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EDGE: Tools for studying gene function in voles

EDGE：研究田鼠基因功能的工具

基本信息

批准号：
1827790
负责人：
Zoe Donaldson
金额：
$ 160万
依托单位：
University of Colorado at Boulder
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 2023-08-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1827790&HistoricalAwards=false
关键词：
EDGE Tools studying gene function

项目摘要

Different rodent species live in all parts of the world and lead various lifestyles from a solitary existence to taking part in complex societies. As a result, rodents are useful for investigating the biological explanations underlying different social behaviors in different species. The goal of this project is to develop the tools and resources needed to discover the genes that contribute to behavioral diversity. The investigators focus on two vole species that differ dramatically in their social behavior, monogamous prairie voles and polygamous meadow voles. They develop methods to alter genes in these animals, deliver new genetic material to the brain by intravenous injection, and manipulate genes in particular brain regions and cell types. These tools are made available to the broader scientific community via online resource dissemination, presentations at national meetings, local workshops, and hands-on lab sessions with the goal of extending these tools to scientists studying other rodent species. In addition, the investigators incorporate undergraduate, graduate, and post-doctoral trainees in the development process, generating a cohort of scientists who are versed in understanding the impact of genes on behavior.One goal of biological investigation is to understand the organizing principles of natural variation. To accomplish this goal requires causal manipulations of non-traditional model species. Wild rodents offer opportunities to pursue such research. They are behaviorally diverse, yet allow researchers to use many of the same tools developed for model organisms. Voles of the genus Microtus stand out as popular study subjects. They vary in mating system, social attachment, and other behaviors that cannot be studied in traditional laboratory species. This project addresses a current bottleneck in integrative research with voles: the lack of technologies to directly interrogate neurogenetic function. To address this, the team of three investigators: 1) Optimize tools for germline manipulation of Microtus embryos; 2) Develop an intravenously deliverable genetic vector; and 3) Test methods for post-mitotic gene manipulation in cells and regulatory circuits. The team disseminates these advances via national meetings, workshops, trainee exchanges, and online resources. The investigators also train undergraduate, graduate, and post-doctoral researchers, developing a cohort of scientists versed in these technologies. Initial proof-of-concept manipulations focuses on oxytocin and vasopressin systems, and the materials generated are of immediate use to the vole research community. However, the challenges addressed are similar to those faced in other non-model rodents; developing these tools promises to transform the integrative study of genes and behavior more generally.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.

不同的啮齿动物物种生活在世界各地，从孤独的生活到参与复杂的社会，都有不同的生活方式。因此，啮齿动物有助于研究不同物种不同社会行为背后的生物学解释。该项目的目标是开发所需的工具和资源，以发现有助于行为多样性的基因。研究人员专注于两种在社会行为上截然不同的田鼠，一夫一妻制的草原田鼠和一夫多妻制的草甸田鼠。他们开发出改变这些动物基因的方法，通过静脉注射将新的遗传物质输送到大脑，并操纵特定脑区和细胞类型的基因。这些工具通过在线资源传播、在国家会议上的演讲、地方研讨会和动手实验室会议向更广泛的科学界提供，目的是将这些工具扩展到研究其他啮齿动物物种的科学家。此外，研究人员将本科生、研究生和博士后实习生纳入开发过程，产生了一批精通基因对行为影响的科学家。生物学调查的目标之一是了解自然变异的组织原理。为了实现这一目标，需要对非传统模式物种进行因果操作。野生啮齿动物提供了进行此类研究的机会。它们在行为上是不同的，但允许研究人员使用许多为模型生物体开发的相同工具。田鼠属的田鼠是最受欢迎的研究对象。它们在交配系统、社会依恋和其他无法在传统实验室物种中研究的行为上存在差异。该项目解决了目前田鼠综合研究中的一个瓶颈：缺乏直接询问神经遗传功能的技术。为了解决这一问题，由三名研究人员组成的团队：1)优化田鼠胚胎胚系操作的工具；2)开发一种静脉递送的遗传载体；以及3)细胞和调控电路中有丝分裂后基因操作的测试方法。该小组通过国家会议、讲习班、实习生交流和在线资源传播这些进展。研究人员还培训本科生、研究生和博士后研究人员，培养一批精通这些技术的科学家。最初的概念验证操作侧重于催产素和后叶加压素系统，产生的材料立即用于田鼠研究社区。然而，解决的挑战与其他非模型啮齿动物面临的挑战相似；开发这些工具有望更广泛地改变基因和行为的综合研究。该奖项反映了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。