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: 2247196
• 负责人: Marcy Balunas
• 金额: $ 46.99万
• 依托单位: Regents of the University of Michigan - Ann Arbor
• 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=2247196&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，并且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因病原体感染这些卵并杀死发展胚胎而面临特别高的风险。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其卵。但是，我们对卵中的物理，生物学和化学因子在这种保护中的贡献最终如何避免了病原体和气候变化等压力。夏威夷牛尾鱿鱼已成为研究与细菌有益关系的模型动物。 这项工作将结合一个多学科团队在微生物，化学和天然产品研究中的专业知识，以检验以下假设：bobtail鱿鱼的微环境有助于有益细菌产生有效的抗微生物化合物，以防御病原微生物。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的影响，并可能导致新的药物发现可以使人类受益。 研究团队还将创建一个新的计划，该计划将在化学，微生物学和有效的科学沟通方面跨越下一代研究人员，以帮助我们的国家为领导者提供生物经济学的准备。宿主和symbionts之间的许多关联是通过生产专业的代谢物和其他防御性化合物来介导的。尽管在表征与宿主相关的微生物群的微生物多样性方面取得了长足的进步，但宿主和共生体如何共同努力以实现强大的功能共生性及其对环境压力的反应并不理解。这项工作将使用一套多学科工具来了解在防御性共生中如何与环境进行专门代谢物生产的环境接口。研究人员将（i）确定夏威夷圆形鱿鱼的鸡蛋微环境，euprymna scolopes，有助于抗菌生产和本地化，（ii）确定温度如何影响抗菌对Ovum中真菌病原体的反应，以及（III）使用Symbiont Defentions使用Simplite Simplitient of ofo viv viv的实验来实验。它们将靶向已知的和新的抗菌代谢物，用于表达分析和定位在体内以及卵子中。这项研究的更广泛的含义包括对宿主 - 微生物关联如何应对增加全球温度和伴随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计划，鱿鱼共生化学（国际象棋）来整合研究和教育，该计划将跨越共生和自然产品化学的学生。 研究团队还将与Skype-A-Scientist计划互动，以接受有关有效的科学沟通和公共宣传的培训。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的知识分子优点和更广泛影响的评估审查标准通过评估来获得支持的。