EDGE CT: Catalyzing regeneration research by developing functional tools for post-embryonic stages

EDGE CT：通过开发胚胎后阶段的功能工具来催化再生研究

• 批准号: 1923429
• 负责人: Alexandra Bely
• 金额: $ 93.53万
• 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: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1923429&HistoricalAwards=false
• 关键词: EDGE; CT; Catalyzing; regeneration; research

Injury is widespread in nature and animals possess varied mechanisms to cope with damage or the loss of body parts. One of the most dramatic injury responses known is regeneration, the regrowing of a body part that has been lost. Although this ability is quite limited in some animals, such as mammals, many others are able to regenerate extensive parts of their body. Technical challenges have severely limited the study of the genes involved in regeneration in some of the most highly regenerative animals. Annelids, or segmented worms, include numerous highly regenerative species but there are no robust approaches for studying the genetic basis of regeneration in this group. The team of investigators of this project develop new approaches for testing the function of genes during regeneration in three highly regenerative annelid species. This work will open up the possibility of identifying the genes and molecular pathways responsible for the remarkable regenerative abilities of annelid worms, and is expected to help catalyze research in other groups of animals. Technical advances are shared broadly with relevant research communities through roundtable discussions at scientific conferences, a laboratory-based hands-on workshop, a project blog, and other online forums. The team of investigators also develop and disseminate general educational resources about regeneration and its study, including an educational comic book and teaching materials for high school science teachers and students. This project addresses a central technical challenge for studying regeneration in many animal groups: manipulating gene function in post-embryonic life-history stages. The project is executed by a close-knit team of researchers and focuses on developing functional approaches to interrogate the genotype-phenotype relationship in three focal annelid species with distinct life histories and adult growth patterns: Platynereis, Capitella, and Pristina. In Aim 1, post-embryonic delivery techniques are optimized using a combination of injection and electroporation. In Aim 2, knock-down approaches using morpholinos and siRNAs in post-embryonic stages are developed, and in Aim 3, gene knock-ins and knock-outs in post-embryonic stages using CRSPR/Cas9 are developed. The work is expected to have a strong catalyzing effect on research, with an increase in the power of inquiry in these other soft-bodied and vermiform animals for existing research labs, an increase in the number of research labs utilizing such organisms and tools.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.

损伤在自然界中广泛存在，动物拥有各种机制来科普身体部位的损伤或损失。已知的最引人注目的损伤反应之一是再生，即身体失去的部分重新生长。虽然这种能力在某些动物中非常有限，例如哺乳动物，但许多其他动物能够再生身体的大部分。技术挑战严重限制了对一些再生能力最强的动物中参与再生的基因的研究。环节动物，或分节蠕虫，包括许多高度再生的物种，但没有强大的方法来研究这组再生的遗传基础。该项目的研究人员团队开发了新的方法来测试三种高度再生环节动物物种再生过程中基因的功能。这项工作将为确定环节动物蠕虫非凡再生能力的基因和分子途径开辟可能性，并有望帮助催化其他动物群体的研究。通过科学会议上的圆桌讨论、基于实验室的实践研讨会、项目博客和其他在线论坛，与相关研究团体广泛分享技术进步。调查小组还开发和传播有关再生及其研究的一般教育资源，包括教育漫画书和高中科学教师和学生的教材。该项目解决了研究许多动物群体再生的核心技术挑战：在胚胎后生活史阶段操纵基因功能。该项目由一个紧密团结的研究团队执行，重点是开发功能方法，以询问三个焦点环节动物物种的基因型-表型关系，具有不同的生活史和成年生长模式：Platynereis，Capitella和普里什蒂纳。在目标1中，使用注射和电穿孔的组合优化胚胎后递送技术。在目标2中，开发了在胚胎后阶段使用吗啉代和siRNA的敲除方法，并且在目标3中，开发了在胚胎后阶段使用CRSPR/Cas9的基因敲入和敲除。这项工作预计将对研究产生强烈的催化作用，增加现有研究实验室对这些其他软体动物和蠕虫状动物的研究能力，增加使用这些生物和工具的研究实验室的数量。该奖项反映了NSF的法定使命，并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，被认为值得支持。