Doctoral Dissertation Research: Genetic Changes During Human Brain Evolution

博士论文研究：人脑进化过程中的基因变化

• 批准号: 1919671
• 负责人: Stephanie Bielas
• 金额: $ 3.1万
• 依托单位: Regents of the University of Michigan - Ann Arbor
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2022-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1919671&HistoricalAwards=false
• 关键词: Doctoral; Dissertation; Research; Genetic; Changes

Humans evolved very large brains relative to their body size, with a remarkable enrichment of neurons in the cerebral cortex. Extensive efforts in anthropology have focused on delineating the adaptive pressures that led to these changes during human evolution. However, the genetic changes underlying human brain expansion have not been fully explored. This project will test hypotheses about human brain evolution by studying the impact of human genetic variation on brain development using experimental models. This research has broad implications for understanding what makes the human brain unique at the cellular and molecular levels, with translational value for medical treatment of neurodevelopmental disorders. During this research, undergraduate students pursuing careers in STEM will be mentored and trained in molecular biology and bioinformatics techniques in the laboratory. Research findings will be used as 1) an educational tool for spreading knowledge about human evolution and genetics with the general public, K-12 students, and undergraduate students, as well as 2) a motivational platform for the young, future women scientists in the Females Excelling More in Mathematics, Engineering and Science (FEMMES) Program. The proposed research takes a multi-disciplinary approach to investigate how human evolutionary history has shaped the molecular and physiological mechanisms of human brain expansion. In the laboratory, human and non-human primate neural cells will be studied to explore how genetic variation evolved in humans to shape the developing brain. This project uses a combination of gene editing, RNA sequencing, and immunohistochemistry to determine the functional role of human-specific genetic sequence during brain development that corresponds to changes in brain size. These findings will advance the understanding of the molecular evolution of 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.

相对于他们的身体大小，人类进化出了非常大的大脑，大脑皮层中的神经元显著丰富。人类学的广泛努力集中在描绘在人类进化过程中导致这些变化的适应压力。然而，人类大脑扩张背后的基因变化还没有得到充分的探索。这个项目将通过使用实验模型研究人类基因变异对大脑发育的影响来检验关于人类大脑进化的假说。这项研究对于理解人类大脑在细胞和分子水平上的独特之处具有广泛的意义，对神经发育障碍的医疗具有翻译价值。在这项研究期间，在STEM寻求职业生涯的本科生将在实验室接受分子生物学和生物信息学技术的指导和培训。研究成果将被用作1)向普通公众、K-12学生和本科生传播人类进化和遗传学知识的教育工具，以及2)为女性中在数学、工程和科学(FETMES)项目中表现更出色的年轻、未来的女科学家提供激励平台。这项拟议的研究采用了多学科的方法来研究人类进化史是如何塑造人类大脑扩张的分子和生理机制的。在实验室中，将研究人类和非人类灵长类神经细胞，以探索人类的遗传变异如何演变为塑造发育中的大脑。该项目使用基因编辑、RNA测序和免疫组织化学相结合的方法来确定人类特有的基因序列在大脑发育过程中的功能作用，这与大脑大小的变化相对应。这些发现将促进对人脑分子进化的理解。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。