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

合作研究：结构和功能：微环境如何促进防御性共生中的抗菌剂对环境应激的反应

• 批准号: 2247195
• 负责人: Spencer Nyholm
• 金额: $ 45.41万
• 依托单位: University of Connecticut
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2247195&HistoricalAwards=false
• 关键词: Collaborative; Research; Structure; function; How

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.

一些动物与有益的微生物形成关系，产生可以抑制病原体并保护宿主免受疾病的化合物。这些有益的微生物（或共生体）通常对动物至关重要，可以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的风险特别高，这些病原体感染这些卵并杀死发育中的胚胎。因此，一些动物依靠有益的共生体产生有效的抗菌化合物来保护它们的卵。然而，我们缺乏对鸡蛋中的物理、生物和化学因素如何有助于这种保护的了解，这种保护最终可能会避免病原体和气候变化等压力。夏威夷短尾乌贼是研究与细菌有益关系的模型动物。 这项工作将联合收割机结合微生物学，化学和天然产物研究的多学科团队的专业知识，以测试短尾乌贼卵的微环境有助于有益细菌产生有效的抗菌化合物抵御病原微生物的假设。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的影响，并可能导致新的药物发现，使人类受益。 该研究团队还将创建一个新的项目，将交叉培训下一代研究人员在化学，微生物学和有效的科学传播，以帮助我们的国家准备生物经济的领导者。宿主和共生体之间的许多关联是通过产生专门的代谢物和其他防御化合物来介导的。虽然在表征宿主相关微生物群的微生物多样性方面取得了很大进展，但宿主和共生体如何共同努力以实现强大的功能性共生以及它们对环境压力的反应还没有得到很好的理解。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相互作用，以管理防御性共生中的专门代谢物生产。研究人员将（I）确定夏威夷短尾鱿鱼的卵微环境如何有助于抗菌剂的生产和定位，（II）确定温度如何影响对卵中真菌病原体的抗菌反应，以及（III）使用简化的离体实验表征共生体代谢产物的生产，以更好地了解卵的防御功能。它们将靶向已知和新的抗菌代谢物，用于表达分析和离体和卵内定位。这项研究的更广泛意义包括对宿主-微生物协会如何应对全球气温升高和伴随的病原体压力威胁的变革性理解。该团队将通过创建一个新的计划，鱿鱼共生化学（CheSS），将共生和天然产物化学交叉培训学生，从而整合研究和教育。 该研究团队还将参与Skype-A-Scientist计划，接受有效科学传播和公共宣传方面的培训。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。