EiR: Functional Study of the Rapidly Evolving Interferon Complex in Amphibians

EiR：两栖动物中快速进化的干扰素复合物的功能研究

• 批准号: 1831988
• 负责人: Yongming Sang
• 金额: $ 87.86万
• 依托单位: Tennessee State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-15 至 2022-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1831988&HistoricalAwards=false
• 关键词: EiR; Functional; Study; Rapidly; Evolving

Current amphibian decline due to infections is devastating for biodiversity and ecosystem health. Interferons (IFNs) are key immune genes that are important mediators of antitumor and antiviral responses. Understanding the function of amphibian IFNs is fundamental to directly addressing infections that are causing current amphibian declines. This project seeks to understand the signature role of amphibian IFNs in IFN evolution and functional diversification in vertebrates. IFNs originated in jawed fish from the multi-exon progenitors. Recent research by the principal investigator detected the unexpected emergence and expansion of intronless IFN genes in amphibians. This discovery revises the established model of IFN evolution and highlights that amphibians are critical for studying IFN biology in vertebrates. This project will examine the role of the intronless IFNs during frog development and protection against viral infection. Completion of this project will provide a unique and previously unknown platform to address immune evolution, functional capacity, and especially amphibian defense against viral infections. This award will promote collaboration between major research universities and a Historically Black College and University (HBCU). It will provide research training and strengthen biology education at the HBCU. Knowledge regarding the molecular origin and functional diversification of IFN genes in vertebrates is fragmentary. In particular, little is known about amphibian IFNs. Previous studies have discovered only several intron-containing IFN progenitors in amphibians and have underestimated IFN-mediated immune responses in amphibians and the actual role of amphibians in IFN evolution. As a key node in immune evolution, functional understanding of amphibian IFN complex and its reaction to pathogenic infections is fundamental to the study of immunobiology in vertebrates. Using laboratory Xenopus models, the proposed research will (1) comparatively profile the expression of intron-containing and intronless IFN subgroups during frog development and infection, (2) determine the functional capacity and evolutionary superiority of newly evolved intronless IFNs against the viral infection, (3) determine the dependence of amphibian IFN ligands on canonical IFN signaling pathways to induce effector genes and induce antiviral activity. These complimentary contributions will functionally characterize the IFN complex in amphibians, and ultimately fill a knowledge gap in IFN evolution. In addition, the proposed research will integrate collaborative efforts of the PI/Co-PIs at Tennessee State University (TSU), Vanderbilt University, and the University of Rochester to accomplish the objectives. It will train HBCU research personnel at two prominent research institutes and enhance research excellence and broaden STEM education at the minority-serving institution.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.

目前由于感染导致的两栖动物数量下降对生物多样性和生态系统健康是毁灭性的。干扰素（IFNs）是重要的免疫基因，是抗肿瘤和抗病毒反应的重要介质。了解两栖动物ifn的功能是直接解决导致两栖动物数量下降的感染的基础。该项目旨在了解两栖动物IFN在IFN进化和脊椎动物功能多样化中的重要作用。ifn起源于颚鱼的多外显子祖细胞。首席研究员最近的研究发现了两栖动物中无内含子IFN基因的意外出现和扩展。这一发现修正了IFN进化的既定模型，并强调两栖动物对于研究脊椎动物的IFN生物学至关重要。本项目将研究不含内含子的干扰素在青蛙发育和抵御病毒感染中的作用。该项目的完成将为研究免疫进化、功能能力，特别是两栖动物对病毒感染的防御提供一个独特的、以前未知的平台。该奖项将促进主要研究型大学和传统黑人学院和大学（HBCU）之间的合作。它将提供研究培训并加强HBCU的生物学教育。关于脊椎动物中IFN基因的分子起源和功能多样化的知识是不完整的。特别是，人们对两栖动物的干扰素知之甚少。以往的研究仅在两栖动物中发现了几种含内含子的IFN祖细胞，低估了IFN在两栖动物中介导的免疫反应以及两栖动物在IFN进化中的实际作用。作为免疫进化的关键节点，了解两栖动物IFN复合物的功能及其对致病性感染的反应是研究脊椎动物免疫生物学的基础。利用实验室非洲爪蟾模型，本研究将(1)比较分析青蛙发育和感染过程中含内含子和无内含子IFN亚群的表达；(2)确定新进化的无内含子IFN抗病毒感染的功能能力和进化优势；(3)确定两栖动物IFN配体对典型IFN信号通路的依赖，以诱导效应基因和诱导抗病毒活性。这些互补的贡献将在功能上表征两栖动物的IFN复合体，并最终填补IFN进化的知识空白。此外，拟议的研究将整合田纳西州立大学（TSU），范德比尔特大学和罗切斯特大学的PI/ co -PI的合作努力，以实现目标。它将在两所著名的研究机构培训HBCU的研究人员，并在这所为少数族裔服务的机构中提高研究水平，扩大STEM教育。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。

项目成果

Immunometabolic Links Underlying the Infectobesity with Persistent Viral Infections. J

感染性肥胖与持续病毒感染的免疫代谢联系。

• 发表时间: 2019
• 期刊: Journal of immunological sciences
• 作者: Sang, Y.

Integrate structural analysis, isoform diversity, and interferon-inductive propensity of ACE2 to predict SARS-CoV2 susceptibility in vertebrates

• DOI: 10.1016/j.heliyon.2020.e04818
• 发表时间: 2020-09-01
• 期刊: HELIYON
• 影响因子: 4
• 作者: Sang, Eric R.;Tian, Yun;Sang, Yongming
• 通讯作者: Sang, Yongming

Broadening and Strengthening Underrepresented Group Inclusion in Immunological Research

扩大和加强免疫学研究中代表性不足的群体的包容性

• DOI: 10.3389/fimmu.2020.00465
• 发表时间: 2020
• 期刊: Frontiers in Immunology
• 影响因子: 7.3
• 作者: Smolock, Elaine;Robert, Jacques
• 通讯作者: Robert, Jacques

Life-Stage Differences in Microhabitat Use by Hellbenders (Cryptobranchus alleganiensis)

Hellbenders (Cryptobranchus alleganiensis) 使用微生境的生命阶段差异

• 发表时间: 2019
• 期刊: Herpetologica
• 影响因子: 2.4
• 作者: Jeronimo G. Da Silva Neto, William B.

Xenopus Interferon Complex: Inscribing the Amphibiotic Adaption and Species-Specific Pathogenic Pressure in Vertebrate Evolution?

• DOI: 10.3390/cells9010067
• 发表时间: 2019-12
• 期刊: Cells
• 影响因子: 6
• 作者: Yun Tian;Jordan Jennings;Yuanying Gong;Y. Sang