NSF2026: EAGER: The evolution and diversity of the human brain

NSF2026：EAGER：人脑的进化和多样性

• 批准号: 2034037
• 负责人: Richard Green
• 金额: $ 30万
• 依托单位: University of California-Santa Cruz
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-10-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2034037&HistoricalAwards=false
• 关键词: NSF2026; EAGER; evolution; diversity; human

Human-specific cognitive capacity is evident in many forms. For example, no other species rivals humans’ capacity for speech and language or inter-generational accumulation of knowledge. But what are the genetic underpinnings of human-specific brain evolution and cognition? This project will contrast the genomes of our closest extinct relatives (Neanderthals and Denisovans) with human genomes to identify genetic variants that may play a role in the evolution of human-specific brain. Genomic methods will be used to insert the archaic versions of these genes into human-derived cells. The biology of cells that carry genetic variants that have been extinct for thousands of years will then be studied to help discover recently evolved functions in human brain development and cognition. This project will provide graduate training opportunities in computational genome analysis and experimental genome manipulation. The results of this project have high potential for general public interest as they address fundamental aspects of human uniqueness, and the project may generate opportunities for wide dissemination via public media channels. Further, this project may inform clinical and biomedical research by experimentally describing the functions of genes that work in early brain development. The proposed research enriches the NSF2026 Idea Machine winning entries of 'Harnessing the Human Diversity of Mind' and 'Understanding Scaling of Embodied Cognition.' This project aims to discover and describe functional roles for recently evolved human-specific genetic variants in human-derived cortical organoids. Human-specific variants will be discovered using an innovative computational analysis (a reconstructed ancestral recombination graph) of the genomes of humans and their closest, extinct ancestors – Neanderthals and Denisovans. This approach allows identification of variants that are present in all humans, but absent in the archaic species. Variants present in genes involved in neural development, enriched in this set already, will be prioritized for genetic and functional analysis. Using genome editing of a panel of human-derived iPS cells, this project will re-introduce the extinct archaic variants into various human genetic backgrounds. Each edited iPS line and unedited controls will be assayed for growth, development, and appropriate molecular endophenotypes such as gene expression through stages of cortical organoid induction. Phenotypic deviation from controls may reveal the function roles of the recent genetic innovations in human brain development.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.

人类特有的认知能力以多种形式表现出来。例如，没有其他物种能与人类的言语和语言能力或代际知识积累相媲美。但是，人类特有的大脑进化和认知的遗传基础是什么呢？该项目将对比我们最近灭绝的亲戚（尼安德特人和丹尼索瓦人）的基因组与人类基因组，以确定可能在人类特定大脑进化中发挥作用的遗传变异。基因组学方法将用于将这些基因的古老版本插入人类来源的细胞中。然后将研究携带已灭绝数千年的遗传变异的细胞的生物学，以帮助发现人类大脑发育和认知中最近进化的功能。该项目将提供计算基因组分析和实验基因组操作方面的研究生培训机会。该项目的结果具有引起公众兴趣的巨大潜力，因为它们解决了人类独特性的基本方面，并且该项目可能会通过公共媒体渠道产生广泛传播的机会。此外，该项目可能通过实验描述在早期大脑发育中起作用的基因的功能来为临床和生物医学研究提供信息。拟议的研究丰富了NSF 2026 Idea Machine获奖作品“利用人类思维的多样性”和“理解认知的扩展”。该项目旨在发现和描述最近进化的人类特异性遗传变异在人类衍生的皮质类器官中的功能作用。人类特异性变异将通过对人类及其最接近的灭绝祖先-尼安德特人和丹尼索瓦人的基因组进行创新的计算分析（重建的祖先重组图）来发现。这种方法允许识别存在于所有人类中但在古老物种中不存在的变体。参与神经发育的基因中存在的变体，已经在这组中富集，将优先用于遗传和功能分析。通过对一组人类来源的iPS细胞进行基因组编辑，该项目将把已经灭绝的古老变体重新引入到各种人类遗传背景中。将分析每个编辑的iPS系和未编辑的对照的生长、发育和适当的分子内表型，例如通过皮质类器官诱导阶段的基因表达。与对照组的表型偏差可能揭示了最近基因创新在人类大脑发育中的功能作用。该奖项反映了NSF的法定使命，并被认为值得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来支持。

项目成果

Picroscope: low-cost system for simultaneous longitudinal biological imaging.

• DOI: 10.1038/s42003-021-02779-7
• 发表时间: 2021-11-04
• 期刊: Communications biology
• 影响因子: 5.9
• 作者: Ly VT;Baudin PV;Pansodtee P;Jung EA;Voitiuk K;Rosen YM;Willsey HR;Mantalas GL;Seiler ST;Selberg JA;Cordero SA;Ross JM;Rolandi M;Pollen AA;Nowakowski TJ;Haussler D;Mostajo-Radji MA;Salama SR;Teodorescu M
• 通讯作者: Teodorescu M

Light-weight electrophysiology hardware and software platform for cloud-based neural recording experiments.

• DOI: 10.1088/1741-2552/ac310a
• 发表时间: 2021-11-12
• 期刊: Journal of neural engineering
• 影响因子: 4
• 作者: Voitiuk K;Geng J;Keefe MG;Parks DF;Sanso SE;Hawthorne N;Freeman DB;Currie R;Mostajo-Radji MA;Pollen AA;Nowakowski TJ;Salama SR;Teodorescu M;Haussler D
• 通讯作者: Haussler D

Low cost cloud based remote microscopy for biological sciences

• DOI: 10.1016/j.iot.2021.100454
• 发表时间: 2022-04-20
• 期刊: INTERNET OF THINGS
• 影响因子: 5.9
• 作者: Baudin, Pierre, V;Ly, Victoria T.;Teodorescu, Mircea
• 通讯作者: Teodorescu, Mircea