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

与其他哺乳动物和我们最近的近亲非人类灵长类动物相比，人类的身体有更大的大脑。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增长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的脑细胞的代谢，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的相似性和不同性。该项目使用尖端技术，允许在培养皿中生长细胞类型，而不涉及活动物。该项目的研究人员运行多个大学部门的工作组，汇集先进的学生共享代码，并作为当前项目的一部分，导致一个校园研讨会，旨在介绍初中和高中妇女从服务不足的社区的概念，在分析和解释遗传分析的大型数据集。该讲习班是一项国家倡议的一部分，该倡议将女孩带到学院和大学校园，参加一个密集的多年暑期课程。本项目的目的是在细胞水平上研究灵长类动物大脑中代谢的进化。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。 本研究的结果用于检验以下假设：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显示出显著不同的变化，2）人类和黑猩猩正在变化的特定代谢途径并不相同。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改变。这项研究的结果集中在脑细胞代谢途径的比较上，为理解人类大脑中发生的代谢过程的巨大变化提供了背景，该奖项反映了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进行评估，被认为值得支持审查标准。

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.