The genomics of metabolic change in human and non-human primate brain evolution

人类和非人类灵长类动物大脑进化代谢变化的基因组学

• 批准号: 2146668
• 负责人: Courtney Babbitt
• 金额: $ 47.33万
• 依托单位: University of Massachusetts Amherst
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2146668&HistoricalAwards=false
• 关键词: genomics; metabolic; change; human; non

Humans have large brains for our bodies compared to other mammals and to our closest living relatives, the nonhuman primates. Brain tissue requires a lot of energy, and a good portion of human metabolic energy is devoted to our brains. This research project contributes to our understanding of how we can afford to grow and maintain our large brains. Specifically, this project focuses on the metabolism of two key types of brain cells and investigates how their pathways for energy use are similar and different between humans and nonhuman primates. This project uses cutting-edge techniques that allow the growing of cell types in a dish, without involving living animals in the work. The project investigators run a working group of multiple university departments that bring together advanced students to share code, and as part of the current project lead an on-campus workshop aimed at introducing middle and high school women from underserved communities to concepts in analyzing and interpreting large datasets from genetic analysis. This workshop is part of a national initiative that brings girls onto college and university campuses for an intensive multi-year summer program. The objective of this project is to examine the evolution of metabolism in the primate brain at the cellular level. Investigators use cutting edge methods to transform cells from humans and nonhuman primates into neurons and astrocytes. The results of this study are used to test hypotheses that 1) relative to other primates, astrocytes show significantly different changes in brain metabolism in humans and chimpanzees, and 2) the specific metabolic pathways that are changing in humans and chimpanzees are not the same. Astrocytes play key roles in multiple aspects of the brain’s environment and are modified by neurodegenerative disease. The results of this research, focused on comparisons of brain cell metabolic pathways, provides context for understanding dramatic shifts in metabolic processes that have occurred in the human brain, and enhance our understanding of how these critical metabolic changes have shaped the human brain.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.

与其他哺乳动物和我们的近亲——非人灵长类动物相比，人类的大脑更大。大脑组织需要大量的能量，而人体代谢能量的很大一部分都用于我们的大脑。这个研究项目有助于我们理解我们如何能够负担得起发展和维持我们的大大脑。具体来说，该项目侧重于两种关键类型脑细胞的代谢，并研究它们的能量使用途径在人类和非人类灵长类动物之间是如何相似和不同的。该项目采用了尖端技术，可以在培养皿中培养不同类型的细胞，而不涉及活体动物。项目调查人员管理着一个由多个大学院系组成的工作组，将高级学生聚集在一起共享代码，并作为当前项目的一部分，领导一个校园研讨会，旨在向来自服务不足社区的初高中女性介绍分析和解释基因分析大数据集的概念。这个研讨会是一项全国倡议的一部分，该倡议将女孩带到学院和大学校园，参加为期数年的密集暑期课程。该项目的目的是在细胞水平上研究灵长类动物大脑代谢的进化。研究人员使用尖端的方法将人类和非人类灵长类动物的细胞转化为神经元和星形胶质细胞。本研究的结果用于验证以下假设：1)相对于其他灵长类动物，人类和黑猩猩的星形胶质细胞在脑代谢方面表现出明显不同的变化；2)人类和黑猩猩的特定代谢途径的变化并不相同。星形胶质细胞在大脑环境的多个方面发挥关键作用，并被神经退行性疾病所改变。这项研究的结果侧重于脑细胞代谢途径的比较，为理解人类大脑中发生的代谢过程的急剧变化提供了背景，并增强了我们对这些关键代谢变化如何塑造人类大脑的理解。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。