研究方向、承担课题及发表论文概述 本课题组研究方向为分子生物学,主要研究领域为利用基因组学、分子生物学、分析化学、生物信息学等手段,围绕DNA和RNA等生物大分子上的表观遗传修饰的发现、检测、功能鉴定、生物合成途径,以及DNA损伤/修复的分子机理等方向进行研究。 承担课题: 1. 国家自然科学基金面上项目,32070629,tRNA片段及RNA磷硫酰化修饰在细胞应激反应中的动态变化规律研究,2021.01-2024.12,在研,主持 2. 美国自然科学基金(NSF),1709364, Chemical and biochemical determinants of phosphorothioate stability and location in bacterial genomes, 2017.8.1-2020.7.31,350万元,已结题,参加 3. 国家自然科学基金青年项目,31400029,沙门氏菌DNA磷硫酰化修饰蛋白复合物的功能研究,2015.01-2017.12,24万元,已结题,参加 4. 国家自然科学基金面上项目,31470183,细菌基因组上DNA磷硫酰化修饰的丰度和序列特异性,2015.01-2018.12,88万元,已结题,参加 5. 美国国立健康研究院(NIH)重大研究计划,NIHRO1-ES024615,Translational Control of ROS Management,2014.08-2019.05,598万元,已结题,参加 6. 美国国家自然科学基金,MCB-1412379,Role of Nucleoside Modifications in tRNA Surveillance in Prokaryotes,2014.08-2017.07,100万元,已结题,参加 7. 国家重点基础研究发展计划(973计划),2012CB721004,DNA硫修饰依赖限制系统的功能分析,2012.01-2013.12,60万元,已结题,参加 科研论文: 1. Hu J, Yim D, Ma D, Huber MS, Davis N, Bacusmo JM, Vermeulen S, Zhou J, Begley TJ, DeMott MS, Levine SS, Crécy-Lagard V, Dedon PC*, Cao B*. Sequencing-based quantitative mapping of the cellular small RNA landscape. 2020, BioRxive doi: https://doi.org/10.1101/841130 (under review at Nature Biotechnology) 2. Cao B, Yuan Y, Byrne S, Haruehanroengra P, Wu J, DeMott MS, Dedon PC*. Chemistry at the genomic level: Sequencing tools to define the chemical landscape of epigenetics, epitranscriptomics, and DNA damage. 2020, (invited review article by Accounts of Chemical Research). 3. Wu X#, Cao B#, Aquino P, Chiu TP, Chen C, Jiang S, Deng Z, Chen S, Rohs R, Wang L, Galagan JE, Dedon PC. Epigenetic competition reveals density-dependent regulation and target site plasticity of phosphorothioate epigenetics in bacteria. Proc NatlAcad Sci USA. 2020Jun 23;117(25):14322-14330. doi: 10.1073/pnas.2002933117. 4. Cao B*#, Wu X#, Zhou J, Wu H, Liu L, Zhang Q, DeMott MS, Gu C, Wang L, You D, Dedon PC*. Nick-seq for single-nucleotide resolution genomic maps of DNA modifications and damage. Nucleic Acid Research. 2020 Jul 9;48(12):6715-6725. doi: 10.1093/nar/gkaa473. 5. Lutz T, Czapinska H, Fomenkov A, Potapov V, Heiter DF, Cao B, Dedon P, Bochtler M, Xu SY*. Protein Domain Guided Screen for Sequence Specific and Phosphorothioate-Dependent Restriction Endonucleases. Front Microbiol. 2020 Aug 18;11:1960. doi: 10.3389/fmicb. 6. Sun Y, Kong L, Wu G, Cao B, Pang X, Deng Z, Dedon PC, Zhang C, You D*. DNA Phosphorothioate Modifications Are Widely Distributed in the Human Microbiome.Biomolecules. 2020 Aug 12;10(8):1175. 7. Zhu S, Zheng T, Kong L, Li J, Cao B, DeMott MS, Sun Y, Chen Y, Deng Z, Dedon PC, You D*. Development of Methods Derived from Iodine-Induced Specific Cleavage for Identification and Quantitation of DNA Phosphorothioate Modifications. Biomolecules 2020, 10(11), 1491. 8. Kellner SM, DeMott MS, Cheng C, Russell B, Cao B, Dedon PC*. Oxidation of labile phosphorothioate DNA modifications leads to lethal genomic instability. Nat Chem Biol. 2017 Aug;13(8):888-894. 9. Zheng X; Cheng Q; Yao F; Wang X; Kong L; Cao B; Xu M; Lin S; Chooi YH; You D*. Biosynthesis of the pyrrolidine protein synthesis inhibitor anisomycin involves novel gene ensemble and cryptic biosynthetic steps, Proc Natl Acad Sci U S A., 2017.4.18, 114(16): 4135~4140 10. Kong L, Zhang W, Chooi YH, Wang L, Cao B, Deng Z, Chu Y, You D*. A Multifunctional Monooxygenase XanO4 Catalyzes Xanthone Formation in Xantholipin Biosynthesis via a Cryptic Demethoxylation. Cell Chem Biol. 2016, 23(4):508-16. 11. Zheng T, Jiang P, Cao B, Cheng Q, Kong L, Zheng X, Hu Q, You D*. DndEi Exhibits Helicase Activity Essential for DNA Phosphorothioate Modification and ATPase Activity Strongly Stimulated by DNA Substrate with a GAAC/GTTC Motif. J Biol Chem. 2016, 291 (3), 1492-500. 12. Cao B, Zheng X, Cheng Q, Yao F, Zheng T, Ramesh Babu I, Zhou H, Dedon PC, You D*. In vitro analysis of phosphorothioate modification of DNA reveals substrate recognition by a multiprotein complex. Sci Rep. 2015, 5, 12513. 13. Cheng Q#, Cao B#, Yao F, Li J, Deng Z, You D*. Regulation of DNA phosphorothioate modifications by the transcriptional regulator DptB in Salmonella. Mol Microbiol. 2015, 97 (6), 1186-94. 14. Cao B#, Chen C#, DeMott MS#, Cheng Q, Clark TA, Xiong X, Zheng X, Butty V, Levine SS, Yuan G, Boitano M, Luong K, Song Y, Zhou X, Deng Z, Turner SW, Korlach J, You D*, Wang L*, Chen S*, Dedon PC. Genomic mapping of phosphorothioates reveals partial modification of short consensus sequences. Nat Commun. 2014, 5, 3951. 15. Cao B, Cheng Q, Gu C, Yao F, DeMott MS, Zheng X, Deng Z, Dedon PC*, You D*. Pathological phenotypes and in vivo DNA cleavage by unrestrained activity of a phosphorothioate-based restriction system in Salmonella. Mol Microbiol. 2014, 93 (4), 776-85. 16. Cao B, Yao F, Zheng X, Cui D, Shao Y, Zhu C, Deng Z, You D*. Genome mining of the biosynthetic gene cluster of the polyene macrolide antibiotic tetramycin and characterization of a P450 monooxygenase involved in the hydroxylation of the tetramycin B polyol segment. Chembiochem. 2012, 13 (15), 2234-42. 专利技术 1. 曹博,一种定位基因组DNA上损伤和修饰位点的方法,2019.8.9,中国专利,授权号:ZL 201811145591.6 2. 曹博,一种对RNA分子进行绝对定量的高通量测序方法,2019.7.9,中国专利,授权号:ZL 201811145601.6 3. 曹博,张清华,刘莉莉,季红,一种DNA 可逆保护和分离的方法,2020.6.11,中国专利,申请号: 202010528082.2 4. Bo Cao; Peter C. Dedon; Jennifer F. Hu; Michael S. DeMott, METHODS OF QUANTIFYING RNA AND DNA VARIANTS THROUGH SEQUENCING EMPLOYING PHOSPHOROTHIOATES, 2018.3.15, 美国专利,授权号:M0656.70437US00,国际专利,授权号:PCT/US2019/013714。 5. Peter C. Dedon; Delin You; Bo Cao; Ramesh Babu Indrakanti; Michael S. DeMott; Lianrong Wang; Zixin Deng; Xiufen Zhou, Enzymatic phosphorothioation of DNA or RNA, 2014.10.16, 美国专利,授权号: US20140308711A1, 国际专利,授权号: PCT/US2014/026241。 6. 由德林; 曹博; 邓子新; 郑晓青, 磷硫酰化DNA酶促合成方法, 2014.12.10, 中国专利,授权号: ZL 2012 1 0091733.1 |