个人简介
工作经历
2012.12至今 中国农业大学 教授
2010.6–2012.12 中国农业大学 副教授
2006.9- 2010.8 英国MRC-NIMR CDF
2002.7- 2010.3 中科院生物物理所 助研,副研
2000.7- 2002.7 中科院生物物理所 博士后
教育经历
1989.9-1993.7 河北农业大学 本科
1993.9-1996.7 中国农业科学院研究生院 硕士
1996.9-2000.7 中国农业大学 博士
科研项目
主持或参加国家自然科学基金、科技部、教育部等项目。
近年主持项目
国家自然科学基金面上项目,31772112 ,稻瘟病菌MoTps1的底物结合机制及其特异性 抑制剂的筛选 2018.01-2021.12
国家自然科学基金面上项目,31571990 , 水稻抗病蛋白Pia RATX1 结构域与稻瘟病菌效应因子相互作用的结构基础 2016.01-2019.12
国家自然科学基金面上项目,31171800,稻瘟病菌转录因子MoPCG2p的晶体结构解析 2012.01-2015.12
重点研发计划“化学肥料和农药减施增效综合技术研发”专项的,2017YFD0200500, 农业生物药物分子靶标发现与绿色药物分子设计 2017.7-2020.12
973 项目, 2012CB114000, 主要粮食作物重大病害控制的基础研究,2012/01-2016/ 12
新世纪人才 2012年, 已结题,主持
奖励情况
2012 教育部新世纪人才
研究领域
种植抗病品种是作物病害防治最为经济有效的措施。抗病基因的发掘和改造是进行抗病育种的基石。化学防治是病害防治最后一道防线,开发绿色环境友好的新型高效农药是农业安全生产的迫切需要。以水稻与稻瘟病菌为模式体系,基于结构生物学手段开展植物与病原物相互作用结构机制的研究以指导抗病基因改良和绿色农药设计。
1. 植物NLR类型免疫受体基于结构的人工设计和抗病分子育种
植物存在与动物相似的定位于胞质的NLR类型免疫受体。植物的NLR类型免疫受体识别效应蛋白,解除效应蛋白对基础免疫反应的抑制和重新激活免疫反应。编码NLR类型免疫受体的基因是植物的主要抗性资源。研究胞内免疫受体识别病原物效应蛋白的分子机制不仅有助于我们理解动植物免疫机理提供重要线索,而且为抗病分子育种提供新的材料和思路。
解析水稻免疫受体重金属结合区域(HMA)及其与效应蛋白复合物的结构,阐明受体识别效应蛋白的结构机制(PNAS 2018, Acta F 2015,2018),为基于结构来设计新型识别更多种类效应蛋白的免疫受体奠定基础。
解析稻瘟病菌效应蛋白AvrPib的结构,分析其结构特征及其与植物受体识别的关键区域,阐明了效应蛋白躲避免疫受体识别的新机制(Plant J. 2018)。
2. 基于农药靶标的绿色农药筛选和设计
病原物在生长发育和致病过程中需要多种关键蛋白质的参与和调节。其中的部分蛋白质在植物,动物,和人体等非目标生物中不存在,是理想的新型农药的潜在靶标。解析这些靶标蛋白的结构和筛选特异性抑制剂及探究其调控过程的结构机制,不仅具有重要的理论意义,而且为基于结构设计和开发环境友好的高效杀菌剂提供坚实的基础。
解析稻瘟病菌的几丁质合成酶,6-磷酸海藻糖合成酶等潜在靶标蛋白的结构,分析其底物结合机制及底物结合位点,为以结构为基础的特异性化合物的设计提供思路。
筛选靶标蛋白的抑制剂,为绿色农药的研发提供前期基础。
3. 转录因子在植物抗病和病原物致病中发挥作用的结构机制
转录因子能够与顺式作用元件(cis-acting element) 发生特异性相互作用,从而对下游靶基因的表达起抑制或增强的作用。植物及其病原物中转录因子数量众多,在植物抗病以及病原物致病中发挥重要作用,其结合DNA序列的偏好性与其功能密切相关。其中WRKY转录因子是植物种重要的一类转录因子,在植物抗病过程中发挥重要的调节作用,阐释其识别DNA特异性的结构机理有利于从分子水平阐明水稻的抗病机制;同时,对稻瘟菌中转录因子调控致病的结构机制的研究将为深入分析稻瘟病菌以及其他病原真菌植病机理积累重要的素材,进而对稻瘟病等的防治具有指导意义。
解析了水稻WRKY45 DNA结合结构域与DNA复合物的结构,精确分析了WRKY识别W-box的分子机制尤其是水分子介导的氢键在识别中关键作用,建立了金属离子介导WRKY转录因子二体形成以结合DNA 的新模式(NAR2019)。
解析稻瘟病菌PCG2DNA结合结构域与核酸复合物的结构,分析其结构特征及其与核酸相互作用关键残基,验证了PCG2与核酸分子结合的模式(NAR2015)。
近期论文
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Discovery of novel isopropanolamine inhibitors against MoTPS1 as potential fungicides with unique mechanisms
Crystal structure of rice APIP6 reveals a new dimerization mode of RING-type E3 ligases that facilities the construction of its working model
A selective autophagy receptor VISP1 induces symptom recovery by targeting viral silencing suppressors
Structural mechanism of heavy metal-associated integrated domain engineering of paired nucleotide-binding and leucine-rich repeat proteins in rice
The tandem EH domains of End3 cooperate to interact with dual XPF motifs of Sla1 for the connection of early and late stages in fungal endocytosis
Structure-Aided Identification of an Inhibitor Targets Mps1 for the Management of Plant-Pathogenic Fungi
The rice blast fungus SR protein 1 regulates alternative splicing with unique mechanisms
Melatonin Functions as a Broad-spectrum Antifungal by Targeting a Conserved Pathogen Protein Kinase
The Receptor Binding Domain of SARS-CoV-2 Lambda Variant Has a Better Chance Than the Delta Variant in Evading BNT162b2 COVID-19 mRNA Vaccine-Induced Humoral Immunity
The Novel Protease Activities of JMJD5–JMJD6–JMJD7 and Arginine Methylation Activities of Arginine Methyltransferases Are Likely Coupled
Elucidation of ustilaginoidin biosynthesis reveals a previously unrecognised class of ene-reductases
A designer rice NLR immune receptor confers resistance to the rice blast fungus carrying noncorresponding avirulence effectors
Structure-guided Analysis of the Arabidopsis JASMONATE-INDUCED OXYGENASE (JOX) 2 Reveals Key Residues of Plant JOX Recognizing Jasmonic Acid Substrate
Up‐regulated 2‐alkenal reductase expression improves low‐nitrogen tolerance in maize by alleviating oxidative stress
Two distinct nucleic acid binding surfaces of Cdc5 regulate development
Crystal structures of Magnaporthe oryzae trehalose-6-phosphate synthase (MoTps1) suggest a model for catalytic process of Tps1
Structural basis of dimerization and dual W-box DNA recognition by rice WRKY domain
Crystal Structure of a Putative Modulator of Gyrase (TldE) from Thermococcus kodakarensis
The effect of phosphate ion on the ssDNA binding mode of MoSub1, a Sub1/PC4 homolog from rice blast fungus
Specific recognition of two MAX effectors by integrated HMA domains in plant immune receptors involves distinct binding surfaces
A positive charged patch and stabilized hydrophobic core are essential for avirulence function of AvrPib in the rice blast fungus
Crystallization of the rice immune receptor RGA5A_S with the rice blast fungus effector AVR1-CO39 prepared via mixture and tandem strategies
Structure based function-annotation of hypothetical protein MGG_01005 from Magnaporthe oryzae reveals it is the dynein light chain orthologue of dynlt1/3
Structures of complexes formed by H5 influenza hemagglutinin with a potent broadly neutralizing human monoclonal antibody
Substitution of tryptophan 89 with tyrosine switches the DNA binding mode of PC4
Expression, purification, crystallization and preliminary X-ray diffraction analysis of the effector-interaction domain of the resistance protein RGA5-A from Oryza sativa L. japonica
Structural basis of DNA recognition by PCG2 reveals a novel DNA binding mode for winged helix-turn-helix domains
Enhanced human receptor binding by H5 haemagglutinins
Changes in the hemagglutinin of H5N1 viruses during human infection – Influence on receptor binding
Receptor binding by a ferret-transmissible H5 avian influenza virus
Evolution of the receptor binding properties of the influenza A(H3N2) hemagglutinin
Structural features of the single-stranded DNA - Binding protein MoSub1 from Magnaporthe oryzae
H1N1 2009 Pandemic Influenza Virus: Resistance of the I223R Neuraminidase Mutant Explained by Kinetic and Structural Analysis
Seeding' with protease to optimize protein crystallization conditions in in situ proteolysis
Structures of receptor complexes formed by hemagglutinins from the Asian Influenza pandemic of 1957
Structural basis for oseltamivir resistance of influenza viruses
Crystal structures of oseltamivir-resistant influenza virus neuraminidase mutants
cDNA cloning and expression of earthworm fibrinolytic enzyme component A