Doctoral Dissertation Research: Investigating astrocyte-mediated adaptive changes in primate brain metabolism

人类在饮食和新陈代谢方面的适应很可能与其他重要的人类特征有关，比如我们需要新陈代谢的大大脑。这个博士论文项目将研究星形胶质细胞，这是一种代谢上重要的脑细胞，以确定它们对人脑独特新陈代谢的贡献。这项工作将进一步加深我们对灵长类动物之间进化的新陈代谢和神经差异的理解，同时提供对细胞和遗传水平上未被充分研究但关键的脑细胞类型的洞察。该项目将支持第一代女大学生和研究生的研究，以及主要侧重于揭开基因组的神秘面纱和了解随时可获得的基因组数据的社会影响的公共和K-12科学传播努力的发展。先前的研究一直表明，在几个灵长类物种的大脑中，差异表达的基因的代谢功能丰富。这项提议将研究星形胶质细胞中基因表达和功能的进化，以了解这种细胞类型对人脑独特新陈代谢的贡献程度。研究人员将使用成熟的、非侵入性的细胞培养方法，从人类和黑猩猩的诱导多能干细胞中培养和发育星形胶质细胞。这些星形胶质细胞将被检测基因表达的差异和代谢功能的重要特征，例如细胞中的葡萄糖摄取。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Human adaptations in diet and metabolism are likely to be linked to other important human traits, like our large, metabolically demanding brains. This doctoral dissertation project will study astrocytes, a type of metabolically important brain cell, to determine their contribution to the unique metabolism of the human brain. This work will further our understanding of evolved metabolic and neurological differences among primates, while providing insight into an understudied, but critical cell type of the brain at the cellular and genetic levels. This project will support the research of a first-generation female college and graduate student, as well as the development of public and K-12 science communication efforts largely focused on demystifying the genome and understanding the societal implications of readily accessible genomic data. Previous research has consistently shown enrichment of metabolic function in genes differentially expressed between the brains of several primate species. This proposal will investigate the evolution of gene expression and function in astrocytes, to understand the extent to which this cell type contributes to the unique metabolism of the human brain. The investigators will use established, non-invasive cell culture methods to grow and develop astrocytes from induced pluripotent stem cells of both humans and chimpanzees. These astrocytes will be assayed for differences in gene expression and traits important for metabolic function, such as glucose uptake into the cell.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.