CAREER: Microbiome regulation by amphibian skin peptides

微生物，包括细菌和真菌，不断与免疫系统相互作用。人们对这种关系如何帮助预防疾病知之甚少。因此，宿主微生物生物学是一个令人兴奋的前沿发现。两栖动物是研究动物宿主和微生物之间共生关系的一个很好的模型系统，因为它们湿润的皮肤表面具有类似于人类消化道和肺部的特性。目前的奖励将使用该模型来测试分泌到北方豹蛙皮肤上的肽是否通过支持有益细菌的生长和抑制致病菌的生长来调节皮肤微生物群。这项研究的结果将为微生物治疗提供信息，并有助于保护工作。由于世界上三分之一的两栖动物物种目前受到威胁，在疾病持续出现损害生物多样性的关键时刻，这项研究还将为两栖动物疾病的管理和保护提供信息。该项目是美国国家科学基金会CAREER奖的核心项目，通过实施微生物组和疾病生态学的指导研究实验室课程，将研究与教育结合起来，提供真实的研究经验。在学习社区中，研究生和博士后研究员将对本科生进行指导。一个由微生物和疾病生态学家、专业教育专家和教师组成的咨询委员会将提供合作和培训。该项目将针对各级代表人数不足的群体进行招聘。在这个合作的环境中，学生将被鼓励设计关于宿主微生物生物学前沿的实验。新出现的传染病威胁着野生动物种群。壶菌病是一种新出现的两栖动物传染病的一个例子，如豹蛙，由真菌壶菌引起。本项目将描述宿主肽和共生微生物在保护宿主免受真菌感染方面的关键相互作用，并确定皮肤防御肽调节微生物组的新机制。中心假设是两栖动物皮肤肽调节皮肤微生物组，从而影响宿主-病原体相互作用。具体目标是：(1)确定在野外和受控中环境条件下皮肤防御肽与微生物群之间的相互作用，包括比较不同肽表达模式的宿主生活史阶段；(2)测试宿主皮肤肽是否支持从宿主分离的微生物（促微生物功能）并抑制潜在的入侵环境微生物（抗菌功能）；(3)通过实验减少皮肤肽，检测不同环境条件下的微生物生态失调，研究防御肽在调节微生物组稳定性中的作用；(4)通过对照实验，研究微生物群落系统发育多样性对宿主皮肤防御肽表达复杂性的影响。确定微生物群在不同环境条件下随时间的变化轨迹，将有助于了解微生物群的组装是随机的、有弹性的，还是随着防御肽的再生而自适应地发生变化。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Microbes, including bacteria and fungi, are in constant interaction with the immune system. Little is known about how this relationship helps prevent disease. Thus host-microbe biology is an exciting frontier for discovery. Amphibians are an excellent model system to study the symbiotic relationships between animal hosts and microbes because their moist skin surfaces have properties similar to the human digestive tract and lungs. The current award will use this model to test whether peptides secreted onto the skin of the northern leopard frog regulate skin microbiota by supporting the growth of beneficial bacteria and by inhibiting the growth of pathogenic bacteria. The results of this study will inform microbial therapies and contribute to conservation efforts as well. Since one third of the world's amphibian species are currently threatened, this research will also inform amphibian disease management and conservation at a critical time when continued disease emergence is harming biodiversity. Central to the NSF CAREER award, this project integrates research with education by implementing a Mentored Research Lab course on Microbiome and Disease Ecology to provide authentic research experiences. In learning communities, graduate students and postdoctoral researchers will give mentorship to undergraduates. An advisory board of microbial and disease ecologists, professional education specialists, and faculty will provide collaboration and training. The project will target recruitment from underrepresented groups at all levels. In this collaborative setting, students will be encouraged to design experiments on the cutting edge of host-microbe biology. Emerging infectious diseases threaten wildlife populations. Chytridiomycosis is one example of an emerging infectious disease of amphibians, such as leopard frogs, and is caused by the fungus Batrachochytrium dendrobatidis. This project will describe key interactions of host peptides and symbiotic microbes for defending the host against fungal infections and identify a novel mechanism of microbiome regulation by skin defense peptides. The central hypothesis is that amphibian skin peptides regulate the skin microbiome, thus impacting host-pathogen interactions. Specific objectives are: (1) Identify interactions between skin defense peptides and microbiota under field and controlled mesocosm conditions including comparisons among host life-history stages with different peptide expression patterns, (2) test if host skin peptides support microbes isolated from hosts (promicrobial function) and inhibit potentially invasive environmental microbes (antimicrobial function), (3) examine the role of defense peptides in regulating microbiome stability by experimentally reducing skin peptides and testing for microbial dysbiosis under different environmental conditions, and (4) test the role of microbial community phylogenetic diversity prompting complexity of host defense peptide expression on the skin through controlled experiments. Determining the trajectory of the microbiota through time under different environmental conditions will provide insight on whether microbiome assembly is stochastic, resilient, or adaptively shifts as defense peptides regenerate.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.