駱觀正,男,博士,中山大學生命科學學院教授、博士生導師。
基本介紹
- 中文名:駱觀正
- 畢業院校:中科院遺傳發育所
- 學位/學歷:博士
- 專業方向:生物信息學
- 任職院校:中山大學
研究方向,個人經歷,講授課程,學術成就,承擔課題,論文專著,
研究方向
從達爾文到孟德爾和摩爾根,生命科學的先驅在漫漫長夜中艱難前行。直到中心法則的確立,生命科學才迎來了真正的曙光。近年來,在以二代測序和基因編輯為代表的新技術的推動下,生命科學的發展迎來了黃金時代,也對越來越多的人產生了深遠的影響。人類健康,地球生態,我們的衣食住行,包括能源、環境,生命科學已成為當今的核心科學,而在可預見的將來,還會持續性的增強對整個人類社會的影響力。
在一片欣欣向榮的景象下,生命的終極奧秘似乎唾手可得。獲得一個人類基因組的信息,只需要普通實驗室數天的時間。然而這時候,我們才“知道自己不知道”。基因組從獲取到解析,還有著無數的問題等待解答。我們實驗室也將致力於發展新的分子工具和分析手段,以表觀遺傳作為切入點,為基因組的最終解碼(decode)貢獻一份力量。另一方面,有限的認知並不能阻擋人類改變世界的欲望。我們也將把解碼的成果嘗試套用到再編碼(encode)上,從工程生物學的角度,來探索研究成果的實際套用潛力。
實驗室經過兩年時間的發展,各方麵條件已初步完善,課題進展順利,已有學生和博後有第一作者文章發表。目前實驗室固定成員包括9名學生和2名博士後。實驗室研究興趣廣泛,鼓勵創新,歡迎對探索生命本質有著強烈興趣的同學加入。
個人經歷
2019-至今,獲“優秀青年”基金資助
2018-至今,獲聘“青年珠江學者”
2017-至今,中山大學生命科學學院,教授
2013-2017,芝加哥大學,生物分子動態研究所,博士後(合作導師:何川)
2010-2013,中科院遺傳發育所,分子系統中心,助理研究員
2005-2010,中科院遺傳發育所,生物信息學,理學博士 (導師:王秀傑)
2001-2005,東南大學,生物醫學工程,工程學士
講授課程
分子生物學(主講,2019-)
現代生命科學進展(參與,2019)
基因組時代的進化與計算生物學(參與,2018)
專業科技文獻閱讀和理解(參與,2018)
醫療新時代:精準個性化醫療(主講,2017-2018)
學術成就
隨著人類基因組計畫的完成和測序技術的發展,我們獲得生物數據的能力得到革命性的提升,而如何解析和利用這些數據,成為了當今生命科學領域的焦點。基因之間的互作及調控規律是最基礎的問題之一,研究基因調控對我們理解生長發育、遺傳變異、生理生態,乃至人類疾病,都有著極為重要的意義。基因調控大致可以分為轉錄前和轉錄後兩個層面。轉錄前調控的決定因素之一是DNA修飾。之前的研究基本集中在5位甲基胞嘧啶上(5mC),對其它修飾類型的研究還非常稀缺。轉錄後調控則更加複雜,其中關於非編碼RNA介導的基因沉默已得到深入的研究,而編碼基因本身是否受到修飾的調控是目前研究的焦點。課題組長期以來對基因的調控規律有著濃厚的興趣,特別是圍繞著新型DNA和RNA修飾介導的基因調控模式開展了持續性的研究。在轉錄前調控方面,開發出針對DNAN6甲基腺嘌呤(6mA)修飾的高通量測序方法,並首次揭示了真核生物中6mA的全基因組分布圖譜,發現6mA和染色質的互作規律及對基因轉錄的調控功能。在轉錄後調控方面,發現以m6A為代表的RNA修飾是調節基因表達的重要途徑之一,並通過發展單鹼基解析度檢測技術m6A-REF-seq,首次發現m6A的特殊分布模式對基因表達的正調控作用,而有別於之前報導的mRNA降解模型,對m6A機制的解析起到很好的補充。課題組成員為主要貢獻作者的論文發表在Cell、Science Advances、Cell Research、Genome Biology、Nature Communications、Bioinformatics等雜誌上。
承擔課題
主持
國自然優秀青年科學基金項目(2020-2022)
國自然面上項目(2019-2022)
國自然重大研究計畫培育項目(2018-2020)
國自然應急管理項目 (2018-2018)
廣東省自然科學傑出青年基金(2018-2022)
中山大學青年教師重點培育項目(2018-2019)
中山大學“百人計畫”啟動項目(2017-2020)
參與
中山大學重大項目培育和新興學科交叉學科資助計畫項目(2019-2020)
國家重點研發計畫“幹細胞及轉化研究”重點專項(2018-2023)
論文專著
(本實驗室人員姓名加粗,第一作者標#,通訊作者標*)
2019
ZhangZ#,Chen LQ,Zhao YL,Yang CG, Roundtree I,Zhang Z,Ren J,Xie W,He C,Luo GZ*.Single-base mapping of m6A by an antibody-independent method.Science Advances. 5(7):eaax0250 (2019)
Lin X#,Chai G#, Wu Y#, Li J, Chen F, Liu J,Luo G, Tauler J, Du J, Lin S, He C, Wang H*.RNA m6A methylation regulates the epithelial mesenchymal transition of cancer cells and translation of Snail.Nature Communications.10: 2065 (2019)
Liu J#,Luo G#, Sun J, Men L, Ye H, He C, Ren D*.METTL14 is essential for β-cell survival and insulin secretion.Biochim Biophys Acta Mol Basis Dis. 1865(9):2138-2148 (2019)
Zhang LS#, Liu C, Ma H, Dai Q, Sun HL,Luo G, Zhang Z, Zhang L, Hu L, Dong X, He C*.Transcriptome-wide Mapping of Internal N7-Methylguanosine Methylome in Mammalian mRNA.MolecularCell. 74(6):1304-1316 (2019)
Wang X#,Li Y#, Chen W, Shi H, Eren AM, Morozov A, He C,Luo GZ*, Pan T*.Transcriptome-wide reprogramming ofN6-methyladenosine modification by the mouse microbiome.Cell Research. 29(2):167-170 (2019)
Chen Z#, Qi M, Shen B,Luo G, Wu Y, Li J, Lu Z, Zheng Z, Dai Q, Wang H*.Transfer RNA demethylase ALKBH3 promotes cancer progression via induction of tRNA-derived small RNAs.Nucleic Acids Research. 47(5):2533-2545 (2019)
2018
Luo GZ*#,Hao Z#,Luo L,Shen M,Sparvoli D,Zheng Y,Zhang Z,Weng X,Chen K,Cui Q, Turkewitz AP andHe C*.N6-methyldeoxyadenosine directs nucleosome positioning inTetrahymenaDNA.Genome Biology.19:200 (2018)
Yue Y, Liu J, Cui X, Cao J,Luo G, Zhang Z, Cheng T, Gao M, Shu X, Ma H, Wang F, Wang X, Shen B, Wang Y, Feng X, He C, Liu J. VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation.Cell Discovery. 4:10 (2018)
Zhu S, Beaulaurier J, Deikus G, Wu TP, Strahl M, Hao Z,Luo G, Gregory JA, Chess A, He C, Xiao A, Sebra R, Schadt EE, Fang G. Mapping and characterizingN6-methyladenine in eukaryotic genomes using single-molecule real-time sequencing.Genome Research. 28(7):1067-1078 (2018)
2017
Luo GZ& He C. DNAN6-methyladenine in metazoans: functional epigenetic mark or bystander?Nature Structural & Molecular Biology. 24(6):503-506 (2017)
Roundtree IA,Luo GZ, Zhang Z, Wang X, Zhou T, Cui Y, Sha J, Huang X, Guerrero L, Xie P, He E, Shen B, He C. YTHDC1 mediates nuclear export of N6-methyladenosine methylated mRNAs.Elife. pii: e31311 (2017)
Hsu PJ, Zhu Y, Ma H, Guo Y, Shi X, Liu Y, Qi M, Lu Z, Shi H, Wang J, Cheng Y,Luo G, Dai Q, Liu M, Guo X, Sha J, Shen B, He C. Ythdc2 is an N6-methyladenosine binding protein that regulates mammalian spermatogenesis.Cell Research. 27(9):1115-1127 (2017)
2016
Liu J#, Zhu Y#,Luo GZ#, Wang X#, Yue Y, Wang X, Zong X, Chen K, Yin H, Fu Y, Han D, Wang Y, Chen D, He C. Abundant DNA 6mA methylation during early embryogenesis of zebrafish and pig.Nature Communications. 7:13052 (2016)
Luo GZ#, Wang F#, Weng X, Chen K, Hao Z, Yu M, Deng X, Liu J, He C. Characterization of eukaryotic DNA N6-methyladenine by a highly sensitive restriction enzyme-assisted sequencing.Nature Communications.7:11301 (2016)
Liu F, Clark W,Luo G, Wang X, Fu Y, Wei J, Wang X, Hao Z, Dai Q, Zheng G, Ma H, Han D, Evans M, Klungland A, Pan T, He C. ALKBH1-Mediated tRNA Demethylation Regulates Translation.Cell. 167(3):816-828 (2016)
Feng G, Tong M, Xia B,Luo GZ, Wang M, Xie D, Wan H, Zhang Y, Zhou Q, Wang XJ. Ubiquitously expressed genes participate in cell-specific functions via alternative promoter usage.EMBO Reports. 17(9):1304-13 (2016)
2015
Luo GZ, Blanco MA, Greer EL, He C, Shi Y. DNA N6-methyladenine: a new epigenetic mark in eukaryotes?Nature Reviews Molecular Cell Biology.16(12):705-10 (2015)
Fu Y#,Luo GZ#, Chen K, Deng X, Yu M, Han D, Hao Z, Liu J, Lu X, Doré LC, Weng X, Ji Q, Mets L, He C. N6-Methyldeoxyadenosine Marks Active Transcription Start Sites in Chlamydomonas.Cell. 161(4):879-92 (2015) (# co-first author).
Chen K,Luo GZ, He C. High-Resolution Mapping of N-Methyladenosine in Transcriptome and Genome Using a Photo-Crosslinking-Assisted Strategy.Methods Enzymol. 560:161-85 (2015)
Shuai L, Wang Y, Dong M, Wang X, Sang L, Wang M, Wan H,Luo G, Gu T, Yuan Y, Feng C, Teng F, Li W, Liu X, Li T, Wang L, Wang XJ, Zhao XY, Zhou Q. Durable pluripotency and haploidy in epiblast stem cells derived from haploid embryonic stem cells in vitro.J Mol Cell Biol. 7(4):326-37 (2015)
Deng X, Chen K,Luo GZ, Weng X, Ji Q, Zhou T, He C. Widespread occurrence of N6-methyladenosine in bacterial mRNA.Nucleic Acids Research. 43(13):6557-67 (2015)
Chen K, Lu Z, Wang X, Fu Y,Luo GZ, Liu N, Han D, Dominissini D, Dai Q, Pan T and He C. High-ResolutionN6-Methyladenosine (m6A) Map Using Photo-Crosslinking-Assisted m6A Sequencing.Angew Chem Int Ed Engl. 54(5):1587-90 (2015)
2014
Luo GZ#, MacQueen A#, Zheng G#, Duan H, Dore LC, Lu Z, Liu J, Chen K, Jia G*, Bergelson J*, He C*. Unique features of the m6A methylome in Arabidopsis thaliana.Nature Communications. 5:5630 (2014)
Luo GZ, Yang W, Ma YK, Wang XJ. ISRNA: an integrative online toolkit for short reads from high-throughput sequencing data.Bioinformatics. 30(3):434-6 (2014)
Li W, Li X, Li T, Jiang MG, Wan H,Luo GZ, Feng C, Cui X, Teng F, Yuan Y, Zhou Q, Gu Q, Shuai L, Sha J, Xiao Y, Wang L, Liu Z, Wang XJ, Zhao XY, Zhou Q. Genetic modification and screening in rat using haploid embryonic stem cells.Cell Stem Cell. 14(3):404-14 (2014)
Fu L, Shi Z,Luo G, Tu W, Wang X, Fang Z, Li X. Multiple microRNAs regulate human FOXP2 gene expression by targeting sequences in its 3' untranslated region.Mol Brain. 7:71 (2014)
Before 2013
Luo GZ#, Hafner M#, Shi Z, Brown M, Feng GH, Tuschl T, Wang XJ*, Li X*. Genome-wide annotation and analysis of zebra finch microRNA repertoire reveal sex-biased expression.BMC Genomics. 13:727 (2012)
Liu L#,Luo GZ#, Yang W#, Zhao X#, Zheng Q, Lv Z, Li W, Wu HJ, Wang L, Wang XJ, Zhou Q. Activation of the imprinted Dlk1-Dio3 region correlates with pluripotency levels of mouse stem cells.Journal of Biological Chemistry. 285(25):19483-90 (2010) (# co-first author).
Shi Z,Luo G, Fu L, Fang Z, Wang X, Li X. miR-9 and miR-140-5p target FoxP2 and are regulated as a function of the social context of singing behavior in zebra finches.J Neurosci. 33(42):16510-21 (2013)
Wan H, He Z, Dong M, Gu T,Luo GZ, Teng F, Xia B, Li W, Feng C, Li X, Li T, Shuai L, Fu R, Wang L, Wang XJ, Zhao XY, Zhou Q. Parthenogenetic haploid embryonic stem cells produce fertile mice.Cell Research. 23(11):1330-3 (2013)
Zhang Y, Teng F,Luo GZ, Wang M, Tong M, Zhao X, Wang L, Wang XJ, Zhou Q. MicroRNA-323-3p regulates the activity of polycomb repressive complex 2 (PRC2) via targeting the mRNA of embryonic ectoderm development (Eed) gene in mouse embryonic stem cells.J Biol Chem. 288(33):23659-65 (2013)
Li RC, Tao J, Guo YB, Wu HD, Liu RF, Bai Y, Lv ZZ,Luo GZ, Li LL, Wang M, Yang HQ, Gao W, Han QD, Zhang YY, Wang XJ, Xu M, Wang SQ. In Vivo Suppression of MiR-24 Prevents the Transition toward Decompensated Hypertrophy in Aortic-constricted Mice.Circ Res. 112(4):601-5 (2013)
Han J, Chen L,Luo G, Dai B, Wang X, Dai J. Three-dimensional culture may promote cell reprogramming.Organogenesis. 9(2):118-20 (2013)
Liu X, Zhang Y, Tong M, Liu XY,Luo GZ, Xie DF, Ren SF, Bai DH, Wang L, Zhou Q, Wang XJ. Identification of a small molecule 1,4-bis-[4-(3-phenoxy-propoxy)-but-2-ynyl]-piperazine as a novel inhibitor of the transcription factor p53.Acta Pharmacol Sin. 34(6):805-10 (2013)
Li W, Shuai L, Wan H, Dong M, Wang M, Sang L, Feng C,Luo GZ, Li T, Li X, Wang L, Zheng QY, Sheng C, Wu HJ, Liu Z, Liu L, Wang L, Wang XJ, Zhao XY, Zhou Q. Androgenetic haploid embryonic stem cells produce live transgenic mice.Nature.490(7420):407-11 (2012)
Xu M, Wu HD, Li RC, Zhang HB, Wang M, Tao J, Feng XH, Guo YB, Li SF, Lai ST, Zhou P, Li LL, Yang HQ,Luo GZ, Bai Y, Xi JJ, Gao W, Han QD, Zhang YY, Wang XJ, Meng X, Wang SQ. Mir-24 Regulates Junctophilin-2 Expression in Cardiomyocytes.Circ Res. 111(7):837-41 (2012)
Zhang C, Xu Y, Guo S, Zhu J, Huan Q, Liu H, Wang L,Luo G, Wang X, Chong K. Dynamics of brassinosteroid response modulated by negative regulator LIC in rice.PLoS Genet. 8(4):e1002686 (2012)
Du Y, Gao C, Liu Z, Wang L, Liu B, He F, Zhang T, Wang Y, Wang X, Xu M,Luo GZ, Zhu Y, Xu Q, Wang X, Kong W. Upregulation of a disintegrin and metalloproteinase with thrombospondin motifs-7 by miR-29 repression mediates vascular smooth muscle calcification.Arterioscler Thromb Vasc Biol. 32(11):2580-8 (2012)
Zhou Y, Li S, Qian Q, Zeng D, Zhang M, Guo L, Liu X, Zhang B, Deng L, Liu X,Luo G, Wang X, Li J. BC10, a DUF266-containing and Golgi-located type II membrane protein, is required for cell-wall biosynthesis in rice (Oryza sativa L.).Plant J. 57(3):446-62 (2009)
Liu X,Luo G, Bai X, Wang XJ. Bioinformatic analysis of microRNA biogenesis and function related proteins in eleven animal genomes.J Genet Genomics. 36(10):591-601 (2009)