EDGE: Expanding the functional genetics toolkit to link genes to phenotypes in cichlid fish

EDGE：扩展功能遗传学工具包，将慈鲷的基因与表型联系起来

• 批准号: 1825723
• 负责人: Scott Juntti
• 金额: $ 30万
• 依托单位: University of Maryland, College Park
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1825723&HistoricalAwards=false
• 关键词: EDGE; Expanding; functional; genetics; toolkit

How does the genome encode the information for proper development and function of the body? This important question is technically and ethically difficult to address in humans, and there is a need for additional animal models that can support gaining this foundational understanding. The cichlid fish are an excellent system to use because these species have wide variation in anatomy, physiology, and behavior. Because their genomes have been sequenced recently, correlations between animal features and gene sequences can be determined. However, the causal links between gene sequence and function must be tested directly to gain meaningful understanding. Causal testing of the links requires the development and deployment of new technologies. The work supported by this grant develops the tools to obtain cichlid embryos and modify gene sequences, enabling researchers to understand how specific genes control the form and function of the body. Given that cichlids and humans share most of the same genes, this work should allow new insights into how genes function in health and disease. The work also allows many opportunities for undergraduate researches from diverse backgrounds to participate directly in the research enterprise, and it includes workshops for investigators from other institutions to enable them to adopt the new protocols and tools in their own research programs.The 2000 species of cichlid fish exhibit a stunning variety of phenotypes in morphology, physiology, and behavior. Genome-wide scans have mapped these traits to candidate genetic loci. However, functional genetic manipulations are required for direct tests of gene function, and technology for such experiments has lagged behind. CRISPR/Cas has emerged as a potent gene editing tool, and proof-of-principle experiments have been performed in two cichlid species. The work of this grant involves development of experimental pipelines that enable gene editing experiments in a wider variety of cichlid species. Specifically, hormonal treatment regimens that support the reproductive cycle of cichlids and derivation of fertilized eggs are identified, and protocols that permit the modification of genes in a variety of species, through creation of loss-of-function mutations and the insertion of species-specific sequence variants into other species, are developed. Insights and knowledge obtained through these efforts are shared with the broader community through workshops, websites, and publications. Together, the newly developed approaches will support the study of genetic variation and its effects on form and function.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.

基因组如何编码身体正常发育和功能所需的信息？在人类身上，这个重要的问题在技术上和伦理上都很难解决，需要更多的动物模型来支持获得这种基础性的理解。慈鱼是一个很好的系统，因为这些物种在解剖学、生理学和行为上都有很大的差异。因为它们的基因组最近已经被测序，所以可以确定动物特征和基因序列之间的相关性。然而，必须直接测试基因序列和功能之间的因果联系，才能获得有意义的理解。对这些联系进行因果检验需要开发和部署新技术。这项由这笔赠款支持的工作开发了获得慈济鱼胚胎和修改基因序列的工具，使研究人员能够了解特定基因如何控制身体的形式和功能。考虑到慈鱼和人类拥有大部分相同的基因，这项工作应该会让人们对基因如何在健康和疾病中发挥作用有新的见解。这项工作还允许来自不同背景的本科生研究人员有许多机会直接参与研究事业，它还包括为来自其他机构的研究人员举办研讨会，使他们能够在自己的研究计划中采用新的方案和工具。2000种慈鱼在形态、生理和行为方面表现出惊人的多样性。全基因组扫描已经将这些特征映射到候选遗传位点。然而，基因功能的直接测试需要功能基因操作，而此类实验的技术已经落后。CRISPR/Cas已成为一种强有力的基因编辑工具，并已在两种慈鱼身上进行了原理验证实验。这笔赠款的工作包括开发实验管道，使基因编辑实验能够在更多种类的慈鱼物种中进行。具体地说，确定了支持线虫繁殖周期和受精卵衍生的激素治疗方案，并制定了允许通过创建功能丧失突变和将物种特有的序列变体插入其他物种来修改各种物种的基因的方案。通过这些努力获得的见解和知识通过研讨会、网站和出版物与更广泛的社区分享。总之，新开发的方法将支持遗传变异及其对形式和功能的影响的研究。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。

项目成果

The Future of Gene-Guided Neuroscience Research in Non-Traditional Model Organisms

• DOI: 10.1159/000500072
• 发表时间: 2019-01-01
• 期刊: BRAIN BEHAVIOR AND EVOLUTION
• 影响因子: 1.7
• 作者: Juntti, Scott

Modular genetic control of social status in a cichlid fish

• DOI: 10.1073/pnas.2008925117
• 发表时间: 2020-11-10
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Alward, Beau A.;Laud, Vibhav A.;Fernald, Russell D.
• 通讯作者: Fernald, Russell D.