Collaborative Research: Structure and function: How microenvironment facilitates antimicrobial response to environmental stress in a defensive symbiosis

一些动物与有益的微生物形成关系，这些微生物产生的化合物可以抑制病原体并保护宿主免受疾病的侵袭。这些有益的微生物(或共生体)通常对动物至关重要，并可能影响整个物种和生态系统的健康。在环境中产卵的动物受到病原体感染并杀死发育中的胚胎的风险特别高。因此，一些动物依靠有益的共生体来保护它们的卵，这些共生体能产生强大的抗菌化合物。然而，我们缺乏对鸡蛋中的物理、生物和化学因素如何起到这种保护作用的了解，这种保护最终可能会延缓病原体和气候变化等压力。夏威夷短尾乌贼一直是研究与细菌有益关系的模型动物。这项工作将结合微生物学、化学和天然产品研究方面的多学科团队的专业知识，以检验以下假设：短尾鱿鱼卵的微环境有助于有益细菌产生有效的抗菌化合物，从而抵御病原微生物。了解这些保护机制将揭示有益细菌如何保护动物免受环境压力，并可能导致新的药物发现，使人类受益。研究团队还将创建一个新的项目，对下一代研究人员进行化学、微生物学和有效科学交流方面的交叉培训，以帮助我国为生物经济培养领导者。宿主和共生体之间的许多联系是通过产生专门的代谢物和其他防御性化合物来调节的。尽管在表征寄主相关微生物区系的微生物多样性方面已经取得了很大的进展，但寄主和共生体如何协同工作以实现强大的功能共生以及它们对环境胁迫的响应还不是很清楚。这项工作将使用一套多学科工具来了解物理、化学和生物参数如何与环境交互作用，以管理防御性共生中的专门代谢物生产。研究人员将(I)确定夏威夷短尾乌贼(Euprymna Scolope)的卵微环境如何有助于抗菌剂的产生和定位，(Ii)确定温度如何影响卵子对真菌病原体的抗菌剂反应，以及(Iii)利用简化的体外实验表征共生体代谢物的产生，以更好地了解卵子的防御功能。他们将针对已知和新的抗微生物代谢物进行体外和卵子内的表达分析和定位。这项研究的更广泛的影响包括对宿主-微生物协会如何应对全球气温上升和伴随的病原体压力的威胁的变革性理解。该团队将通过创建一个新的项目--鱿鱼共生化学(CHESS)来整合研究和教育，该项目将对学生进行共生和天然产品化学的交叉培训。研究团队还将参与Skype-A-Science计划，以接受有效的科学交流和公共出行方面的培训。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。

Some animals form relationships with beneficial microbes that produce compounds that can inhibit pathogens and protect the host from disease. These beneficial microbes (or symbionts) are often critical for the animals and can influence the health of whole species and ecosystems. Animals that lay their eggs in the environment are at a particularly high risk from pathogens infecting these eggs and killing developing embryos. Therefore, some animals rely on beneficial symbionts that produce potent antimicrobial compounds to protect their eggs. However, we lack an understanding of how physical, biological, and chemical factors in eggs contribute to this protection that ultimately may stave off stresses such as pathogens and climate change. The Hawaiian bobtail squid has served as a model animal to study beneficial relationships with bacteria. This work will combine the expertise of a multidisciplinary team in microbiology, chemistry, and natural products research to test the hypothesis that the microenvironment of bobtail squid eggs helps beneficial bacteria produce effective antimicrobial compounds that defend against pathogenic microbes. Understanding these protective mechanisms will reveal how beneficial bacteria protect animals from environmental stress and may lead to new drug discoveries that can benefit humans. The research team will also create a new program that will cross-train the next generation of researchers in both chemistry, microbiology, and effective scientific communication to help our country prepare leaders for the bioeconomy.Many associations between hosts and symbionts are mediated via the production of specialized metabolites and other defensive compounds. Although great strides have been made in characterizing the microbial diversity of host-associated microbiota, how hosts and symbionts work together to achieve robust functional symbioses and their response to environmental stress is not well understood. This work will use a suite of multidisciplinary tools to understand how physical, chemical, and biological parameters interface with the environment to govern specialized metabolite production in a defensive symbiosis. The investigators will (I) determine how the egg microenvironment of the Hawaiian bobtail squid, Euprymna scolopes, contributes to antimicrobial production and localization, (II) determine how temperature influences antimicrobial response to fungal pathogens in ovum, and (III) characterize symbiont metabolite production using simplified ex vivo experiments to better understand in ovum defensive function. They will target known and new antimicrobial metabolites for expression analyses and localization ex vivo and in ovum. Broader implications of this research include transformative understanding of how host-microbe associations respond to threats of increasing global temperatures and concomitant pathogen stress. The team will integrate research and education by creating a new program, Chemistry of Squid Symbiosis (CheSS), that will cross-train students in symbiosis and natural product chemistry. The research team will also engage with the Skype-A-Scientist program to receive training on effective scientific communication and public outreach.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.