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威尼人登录网址:付新苗 研究员

时间:2019-09-04浏览:12117

Principal Investigator:

Xinmiao Fu (付新苗), Ph.D.

Professor of Biochemistry and Molecular Biology

Vice Dean, College of Life Sciences, Fujian Normal University

Director of Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation

Director of Core Facilities and Services, College of Life Sciences

Address: Ligong Building, Room 214, Fujian Normal University (Qishan Campus), Fuzhou City, Fujian Province 350117, China

Email:xmfu(at)fjnu dot edu dot cn


Xinmiao Fu, born in Yueyang City, Hunan Province, received his BS in Environmental Engineering in 2000 and earned his PhD in Biology in 2004, both at Tsinghua University. He was a postdoctoral fellow first at UC Riverside with Jian-Kang Zhu, who is a famous plant biologist honored as a member of the US National Academy of Sciences, and later at the University of Kansas Medical Center with Professor Bao-Ting Zhu. He joined the faculty of Peking University (School of Life Sciences) in 2010, and moved to Fujian Normal University and became a full professor of biochemistry and molecular biology in 2016.


Fu’s research is focused on the molecular mechanisms underlying antibiotic resistance, persister formation and stress response in bacterial pathogens. His research group has used genomic library screen, random mutagenesis, molecular biology, protein purification, genome sequencing, RNA-seq and so on to study these mechanisms. His long-term goal is to develop new antibacterial peptides and antibiotic potentiation strategies for combatting antibiotic-resistant/tolerant pathogens. In addition, Prof. Fu is also interested in the epidemiology of infectious diseases. Recently, he and his colleagues developed a series of approaches for simulating and forecasting the trend and course of the COVID-19 outbreaks in China and worldwide.


Publications

2016-present (at Fujian Normal University)

1. Gao, Y.*, Chen, Z., Yao, W., Li, D., Fu, X*. Gentamicin combined with hypoionic shock rapidly eradicates aquaculture bacteria in vitro and in vivo,Frontiers in Microbiology (2021), accepted, https://www.frontiersin.org/articles/10.3389/fmicb.2021.641846/

2. Yang Liu#, Jiayu Yu#, Mengyuan Wang#, Qingfang Zeng, Xinmiao Fu, Zengyi Chang*, A high-throughput genetically directed protein crosslinking analysis reveals the physiological relevance of the ATP synthase 'inserted' state, FEBS J 2020 Oct 31. doi: 10.1111/febs.15616.

3. Fengqi Sun , Mengmeng Bian , Zhongyan Li, Boyan LV , Yuanyuan Gao , Yan Wang* and Xinmiao Fu*. 5-Methylindole Potentiates Aminoglycoside against Gram-positive Bacteria Including Staphylococcus aureus Persisters under Hypoionic Conditions. Front Cell Infect Microbiol (2020), Feb 28;10:84 doi: 10.3389/fcimb.2020.00084

4. Yanna Zhao, Boyan Lv, Fengqi Sun, Jiafeng Liu, Yan Wang, Yuanyuan Gao, Feng Qi, Zengyi Chang* and Xinmiao Fu*. Rapid Freezing Enables Aminoglycosides to Eradicate Bacterial Persisters via Enhancing Mechanosensitive Channel MscL-mediated Antibiotic Uptake. mBio(2020) 11(1): e03239-19. https://doi.org/10.1128/mBio.03239-19.

5. Shuang Zhang, Yu Cheng, Jing Ma, Yan Wang, Zengyi Chang*, Xinmiao Fu*. DegP degrades a wide range of substrate proteins in Escherichia coli under stress conditions. Biochemical Journal (2019), 476 3549–3564, https://doi.org/10.1042/BCJ20190446

6. Zhongyu Chen, Yuanyuan Gao*, Boyan Lv, Yan Wang and Xinmiao Fu*, Hypoionic shock facilitates aminoglycoside killing of both nutrient shift- and starvation-induced bacterial persister cells by rapidly enhancing aminoglycoside uptake. Frontiers in Microbiology (2019) Sep 6, 10: 2028. doi: 10.3389/fmicb.2019.02028

7. Cheng Long, Xin-Miao Fu, Zhi-Fu Fu*, Global analysis of daily new COVID-19 cases reveals many static-phase countries including the United States potentially with unstoppable epidemic. World J Clin Cases 2020 October 6; 8(19): 0-0 DOI: 10.12998/wjcc.v8.i19.0000

8. Yuanyuan Gao #, Zuqin Zhang #, Wei Yao, Qi Ying, Cheng Long * and Xinmiao Fu*. Forecasting the Cumulative Number of COVID-19 Deaths in China: a Boltzmann Function-based Modeling Study, Infection Control & Hospital Epidemiology (2020), http://dx.doi.org/10.1017/ice.2020.101.(In this study, we accurately estimated the total number of COVID-19 deaths in China, Hubei and Wuhan by applying a novel approach)

9. Boyan Lv #, Zhongyan Li #, Yajuan Chen , Cheng Long * and Xinmiao Fu *. Global COVID-19 fatality analysis reveals Hubei-like countries potentially with severe outbreaks, Journal of Infection (2020), https://doi.org/10.1016/j.jinf.2020.03.029(This study indicates that Italy and USA are similar to Hubei, China in the severity of COVID-19 epidemic)

10. Kedong Zhao #, Cheng Long #, Yan Wang *, Tieyong Zeng and Xinmiao Fu *. Negligible Risk of the COVID-19 Resurgence Caused by Work Resuming in China (outside Hubei): a Statistical Probability Study, Journal of Public Health (2020), https://doi.org/10.1093/pubmed/fdaa046.

11. Zuqin Zhang #, Wei Yao #, Yan Wang, Cheng Long * and Xinmiao Fu *. Wuhan and Hubei COVID-19 mortality analysis reveals the critical role of timely supply of medical resources, Journal of Infection (2020), https://doi.org/10.1016/j.jinf.2020.03.018(This study indicates that timely supplied hospital beds and health workers are critical for life-saving in Hubei and Wuhan when COVID-19 patients overwhelm the health care system)

12. Xinmiao Fu*, Qi Ying, Tieyong Zeng, Tao Long, Yan Wang. Simulating and Forecasting the Cumulative Confirmed Cases of SARS-CoV-2 in China by Boltzmann Function-based Regression Analyses, Journal of Infection (2020), https://doi.org/10.1016/j.jinf.2020.02.019 (In this study, we accurately estimated the total number of COVID-19 infections in China, Hubei and Wuhan by applying a novel approach, and also precisely predicted the date when the COVID-19 crisis will end in China). 

13. Fu X, Chang Z, Biogenesis, quality control, and structural dynamics of proteins as explored in living cells via site-directed photocrosslinking. Protein Science 2019 Jul; 28(7):1194-1209 doi: 10.1002/pro.3627.

14. Fu X#, *, Wang Y#, Song X, Shi X, Shao H, Liu Y, Zhang M, Chang Z*. Subunit interactions as mediated by "non-interface" residues in living cells for multiple homo-oligomeric proteins.Biochem Biophys Res Commun(2019) Apr 23;512(1):100-105. doi: 10.1016/j.bbrc.2019.03.004. 

15. Fu X #, *, Wang Y#, Shao H, Ma J, Song X, Zhang M, Chang Z*. DegP functions as a critical protease for bacterial acid resistance. FEBS Journal  (2018), 285: 3525–3538.

16. Long C, Lv G, Fu X *. Development of a general logistic model for disease risk prediction using multiple SNPs. FEBS Open Bio (2019), 9(11): 2006-2012.

2010-2016 (at Peking University)

17. Wang Y, Wang R, Jin F, Liu Y, Yu J, Fu X*, Chang Z*. A Supercomplex Spanning the Inner and Outer Membranes Mediates the Biogenesis of β-barrel Outer Membrane Proteins in Bacteria. J Biol Chem (2016), 291(32): 16720–16729.

18. Liu JF, Fu X*, and Chang Z*. A reciprocating motion-driven rotation mechanism for the ATP synthase, Science China Life Sciences, 2016, doi: 10.1007/s11427-015-4955-0.

19. Liu J,Fu X*, Chang Z*. Hypoionic shock treatment enables aminoglycosides antibiotics to eradicate bacterial persisters. Scientific Reports (2015), 5: 14247.

20. Zhang K, Ezemaduka AN, Wang Z, Hu H, Shi X, Liu C, Lu X, Fu X, Chang Z, Yin CC. A novel mechanism for small heat shock proteins to function as molecular chaperones. Scientific Reports, 2015, 5: 8811

21. Fu X, Tang Y, Dickinson BC, Chang CJ, Chang Z. An oxidative fluctuation hypothesis of aging generated by imaging H2O2 levels in live Caenorhabditis elegans with altered lifespans. Biochem Biophys Res Commun,2015, 458(4):896-900.

22. Zou Z, 31. Fu X*. Abiotic regulation: a common way for proteins to modulate their functions. Curr Protein Pept Sci(2015), 16(3):188-95. (editor-invited review)

23. Fu X*, Chang Z, Shi X, Bu D, Wang C. Multilevel structural characteristics for the natural substrate proteins of bacterial small heat shock proteins. Protein Sci, 2014 , 23: 229-237

24. Shi X, Yan L, Zhang H, Sun K, Chang Z, Fu X*. Differential degradation for small heat shock proteins IbpA and IbpB is synchronized in Escherichia coli: implications for their functional cooperation in substrate refolding. Biochem Biophys Res Commun, 2014, 452(3):402-7

25. Ezemaduka A, Yu J, Shi X, Zhang K, Yin C, Fu X*, Chang Z*. A small heat shock protein enables Escherichia coli to grow at a lethal temperature of 50?C conceivably by maintaining cell envelope integrity. Journal of Bacteriology (2014) 196:2004-2011

26. Ge X, Lyu ZX, Liu Y, Wang R, Zhao XS, Fu X*, Chang Z*. Identification of FkpA as a key quality control factor for the biogenesis of outer membrane proteins under heat shock conditions.Journal of Bacteriology (2014), 196: 672-680

27. Fu X*. Chaperone function and mechanism of small heat shock proteins. Acta Biochimica et Biophysica Sinica (2014), 46(5):347-56 (editor-invited review)

27. Ge X, Wang R, Ma J, Liu Y, Ezemaduka A, Chen P, Fu X* and Chang Z*. DegP primarily functions as a protease for the biogenesis of β-barrel outer membrane proteins in Gram-negative bacterium Escherichia coli.FEBS Journal  (2014), 281: 1226-1240

28. Fu X*, Shi X, Yan L, Zhang H, Chang Z*. In vivo substrate diversity and preference of small heat shock protein IbpB as revealed by using a genetically incorporated photo-crosslinker.J Biol Chem (2013), 288(44):31646-54.

29. Fu X*, Shi X, Yin L, Liu J, Joo K, Lee J, Chang Z*. Small heat shock protein IbpB acts as a robust chaperone in living cells by hierarchically activating its multi-type substrate-binding residues.J Biol Chem (2013), 288(17):11897-906.

30. Hong W, Wu YE, Fu X, Chang Z. Chaperone-dependent mechanisms for acid resistance in enteric bacteria.Trends in Microbiology, 2012, Jul;20(7):328-35.

31. Zhang M, Lin S, Song X, Liu J, Fu Y, Ge X, Fu X, Chang Z, Chen PR. genetically incorporated crosslinker reveals chaperone cooperation in acid resistance.Nature Chemical Biology, 2011, 7: 671-677

32. Shi X, Wang Z, Yan L, Ezemaduka AN, Fan G, Wang R, Fu X, Yin CC, and Chang Z. Small heat shock protein AgsA forms dynamic fibrils. FEBS Letters, 2011, 585(21):3396-3402.

2005-2010 (in the US as a postdoc researcher)

33. Fu X, Wang P, Fukui M, Long C, Yin L, Choi HJ, Zhu BT. PDIp Is a Major Intracellular Estrogen-Storage Protein That Modulates the Tissue Levels of Estrogen in the Pancreas.Biochemical Journal (2012), 447(1):115-23.

34. Fu X and Zhu BT. Both PDI and PDIp can attack the native disulfide bonds in thermally-unfolded RNase and form stable disulfide-linked complexes.BBA-PROTEINS PROTEOM, 2011, 1814(4):487-95

35. Fu X, Wang P, Zhu BT. Characterization of the Estradiol-Binding Site Structure of Human Protein Disulfide Isomerase (PDI).PLoS ONE, 2011, 6(11):e27185.

36. Fu X, Wang P, Zhu BT. Characterization of the Estradiol-Binding Site Structure of Human Pancreas-Specific Protein Disulfide Isomerase: Indispensable Role of the Hydrogen Bond between His278 and the Estradiol 3-Hydroxyl Group.Biochemistry (2011), 50:106-115

37. Fu X, and Zhu BT. Human Pancreas-Specific Protein Disulfide Isomerase (PDIp) Can Function as a Chaperone Independently of Its Enzymatic Activity by Forming Stable Complexes with Denatured Substrate Proteins.Biochemical Journal (2010), 429:157-69

38. Fu X and Zhu BT. Human pancreas-specific protein disulfide isomerase homolog (PDIp) is an intracellular estrogen-binding protein that modulates estrogen levels and actions in target cells.J Steroid Biochem Mol Biol (2009), 115:20-29

39. Fu X, Dai X, Ding J, Zhu BT. Pancreas-specific protein disulfide isomerase has a cell type-specific expression in various mouse tissues and is absent in human pancreatic adenocarcinoma cells: implications for its functions.J Mol Histol., 2009, 40:189-99

40. Fu X and Zhu BT. Human pancreas-specific protein disulfide isomerase homolog (PDIp) is redox-regulated through formation of an inter-subunit disulfide bond.Arch Biochem Biophys, 2009, 485:1-9

41. Fu X, Wang P, Zhu BT. Protein disulfide isomerase is a multifunctional regulator of estrogenic status in target cells. J Steroid Biochem Mol Biol (2008), 112:127-37

42. Jiang XR, Wang P, Fu X and Zhu BT. Chemical synthesis and biochemical characterization of biotinylated derivatives of 17β-estradiol with a long side-chain covalently attached to its C-7α position. Steroids, 2008, 73:1252-61

43. Zhu J, Fu X, Koo YD, Zhu, JK, Jenney FEJr, Adams MW, Zhu Y, Shi H, Yun, DJ, Hasegawa PM and Bressan RA. An enhancer mutant of Arabidopsis salt overly sensitive 3 mediates both ion homeostasis and the oxidative stress response.Mol Cell Biol, 2007, 27:5214-5224.

44. Katiyar-Agarwal S, Zhu J, Kim K, Agarwal M, Fu X, Huang A and Zhu JK. The plasma membrane Na+/H+ antiporter SOS1 interacts with RCD1 and functions in oxidative stress tolerance in Arabidopsis.Proc Natl Acad Sci USA, 2006, 103:18816-18821

2000-2005 (at Tsinghua University and Peking University)

45. Fu X, Jiao W and Chang Z. Phylogenetic and biochemical studies reveal a potential evolutionary origin of animal small heat shock proteins from bacterial class A.J Mol Evol (2006), 62:257-266

46. Fu X and Chang Z. Identification of a Highly Conserved Pro-Gly Doublet in Non-animal Small Heat Shock Proteins and Characterization of Its Structural and Functional Roles in Mycobacterium tuberculosis Hsp16.3.Biochemistry (Moscow), 2006, 71 Suppl 1:S83-90

47. Feng Y, Jiao W, Fu X and Chang Z. Stepwise disassembly and apparent nonstepwise reassembly for the oligomeric RbsD protein. Protein Sci, 2006, 15:1441-1448

48. Fu X and Chang Z. Identification of bis-ANS binding sites in Mycobacterium tuberculosis small heat shock protein Hsp16.3: Evidences for a two-step substrate-binding mechanism.Biochem Biophys Res Commun, 2006, 349:167-171

49. Zhang H, Fu X and Chang Z. The association of small heat shock protein Hsp16.3 with the plasma membrane of Mycobacterium tuberculosis: dissociation of oligomers is a prerequisite.Biochem Biophy Res Commun, 2005, 330:1055-1061

50. Hong W, Jiao W, Hu J, Zhang J, Liu C, Fu X, Shen D, Xia B and Chang Z. Periplasmic protein HdeA exhibits chaperone-like activity exclusively within stomach pH range by transforming into disordered conformation.J Biol Chem, 2005, 280:27029-27034.

51. Fu X, Zhang H, Zhang X, Cao Y, Jiao W, Liu C, Song Y, Abulimiti A and Chang Z. A dual role for the N-terminal region of Mycobacterium tuberculosis Hsp16.3 in self-oligomerization and binding denaturing substrate proteins.J Biol Chem (2005), 280:6337-6348

52. Zhang X, Fu X, Zhang H and Chang Z. chaperone-like activity of beta-casein.Int J Biochem Cell Biol, 2005, 37:1232-1240.

53. Fu X, Zhang X and Chang Z. 4,4'-dianilino-1,1'-binaphthyl-5,5'-sulfonate (bis-ANS), a novel molecule having chaperone-like activity.Biochem Biophys Res Commun, 2005, 329:1087-1093.

54. Fu X, Jiao W, Abulimiti A and Chang Z. Inter-subunit cross-linking suppressed the dynamic oligomeric dissociation of Mycobacterium tuberculosis Hsp16.3 and reduced its chaperone activity.Biochemistry (Moscow), 2004, 69,552-557

55. Chen X, Fu X, Ma Y and Chang Z. Chaperone-like activity of Mycobacterium tuberculosis Hsp16.3 does not require its intact (native) structures. Biochemistry (Moscow), 2004, 70(8):913-9

56. Liu Y, Fu X, Shen J, Zhang H, Hong W and Chang Z. Periplasmic proteins of Escherichia coli are highly resistant to aggregation: revaluation for roles of molecular chaperones in periplasm.Biochem Biophy Res Commun,2004, 316:795-801.

57. Fu X and Chang Z. Temperature-dependent subunit exchange and chaperone-like activities of Hsp16.3, a small heat shock protein from Mycobacterium tuberculosis.Biochem Biophy Res Commun (2004), 316:291-299

58. Fu X, Li W, Mao Q and Chang Z. Disulfide bonds convert small heat shock protein Hsp16.3 from a chaperone to a non-chaperone: implications for the evolution of cysteine in molecular chaperones.Biochem Biophy Res Commun, 2003, 308: 627-635

59. Fu X, Liu C, Liu Y, Feng X, Gu L, Chen X and Chang Z. Small heat shock protein Hsp16.3 modulates its chaperone activity by adjusting the rate of oligomeric dissociation.Biochem Biophy Res Commun, 2003, 310: 412-420

60. Abulimiti A#, Fu X#, Gu L, Feng X and Chang Z. Mycobacterium tuberculosis Hsp16.3 Nonamers are Assembled and Re-assembled via Trimer and Hexamer Intermediates.J Mol Biol, 2003, 326:1013-1023, #contributed equally

61. Feng X, Huang S, Fu X, Abulimiti A and Chang Z. The reassembling process of the nonameric Mycobacterium tuberculosis small heat-shock protein Hsp16.3 occurs via a stepwise mechanism.Biochemical Journal, 2002, 363:329-334


Book Chapters

1. Fu X. Insights into how small heat shock proteins bind a great diversity of substrate proteins: a super-transformer model. In The Big Book on Small Heat Shock Protein World(ed. R.M. Tanguay and L.E. Hightower). Springer, 2015, p101-117.


专利:

1. 一种提高氨基糖类抗生素杀菌效率的新方法,付新苗,赵艳娜,孙凤琪,ZL201810074813.3,授权日2020218

2. 低离子休克提高氨基糖苷类抗生素杀灭持留菌效率的方法,付新苗,陈钟毓,高媛媛,ZL201811646368.X,授权日202091

3. 乙醇作为增敏剂提高氨基糖苷类抗生素杀菌效率的方法,付新苗,李中燕,张祖勤,高媛媛ZL 201811641533.2,授权日20201204

4. 高渗甘油预处理提高氨基糖苷类抗生素杀菌效率的方法,付新苗,卞蒙蒙,ZL201811433983.2,授权日20201215

5. 热休克提高氨基糖苷类抗生素杀灭革兰氏阴性菌的方法,付新苗,吕波燕,申请号:201810579703.2,授权日202138


Oral Presentations

1. 氨基糖苷类抗生素杀灭持留菌的“增效减毒”新方法:冰冻、吲哚和低离子休克的发现及其作用机理主旨报告,2020年中国微生物学会学术年会,20201023-26日,四川成都

2. Hypoionic shock facilitates aminoglycoside antibiotics killing of various bacterial persister cells by rapidly enhancing aminoglycoside uptake(分会场报告),2019年中国微生物学会学术年会,20191011-15日,山东济南

3. 低离子休克促进氨基糖苷类抗生素杀灭耐药菌的分子机制,福建省生物化学与分子生物学会2019年学术研讨会,20191123-24日,福建龙岩

4. Hypoionic shock facilitates aminoglycoside antibiotics killing of various bacterial persister cells by rapidly enhancing aminoglycoside uptake(分会报告),2019年中国微生物学会学术年会,20191011-15日,山东济南

5. 提高氨基糖苷类抗生素杀菌效率的新方法及其分子机理,华东六省一市生物化学与分子生物学学会2017年学术交流会,20171027-30日,安徽合肥

6. DegP acts as a critical protease for bacterial acid resistance, the Second Trilateral Workshop for Frontier Protein Studies, June 24-26, 2016, Osaka University, Osaka, Japan

7. Identification of substrate-binding sites and substrates of small heat shock protein by in vivo photo-crosslinking (分会报告). VIIth International Congress on Stress Response in Biology and Medicine, 2015916-19日,安徽黄山

8. Identification of substrate-binding sites and substrates of small heat shock protein by in vivo photo-crosslinking (分会报告)中国生物化学与分子生物学会第十一次会员代表大会暨2014年全国学术会议, 2014821-23日,福建厦门

9. In vivo substrate diversity and preference of small heat shock protein IbpB revealed by photo-crosslinkingYoung Scientist SessionThe 4th Asia Pacific Protein Association (the APPA2014 Conference),May 17-20, 2014, Jeju Island. South Korea

10. Chaperone function and mechanism of small heat shock proteins (青年科学家论坛). 第四届全国“跨学科蛋白质研究”学术讨论会,20131012-15日,安徽合肥

11. DegP帮助大肠杆菌抗热抗酸的分子机制 (邀请报告). 酶学和酶工程研讨班, 2013913-14日,四川,中科院成都生物所

12. DegP primarily functions as a protease for the biogenesis of outer membrane proteins in cells (邀请报告). Symposium on Protein Folding, Post-Translational Modification & Quality Control, 2013529日,北京中科院生物物理研究所

13. Defining the essential functions of DegP for the biogenesis of outer membrane proteins in cells (邀请报告). 第十一届全国酶学会议, 2013516-19. 江苏无锡

14. 蛋白质科学的前沿问题及研究展望 (邀请报告). 创新方法高层论坛,2010129日,中国北京.


中文版介绍

付新苗,研究员、博士生导师、威尼人登录网址副院长(分管科研), 细胞逆境响应与代谢调控福建省高校重点实验室主任,威尼人登录网址仪器设备共享平台(中心实验室)主任,Email:xmfu(at)fjnu.edu.cn, fuxinmiao(at)pku.edu.cn,威尼人登录网址旗山校区理工10号楼209/105

 

个人简介:1977年生,湖南岳阳人。2000年本科毕业于清华大学环境科学与工程系;2004年在清华大学生物科学与技术系获博士学位。从2005年到2010年,先后在美国加州大学河滨分校 (University of California Riverside)朱健康实验室和堪萨斯大学医学中心(University of Kansas Medical Center)朱宝亭实验室从事植物抗氧化和二硫键异构酶方面的研究。从201010月起,在北京大学威尼人登录网址工作,研究与膜蛋白生成质量控制相关的分子伴侣蛋白的作用机制,并拓展到细菌耐药领域。201610月正式加入威尼人登录网址,从事细菌耐药抗逆及耐药细菌杀灭策略方面的研究。

至今总计发表SCI 论文62篇,总引用次数超过 1900次,他引次数超过1400次,个人的H index23(Web of Science数据库中的引用次数计算)。通讯或共同通讯作者论文总计25篇,包括JBC、Journal of Infection3篇,Frontiers in Microbiology、Journal of Bacteriology、FEBS Journal2篇,mBio、Biochemical Journal、Scientific Reports、Front Cell Infect Microbiol、Infect Control Hosp Epidemiol等各1篇。授权5项发明专利,参与编写由Springer出版的专著。先后主持国家自然科学基金委青年项目和4项面上项目;参与1项国家973计划项目;参与国家自然基金委的《2011-2020年我国生物学学科发展战略》以及科技部的《“蛋白质研究”重大科学研究计划十三五实施方案(建议)》的编撰工作。获威尼人登录网址宝琛计划高端人才和福建省高校新世纪优秀人才支持计划等荣誉。实验室目前有副教授1人,讲师2人,博士研究生4人,硕士研究生12人,其中陈钟毓、张祖勤获国家奖学金。热忱欢迎有兴趣的学生报考硕士、博士研究生。


所获科研基金和人才项目资助

1.国家自然科学基金委(面上项目):大肠杆菌β桶外膜蛋白生成必需因子BamA的作用机制及其作为抗菌靶点的研究,31972918,2020.1-2023.12,58万,在研,主持

2.国家自然科学基金委(面上项目):线虫小分子热休克蛋白Hsp17/Hsp12s的生物学功能及其延长寿命的作用机制,31770830,2018.1-2021.12,60万,在研,主持

3.国家自然科学基金委(面上项目):大肠杆菌ATP合酶的旋转催化和活性调控机制,31570778,2016.1-2019.12,60万,结题,主持

4.国家自然科学基金委(面上项目):大肠杆菌分子伴侣蛋白HdeADegP协同抵抗酸胁迫的分子机制,31270804,2013.1-2016.12,78万,结题,主持

5.国家自然科学基金委(青年基金项目):折叠酶DsbA、DsbC、PDI在活细胞内和天然底物蛋白相互作用的分子机制,31100559,2012.1-2014.12,25万,结题,主持

6.教育部留学回国人员科研启动基金:折叠酶DsbA、DsbC、PDI在活细胞内和天然底物蛋白相互作用的分子机制,2013.1-2014.12,5万,结题,主持

7.国家重大科学研究计划(973计划):膜蛋白的生成、修饰、组装及质量控制,2012CB917300,2012.1-2016.12,100万,结题,学术骨干,首席科学家助理

8.国家自然科学基金委生命科学学部“十三五”学科发展战略报告(生物化学于分子生物学及生物物理学科),31440036,结题,参与编撰

9.科技部《“蛋白质研究”重大科学研究计划十三五实施方案(建议)》报告,参与编撰

  

10.2017年福建省引进高层次人才

11.2017年福建省高校新世纪优秀人才

12.2017年威尼人登录网址“宝琛计划”高端人才

13.2016年威尼人登录网址高层次人才建设经费


学术兼职:

福建省生物化学与分子生物学学会常务理事,《热带生物学报》、《World Journal of Clinical Cases》等杂志的编委

Cell Reports、Communications Biology、iScience、BBA-molecular cell research、Bioinformatics、ACS infectious diseases、Biochemistry (US)、Scientific Reports等杂志的审稿人


研究兴趣

1.细菌耐药的分子机制及其应用

细菌耐药正成为严重的临床医学问题,威胁动物和人类的健康,研究细菌耐药的机制、寻找有效杀菌的新方法具有重要的医学价值。本实验室从细菌休眠的角度研究细菌耐药的机理。休眠广泛的存在于细菌、植物、动物,例如熊和蛙的冬眠,结核杆菌在人体内的长期潜伏等。处于休眠状态的生物,代谢水平低,细胞停止生长分裂,抗逆能力增强,因此休眠是生物适应不利环境的重要策略。


处于休眠状态的细菌,抗逆能力显著增强,特别是对所有抗生素几乎都不响应,即抗生素耐受(antibiotic tolerance),这是目前诸多抗药细菌产生的根本原因。揭示细菌休眠的机理,包括怎样进入休眠、如何保持休眠、如何从休眠中苏醒等问题,既有基本的生物学意义,也具有重要的医学价值。本实验室以大肠杆菌为模型研究细菌休眠耐药的分子机理;在此基础上,利用适当的动物模型(大鼠、小鼠、斑马鱼等),以绿脓杆菌、金黄色葡萄球菌为对象,研究开发具有临床应用价值的杀菌新方法。这是我们的主要研究方向。


2.革兰氏阴性细菌外膜蛋白生成的机制及其在抗菌药物开发中的应用

任何生物在其生命过程中都不可避免地要面临各种各样的胁迫(stress conditions,如极端的温度和酸碱度、干旱等等)。环境胁迫会诱导细胞内产生一大类具有保护功能的热休克蛋白(heat shock proteins,也被称为“分子伴侣蛋白”或“胁迫蛋白”)。分子伴侣蛋白对细胞内的其它蛋白质进行广义的“质量控制”(quality control),在蛋白质的“生、老、病、死”过程中发挥重要作用。研究分子伴侣蛋白的生物学功能及蛋白质质量控制的机制既有基本的生物学意义,也具有一定的应用价值,例如作为药物设计的靶标。


本实验室关注和细菌膜蛋白生成有关的质量控制因子,例如参与外膜蛋白生成的因子SurA、Skp、FkpA、DegP、SecYEG、BamA等。主要借助活细胞非天然氨基酸光交联、化学交联等技术手段,研究这些蛋白因子的生物学功能和作用机制,在此基础上,发展新的抗菌药物。由于这些靶标蛋白都位于细胞外套(外膜、膜间质、内膜外侧等),因此药物极易和靶标结合,不存在摄取效率低和药物外排的问题。和目前广泛使用的抗生素(其靶标通常是细胞质蛋白)相比,这类新型抗生素具有一定优势,发展潜力巨大。


3. 传统抗生素的增效减毒研究

开发新型抗生素固然是应对细菌耐药的重要策略,但其难度和风险巨大。事实上,自上世纪90年代至今,全世界并没有新型结构类型的抗生素投入临床使用。另一方面,诸多传统抗生素仍然具有巨大的价值,但受制于耐药性和毒副作用而不能发挥应有的效果。因此,针对这些抗生素的增效(增强杀菌效果)减毒(减少毒副作用)研究具有重要的意义。

本实验室以氨基糖糖苷类抗生素为重点,发展了多种增效减毒的方法,包括物理增强方法(如低离子休克、快速冰冻)和化学增敏剂等。这些方法能将不同类型的氨基糖苷类抗生素(如庆大霉素、卡那霉素、链霉素)的杀菌效率提高百倍到百万倍不等,同时,其药物暴露时间可以降低到一分钟。深入揭示其背后的分子机制,将为开发出应用于临床和动物疾病防治的方法提供重要参考。

 

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