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.

类似趋化因子的介体巨噬细胞迁移抑制因子（MIF）是一个突出的人类疾病标志物，是炎性，传染和免疫学疾病的关键介体，包括败血性休克，结肠炎，疟疾，类风湿关节炎和动脉粥样硬化以及肿瘤。由于对MIF病原体学的机理不完全理解，MIF研究中出现的翻译应用已被推迟。令人惊讶的是，MIF是一种进化构成的蛋白质，在跨国遍布。尽管MIF的分子大小有限，并且缺乏可欣赏的模块化结构域，但仍发现MIF暴露了几个顺序和三维结构基序，包括两个催化位点，这些催化位点为该蛋白提供了令人惊讶的功能复杂性。近年来，申请人显着促进了MIF结构及其在人类和植物疾病中的作用，并在植物MIF的硅特征方面进行了全面的作用。在这些发现的背景下，该联合ANR-DFG提案的目的是研究人类，植物和寄生虫（蚜虫）起源的MIF之间的分子联系，以识别在调节王国之间免疫调查的可能构成的功能。申请人结合了人类MIF免疫调节机制的专家知识和隔热病理学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，以研究这种交叉种群/王国的MIF功能和结构特征。因此，它们代表了一个独特的跨学科团队，结合了MIF生物化学，生物学和病理生物学的深入专家，以及植物遗传学以及生物技术和传染病研究。该协作项目将使我们能够首先阐明植物和昆虫MIF的作用，以及不同王国之间共享与不同主题的功能相关性。我们将系统地利用MIF结构功能概况的跨王朝分析，以更好地了解MIF在传染病和植物免疫史中的机制。此外，该提案将引发对MIF家族的免疫避免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