X-KINGDOM-MIF - Cross-kingdom analysis of macrophage migration inhibitory factor (MIF) functions

X-KINGDOM-MIF - 巨噬细胞迁移抑制因子（MIF）功能的跨界分析

• 批准号: 316495857
• 负责人: Professor Dr. Jürgen Bernhagen
• 金额: --
• 依托单位: UMR - Interactions Plantes-Microorganismes et Sante Vegetale
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/316495857?language=en
• 关键词: KINGDOM; MIF; Cross; kingdom; analysis

The chemokine-like mediator macrophage migration inhibitory factor (MIF) is a prominent human disease marker and a pivotal mediator of inflammatory, infectious and immune diseases including septic shock, colitis, malaria, rheumatoid arthritis, and atherosclerosis, as well as tumorigenesis. Translational applications emerging from MIF research have been delayed because of an incomplete mechanistic understanding of MIF´s pathobiology. Strikingly, MIF is an evolutionarily conserved protein that is found across kingdoms. Despite of its limited molecular size and lack of appreciable modular domains, MIF has been found to exhibit several sequential and three-dimensional structural motifs including two catalytic sites that provide this protein with a surprising functional complexity. In recent years, the applicants have significantly contributed to the elucidation of MIF structure and its role in human and plant disease and have performed comprehensive in silico characterization of plant MIFs. In the context of these findings, it is the aim of this joint ANR-DFG proposal to study the molecular links between MIF of human, plant and parasite (aphid) origin to identify potentially conserved functions in the regulation of immune responses between kingdoms. The applicants combine expert knowledge in immune regulatory mechanisms of human MIF and insect pathobiology as well as long-standing expertise in comparative plant immunity and molecular genetics of Arabidopsis thaliana and barley to study MIF functional and structural features in this cross-species/kingdom approach. They thus represent a unique interdisciplinary team combining in-depth expertise on MIF biochemistry, biology, and pathobiology, with plant genetics and biotechnology and infectious disease research. The collaborative project will enable us to shed first light on the role of plant and insect MIFs and on the functional relevance of the shared versus distinct motifs between the different kingdoms. We will systematically utilize the cross-kingdom analysis of MIF´s structure-function profile to better understand the mechanisms of MIF in infectious disease and plant immunity. In addition, the proposal will spark novel research into immune evasion mechanisms and evolutionary history of the MIF family.

趋化因子样介质巨噬细胞迁移抑制因子（MIF）是一种重要的人类疾病标志物，也是炎症、感染性和免疫疾病（包括脓毒性休克、结肠炎、疟疾、类风湿性关节炎和动脉粥样硬化）以及肿瘤发生的关键介质。由于对 MIF 病理学的机制理解不完整，MIF 研究出现的转化应用已被推迟。引人注目的是，MIF 是一种进化上保守的蛋白质，在各个王国中都有发现。尽管其分子大小有限且缺乏明显的模块结构域，但人们发现 MIF 表现出几个连续的三维结构基序，包括两个催化位点，这为该蛋白质提供了令人惊讶的功能复杂性。近年来，申请人对MIF结构及其在人类和植物疾病中的作用的阐明做出了重大贡献，并且对植物MIF进行了全面的计算机表征。在这些发现的背景下，ANR-DFG 联合提案的目的是研究人类、植物和寄生虫（蚜虫）来源的 MIF 之间的分子联系，以确定王国之间免疫反应调节中潜在的保守功能。申请人结合了人类 MIF 免疫调节机制和昆虫病理学方面的专业知识，以及拟南芥和大麦的比较植物免疫和分子遗传学方面的长期专业知识，以这种跨物种/界的方法研究 MIF 的功能和结构特征。因此，他们代表了一个独特的跨学科团队，将 MIF 生物化学、生物学和病理学方面的深入专业知识与植物遗传学和生物技术以及传染病研究相结合。该合作项目将使我们能够首次阐明植物和昆虫 MIF 的作用，以及不同领域之间共享与独特基序的功能相关性。我们将系统地利用MIF结构功能谱的跨领域分析来更好地理解MIF在传染病和植物免疫中的机制。此外，该提案还将引发对 MIF 家族免疫逃避机制和进化史的新研究。

项目成果

A cross‐kingdom view on the immunomodulatory role of MIF/D‐DT proteins in mammalian and plant Pseudomonas infections

MIF/DâDT 蛋白在哺乳动物和植物假单胞菌感染中的免疫调节作用的跨界观点

• DOI: 10.1111/imm.13480
• 期刊: Immunology
• 影响因子: 6.4
• 作者: Panstruga R;Donnelly SC;Bernhagen J
• 通讯作者: Bernhagen J

Evaluation of dsRNA delivery methods for targeting macrophage migration inhibitory factor MIF in RNAi-based aphid control

基于 RNAi 的蚜虫控制中靶向巨噬细胞迁移抑制因子 MIF 的 dsRNA 递送方法的评估

• DOI: 10.1007/s41348-021-00464-9
• 发表时间: 2021
• 期刊: Journal of Plant Diseases and Protection
• 影响因子: 2
• 作者: Ladera-Carmona MJ;Poranen MM;van Bel Aart J.E;Kogel K-H;Imani J
• 通讯作者: Imani J

Cross-Kingdom Analysis of Diversity, Evolutionary History, and Site Selection within the Eukaryotic Macrophage Migration Inhibitory Factor Superfamily

• DOI: 10.3390/genes10100740
• 发表时间: 2019-09
• 期刊: Genes
• 影响因子: 3.5
• 作者: C. Michelet;E. Danchin;M. Jaouannet;J. Bernhagen;R. Panstruga;K. Kogel;H. Keller;C. Coustau

Cross-kingdom mimicry of the receptor signaling and leukocyte recruitment activity of a human cytokine by its plant orthologs

植物直向同源物对人类细胞因子的受体信号传导和白细胞募集活性的跨界模拟

• DOI: 10.1074/jbc.ra119.009716
• 发表时间: 2020
• 期刊: The Journal of Biological Chemistry
• 作者: Sinitski D;Gruner K;Brandhofer M;Kontos C;Winkler P;Reinstädler A;Bourilhon P;Xiao Z;Cool R;Kapurniotu A;Dekker FJ;Panstruga R;Bernhagen J
• 通讯作者: Bernhagen J

Studying Plant MIF/D-DT-Like Genes and Proteins (MDLs).

• DOI: 10.1007/978-1-4939-9936-1_22
• 发表时间: 2020
• 期刊: Methods in molecular biology
• 作者: Dzmitry Sinitski;Katrin Gruner;J. Bernhagen;R. Panstruga