研究领域
一个蛋白质在细胞内的生命轨迹就如同人的一生,从“出生”(合成)到“死亡”(降解),会在不同的时间去到不同的地方(时空定位),遇到很多的“人和事” (相互作用),并承担着自己的“社会责任” (功能执行)。秦为课题组长期的研究目标是系统解析蛋白质组在时间,空间,相互作用和功能等多个维度中的动态调控。本课题组将广泛地结合化学生物学和基于质谱的蛋白质组学,围绕蛋白质动态调控,生物大分子相互作用,翻译后修饰等重要生物学问题,进一步发展功能驱动的,具有时空动态分辨率的的新型化学蛋白质组学技术。具体研究大方向如下:
1. 发展新型化学蛋白质组学技术研究蛋白质的时空调控机制
蛋白质的功能在时间和空间等多个维度上发生着动态变化,发展多维度的蛋白质组学方法可以系统解析细胞内不同蛋白质的生命轨迹。本课题组将发展和利用不同的化学生物学工具探索蛋白质组的时空动态信息,例如发展新型邻近标记技术TransitID解析蛋白质在空间上的动态转运(Qin W., et al. Cell. 2023); 以及利用代谢标记探针定量分析蛋白质的合成与降解速率 (Qin W., et al. PNAS. 2017).
2. 发展新型化学蛋白质组学策略研究蛋白与生物分子间的相互作用
蛋白质与各种生物分子间存在着广泛的相互作用,包括蛋白-核酸相互作用,蛋白-蛋白相互作用,蛋白-代谢物相互作用等。这些相互作用经常是瞬时且动态的,但却往往影响着彼此的功能。本课题组将发展一系列高灵敏度和高特异性的邻近标记技术捕捉蛋白质与各种生物分子间的相互作用,并将其应用于解析宿主病原体相互界面中的潜在调控机制。(Qin W., et al. Nat. Commun. 2021.; Qin W., et al. Nat. Methods. 2021. Qin W., et al. Curr. Opin. Chem. Biol. 2019.)
3. 探索宿主与病原体相互作用界面中的功能性翻译后修饰
在宿主和病原体的相互作用界面中,存在着很多种类的蛋白翻译后修饰。例如,病原体释放的一些效应蛋白可以催化产生一些在宿主蛋白上非常独特的翻译后修饰,而宿主细胞也可以通过调控自身翻译后修饰的水平参与到免疫响应中。本课题组将致力于发展新型化学蛋白质组学方法用于挖掘宿主与病原体相互作用界面中的功能性翻译后修饰,包括衣康酸修饰和O-GlcNAc修饰,甚至是探索全新形式的翻译后修饰。(Qin W., et al. Nat. Chem. Biol. 2019. Qin W., et al. J. Am. Chem. Soc. 2020; Qin W., et al. Angew. Chem. Int. Ed. 2018; Liu J., et al. Cell. Chem. Biol. 2021. Qin W., et al. Biochemistry. 2019.)
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Qin, W. #; Cheah, JS. #; Xu, C.; Messing, J.; Freibaum, BD.; Boeynaems, S.; Taylor, JP.; Udeshi, ND.; Carr, SA.; Ting, AY*. Dynamic mapping of proteome trafficking within and between living cells by TransitID. Cell . 2023.(#EqualContribution) https://pubmed.ncbi.nlm.nih.gov/36798302/
Qin, W.; Samuel, MA.; Carey, CK.; Carr, SA.; Ting, AY*., Spatiotemporally-resolved mapping of RNA binding proteins via functional proximity labeling reveals a mitochondrial mRNA anchor promoting stress recovery. Nat. Commun. 2021. https://pubmed.ncbi.nlm.nih.gov/34404792/
Qin, W. #; Cho, FK. #; Cavanagh, PE. #; Ting AY*., Deciphering Molecular Interactions by Proximity Labeling. Nat. Methods. 2021. (# EqualContribution) https://pubmed.ncbi.nlm.nih.gov/33432242/
Liu, J. #; Shao, X. #; Qin, W.#; Zhang, Y. #; Dang, F.; Yang, Q.; Yu, X.; Li, YX.; Chen, X.*; Wang, C.*; Wang, YL.*, Quantitative Chemoproteomics Reveals O-GlcNAcylation of Cystathionine γ-lyase Represses Trophoblast Syncytialization. Cell Chem. Biol. 2021. (# EqualContribution) (Selected as cover) https://pubmed.ncbi.nlm.nih.gov/33626323/
Qin, W.#; Zhang, Y.#; Tang, H.; Liu D.; Chen, Y.; Liu, Y.; Wang, C.*, Chemoproteomic Profiling of Itaconation by Bioorthogonal Probes in Inflammatory Macrophages. J. Am. Chem. Soc. 2020. (# EqualContribution) https://pubmed.ncbi.nlm.nih.gov/32496768/
Qin, W.; Qin, K.; Zhang, Y.; Jia, W.; Chen, Y.; Cheng, B.; Peng, L.; Chen, N.; Liu, Y.; Zhou, W.; Wang, YL.; Chen, X.*; Wang, C.*, S-glycosylation-based cysteine profiling reveals regulation of glycolysis by itaconate. Nat. Chem. Biol. 2019, 15 (10), 983-991. https://pubmed.ncbi.nlm.nih.gov/31332308/
Qin, W.#; Qin, K.#; Fan, X.; Peng, L.; Hong, W.; Zhu, Y.; Lv, P.; Du, Y.; Huang, R.; Han, M.; Cheng, B.; Liu, Y.; Zhou, W.; Wang, C.*; Chen, X.*, Artificial Cysteine S-Glycosylation Induced by Per-O-Acetylated Unnatural Monosaccharides during Metabolic Glycan Labeling. Angew. Chem. Int. Ed. 2018, 57 (7), 1817-1820. (# EqualContribution) (Selected as back cover and very important paper) https://pubmed.ncbi.nlm.nih.gov/29237092/
Qin, W.; Lv, P.; Fan, X.; Quan, B.; Zhu, Y.; Qin, K.; Chen, Y.; Wang, C.*; Chen, X.*, Quantitative Time-resolved Chemoproteomics Reveals that Stable O-GlcNAc Regulates Box C/D snoRNP Biogenesis. Proc. Natl. Acad. Sci. USA 2017, 114 (33), E6749-e6758. https://pubmed.ncbi.nlm.nih.gov/28760965/
Qin, W.; Xie, Z.; Wang, J.; Peng, L; Ou, G.; Wang, C.*; Chen, X.*, Chemoproteomic Profiling of Protein O-GlcNAcylation in Caenorhabditis Elegans. Biochemistry 2019, doi: 10.1021/acs.biochem.9b00622. https://pubmed.ncbi.nlm.nih.gov/31682414/
Qin, W.; Yang, F.; Wang, C.*, Chemoproteomic Profiling of Protein-Metabolite Interactions. Curr. Opin. Chem. Biol. 2019, 54, 28-36. https://pubmed.ncbi.nlm.nih.gov/31812894/
Zhang, Y.; Qin, W.; Liu D.; Liu, Y.; Wang, C.*, Chemoproteomic profiling of itaconations in Salmonella. Chem. Sci. 2021. https://pubmed.ncbi.nlm.nih.gov/33996001/
Zhang, Y.; Qin, W.; Wang, C.*, Discovery of post-translational modifications in immunometabolism by chemical proteomics. Curr. Opin. Biotech. 2021, 68, 1-7. https://pubmed.ncbi.nlm.nih.gov/33113497/
Hao, Y.#; Fan, X.#; Shi, Y.; Zhang, C.; Sun, DE.; Qin, K.; Qin, W.; Zhou, W.; Chen, X.*, Next-generation Unnatural Monosaccharides Reveal that ESRRB O-GlcNAcylation Regulates Pluripotency of Mouse Embryonic Stem Cells. Nat. Commun. 2019, 10 (1), 4065. (# EqualContribution) https://pubmed.ncbi.nlm.nih.gov/31492838/
Qin, K.#; Zhu, Y.#; Qin, W.; Gao, J.; Shao, X.; Wang, Y.; Zhou, W.*; Wang, C.*;. Chen, X.*, Quantitative Profiling of Protein O-GlcNAcylation Sites by an Isotope-Tagged Cleavable Linker. ACS Chem. Biol. 2018, 13(8),1983-1989. (# EqualContribution) https://pubmed.ncbi.nlm.nih.gov/30059200/
Chen, Y.; Liu, Y.; Lan, T.; Qin, W.; Zhu, Y.; Qin, K.; Gao, J.; Wang, H.; Hou, X.; Chen, N.; Friedmann Angeli JP.; Conrad M.; Wang, C.*, Quantitative Profiling of Protein Carbonylations in Ferroptosis by an Aniline-Derived Probe. J. Am. Chem. Soc. 2018, 140, 4712-4720. https://pubmed.ncbi.nlm.nih.gov/29569437/
Chen, Y.; Qin, W.; Wang, C.*, Chemoproteomic Profiling of Protein Modifications by Lipid-derived Electrophiles. Curr. Opin. Chem. Biol.2016, 30, 37-45. https://pubmed.ncbi.nlm.nih.gov/26625013/
Liu, Y.; Liu, K.; Qin, W.; Liu, C.; Zheng, X.; Deng, Y.; Qing, H.*, Effects of Stem Cell Therapy on Protein Profile of Parkinsonian Rats Using an 18 O-labeling Quantitative Proteomic Approach. Proteomics2016, 16 (6), 1023-32. https://pubmed.ncbi.nlm.nih.gov/26791447/