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

University Of Massachusetts Amherst, Amherst MA

Investigators

Abstract

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.