历如何影响物种内的 DNA 甲基化和基因表达。这项拟议的研究将产生新的机会，将分子数据与多个生物学尺度的大脑和认知表型联系起来。该项目由理解生命规则：表观遗传学计划资助，该计划作为 NSF 十大理念的一部分，通过生物科学理事会新兴前沿部门进行管理。该奖项反映了 NSF 的法定使命和通过使用基金会的智力价值和更广泛的影响审查标准进行评估，该项目被认为值得支持。

项目成果

Molecular features driving cellular complexity of human brain evolution

驱动人脑进化细胞复杂性的分子特征

• DOI: 10.1038/s41586-023-06338-4
• 发表时间: 2023-08
• 期刊: Nature
• 影响因子: 64.8
• 作者: Caglayan, Emre;Ayhan, Fatma;Liu, Yuxiang;Vollmer, Rachael M.;Oh, Emily;Sherwood, Chet C.;Preuss, Todd M.;Yi, Soojin V.;Konopka, Genevieve
• 通讯作者: Konopka, Genevieve