Collaborative Research: Immune tradeoffs during tissue regeneration in mammals

合作研究：哺乳动物组织再生过程中的免疫权衡

• 批准号: 1353857
• 负责人: Vanessa Ezenwa
• 金额: $ 29万
• 依托单位: University of Georgia Research Foundation Inc
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-15 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1353857&HistoricalAwards=false
• 关键词: Collaborative; Research; Immune; tradeoffs; during

Why can salamanders re-grow amputated limbs but humans cannot? Understanding the mechanisms that favor tissue regeneration in lieu of tissue repair remains one of the great unanswered questions in biology. A particularly intriguing hypothesis, though poorly investigated, is that the loss of regenerative capacity in higher vertebrates coincides with the presence of a strong adaptive immune response. Now, the recent discovery of complete tissue regeneration in wild African spiny mice (Acomys) compared to the failure to regenerate in a co-occurring rodent (Myomyscus), allows a comprehensive examination of the links between immunity and regeneration in wild, pathogen-exposed, and fully immunocompetent adult mammals. Specifically, this study tests the hypothesis that tradeoffs in immunity along (1) innate vs. adaptive and (2) pro vs. anti-inflammatory axes underlie variation in the ability and rate of regeneration between these wild species. Quantifying immune and inflammatory changes at the cellular and molecular level in response to injury is expected to reveal a bias towards innate immunity and anti-inflammatory molecules in regenerators, and a shift towards adaptive immunity and pro-inflammatory responses in non-regenerators. Project results will provide fundamental insight into the mechanisms that constrain regenerative ability in mammals. Because regeneration biology is a fascinating topic with great potential to excite students about science, the investigators will engage U.S. and international students of all ages in the project. Graduate and undergraduate students from the U.S. will travel to Kenya, where animal work will take place, to actively participate in the study and collaborate with Kenyan students and scientists. The project team will also make a series of visits to a local Kenyan girls' secondary school and a primary school to showcase basic concepts in regeneration biology using African spiny mice as a tool. The international component of this study is co-supported by NSF's Office of International and Integrative Activities.

为什么蝾螈可以再生截肢，而人类不能？了解有利于组织再生而不是组织修复的机制仍然是生物学中未回答的重大问题之一。 一个特别有趣的假说，虽然研究不足，是高等脊椎动物再生能力的丧失与强烈的适应性免疫反应的存在相吻合。 现在，最近发现的完整组织再生的野生非洲多刺小鼠（Acomys）相比，未能再生的共同发生的啮齿动物（Myomyscus），允许全面检查免疫和再生之间的联系，在野生，病原体暴露，完全免疫活性的成年哺乳动物。 具体而言，本研究检验了以下假设，即免疫沿着（1）先天与适应性和（2）促炎与抗炎轴的权衡是这些野生物种之间再生能力和速率变化的基础。 在细胞和分子水平上定量响应于损伤的免疫和炎症变化预计将揭示再生者对先天免疫和抗炎分子的偏好，以及非再生者对适应性免疫和促炎反应的转变。 项目结果将为限制哺乳动物再生能力的机制提供基本的见解。 由于再生生物学是一个迷人的话题，有很大的潜力激发学生对科学的兴趣，研究人员将吸引所有年龄段的美国和国际学生参与该项目。 来自美国的研究生和本科生将前往肯尼亚，在那里将进行动物工作，积极参与研究，并与肯尼亚学生和科学家合作。 项目小组还将对肯尼亚当地的一所女子中学和一所小学进行一系列访问，以展示利用非洲刺鼠作为工具的再生生物学基本概念。 本研究的国际部分由NSF的国际和综合活动办公室共同支持。