The African lungfish mucus cocoon is a living tissue with antimicrobial functions

非洲肺鱼粘液茧是具有抗菌功能的活组织

• 批准号: 1938816
• 负责人: Irene Salinas
• 金额: $ 59.13万
• 依托单位: University of New Mexico
• 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: 2020-04-15 至 2024-11-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1938816&HistoricalAwards=false
• 关键词: African; lungfish; mucus; cocoon; living

The transition of vertebrates from aquatic to terrestrial environments was one of the most remarkable steps in evolutionary history. The environmental conditions of land ecosystems imposed new physiological challenges to vertebrates including desiccation stress, UV damage and novel pathogens. Lungfish (Dipnoi), the closest ancestors of all tetrapods, aestivate forming a cocoon that covers their entire body and protects them against external aggressions. This cocoon has been viewed thus far as an inert layer made of glycoproteins. The researchers propose that this cocoon is in fact a living tissue that protects the lungfish against pathogen invasion for long periods of time. The goal of this project is to determine the structure and function of lungfish cocoons from both laboratory animals and animals caught from the wild in Tanzania. Another goal is to identify how the cocoon protects the lungfish from pathogens during aestivation and if specific immune mechanisms are involved. The societal outcomes of this proposal are to establish the US as a global leader in STEM research and education and to level the gender gap in STEM both in the US and Tanzania. This will be achieved by cross-training summer programs targeted to increase women and minorities representation in STEM.This project’s intellectual merit is to investigate novel immunological structures and mechanisms used by vertebrates to adapt to environmental stress. Lungfishes are a good model to answer this question since they can adapt to terrestrial environments under unfavorable conditions. The lungfish cocoon, thought to be an inert mucus layer, has been largely understudied. Preliminary studies indicate that this cocoon may be a living tissue with unique immunological capabilities. Specifically, the researchers hypothesize that the cocoon acts as a living, microbe-trapping structure that utilizes neutrophil extracellular traps (NETs) to halt pathogen invasion during the aestivating months when the lungfish are immobile. A variety of histological, immunological, molecular and sequencing approaches will be used to determine the structure and function of the lungfish cocoon. The immune cells and molecules involved in protection against pathogens in the cocoon will be identified. Laboratory-based experiments will be coupled to field collections. This research has the potential for advances in the fields of evolutionary biology and immunology by characterizing immunological mechanisms that allow lungfish to adapt to dessication stress, a key trait that would allow adaption to terrestrial environments.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.

脊椎动物从水生环境到陆地环境的转变是进化史上最引人注目的步骤之一。陆地生态系统的环境条件对脊椎动物提出了新的生理挑战，包括干燥胁迫、紫外线损伤和新的病原体。肺鱼（Dipnoi）是所有四足动物最接近的祖先，夏眠形成一个茧，覆盖整个身体，保护它们免受外部侵略。迄今为止，这种茧被认为是由糖蛋白组成的惰性层。研究人员提出，这种茧实际上是一种活组织，可以长时间保护肺鱼免受病原体入侵。该项目的目标是确定实验室动物和坦桑尼亚野外捕获动物肺鱼茧的结构和功能。另一个目标是确定茧在夏眠期间如何保护肺鱼免受病原体的侵害，以及是否涉及特定的免疫机制。该提案的社会成果是将美国确立为STEM研究和教育的全球领导者，并缩小美国和坦桑尼亚STEM领域的性别差距。这将通过旨在增加妇女和少数民族在STEM中的代表性的交叉培训夏季项目来实现。该项目的智力价值是研究脊椎动物适应环境压力的新免疫结构和机制。肺鱼是回答这个问题的一个很好的模型，因为它们可以在不利的条件下适应陆地环境。肺鱼的茧被认为是一种惰性的粘液层，在很大程度上还没有得到充分的研究。初步研究表明，这种茧可能是一种具有独特免疫功能的活组织。具体来说，研究人员假设茧作为一种活的微生物捕获结构，利用中性粒细胞胞外陷阱（NET）在肺鱼不动的夏眠月份阻止病原体入侵。将采用多种组织学、免疫学、分子和测序方法来确定肺鱼茧的结构和功能。免疫细胞和分子参与保护免受病原体的茧将被确定。实验室为基础的实验将耦合到现场收集。这项研究通过表征肺鱼适应干燥压力的免疫机制，具有在进化生物学和免疫学领域取得进展的潜力，这是适应陆地环境的关键特征。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。