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

与其他哺乳动物和我们现存的近亲--非人类灵长类动物相比，人类的大脑为我们的身体提供了更大的大脑。脑组织需要大量的能量，而人类新陈代谢能量的很大一部分被投入到我们的大脑中。这项研究项目有助于我们理解如何培养和维持我们的大大脑。具体地说，这个项目专注于两种关键类型脑细胞的新陈代谢，并调查它们在人类和非人类灵长类动物中的能量利用途径是如何相似和不同的。该项目使用尖端技术，允许在培养皿中培养不同类型的细胞，而不需要让活动物参与工作。项目调查人员运营着一个由多个大学系组成的工作组，将高级学生聚集在一起共享代码，作为当前项目的一部分，他们领导了一个校园研讨会，旨在向来自服务不足社区的初中和高中女性介绍分析和解释来自基因分析的大数据集的概念。这次研讨会是一项全国性倡议的一部分，该倡议将女孩们带到大学校园，参加一个密集的多年暑期项目。该项目的目标是在细胞水平上研究灵长类动物大脑新陈代谢的进化。研究人员使用尖端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。这项研究的结果被用来检验假设：1)相对于其他灵长类动物，星形胶质细胞在人类和黑猩猩的大脑代谢中表现出明显不同的变化，以及2)人类和黑猩猩正在变化的特定代谢途径不同。星形胶质细胞在大脑环境的多个方面发挥着关键作用，并受到神经退行性疾病的影响。这项研究的结果集中在脑细胞代谢途径的比较上，为理解人脑中发生的代谢过程的戏剧性变化提供了背景，并增强了我们对这些关键的代谢变化如何塑造人脑的理解。这一奖项反映了NSF的法定使命，并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，被认为值得支持。

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.