1 FBC Lett., No. 45 (2014) (2014 年 7 月) 夢への責任 藤井 郁雄 齊藤
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1 FBC Lett., No. 45 (2014) (2014 年 7 月) 夢への責任 藤井 郁雄 齊藤
FBC Lett., No. 45 (2014) 2014 2 4 夢への責任 大阪府立大学大学院理学系研究科 7 藤井 郁雄 4 RNA ワールドから iPS 細胞へ -生命起源と細胞構築原理の探求京都大学 iPS 細胞研究所 白眉センター 齊藤 博英 9 バクテリア融合チャンバー -細胞の再構成に向けた人工物との融合田端 和仁 東京大学大学院工学研究科 14 14. 18. 京都大学大学院工学研究科 博士課程1年 東北大学多元物質科学研究所 博士課程2年 21. 25 九州大学大学院薬学研究院 助教 河 陸 上松 亮平 田畑 栄一 カリフォルニア工科大学留学体験記 Division of Chemistry and Chemical Engineering, California Institute of Technology 30 田村 朋則 第8回 バイオ関連化学シンポジウム 第 41 回 国際核酸化学シンポジウム(ISNAC2014) 第 24 回 バイオ・高分子シンポジウム 14-1 バイオ・高分子研究会 人工光合成国際会議 2014 第 17 回 生命化学研究会 受賞、異動 編集後記 1 No.45 (2014 July) 2008 2014 STAP / 4 4 O iPS … R O 2 STAP No.45 (2014 July) O O 2014 3 6 No.45 (2014 July) [email protected] 1. RNA RNA RNA RNA RNA Jack Szostak David Bartel RNA RNA Szostak RNA RNA tRNA tRNA RNA RNA RNA RI tRNA 1,2,3 RNA 4 4 No.45 (2014 July) 2. RNA5 RNA 2005 RNA (RNA ) mRNA RNA RNA (RNA ) RNA ( ) 1 1 RNA RNA mRNA mRNA (UTR) mRNA L7Ae RNA 6 L7Ae RNA (K-turn) K-turn mRNA L7Ae L7Ae mRNA 3. 5 mRNA mRNA mRNA RNA mRNA ( 2) 7 mRNA mRNA 2 5 5 RNA No.45 (2014 July) 5 5 cis UTR UTR mRNA (2) mRNA (2)' gene'of'interest (1) (1) RNA ' $ (1)$ (2)$ 4. RNA RNA RNA 8 RNA RNA RNA OFF ON 3 RNA mRNA mRNA mRNA (NMD) NMD mRNA ON OFF ON OFF mRNA 1 1 6 ON No.45 (2014 July) ON' . . OFF (intron) IRES 0 0 1 1 mRNA' . ON (intron) IRES mRNA 5. RNARNAL7Ae-K-turn L7Ae 60 K-turn RNA L7Ae-K-turn ( 4 ) 9 K-turn L7Ae 60 AFM RNA 1 L7Ae ( 10nm RNA 7 4 ) RNA No.45 (2014 July) 6. RNA 2010 iPS 2011 iPS RNA RNA RNA RNA RNP RNA-Protein RNA RNP 10 iPS 1. Saito, H., Kourouklis, D. & Suga, H. An in vitro evolved precursor tRNA with aminoacylation activity. EMBO J 20, 1797-1806 (2001). 2. Saito, H. & Suga, H. A ribozyme exclusively aminoacylates the 3'-hydroxyl group of the tRNA terminal adenosine. J Am Chem Soc 123, 7178-7179 (2001). 3. Saito, H., Watanabe, K. & Suga, H. Concurrent molecular recognition of the amino acid and tRNA by a ribozyme. RNA 7, 1867-1878 (2001). 4. Saito, H. & Inoue, T. Synthetic biology with RNA motifs. Int J Biochem Cell Biol 41, 398-404 (2009). 5. Saito, H. et al. Synthesis of functional proteins by mixing peptide motifs. Chem Biol 11, 765-773 (2004). 6. Saito, H. et al. Synthetic translational regulation by an L7Ae-kink-turn RNP switch. Nat Chem Biol 6, 71-78 (2010). 7. Endo, K., Stapleton, J.A., Hayashi, K., Saito, H. & Inoue, T. Quantitative and simultaneous translational control of distinct mammalian mRNAs. Nucleic Acids Res 41, e135 (2013). 8. Endo, K., Hayashi, K., Inoue, T. & Saito, H. A versatile cis-acting inverter module for synthetic translational switches. Nat Commun 4, 2393 (2013). 9. Ohno, H. et al. Synthetic RNA-protein complex shaped like an equilateral triangle. Nat Nanotechnol 6, 116-120 (2011). 10. Hagiya, M., Konagaya, A., Kobayashi, S., Saito, H. & Murata, S. Molecular Robots with Sensors and Intelligence. Acc Chem Res 47, 1681-1690 (2014). 8 No.45 (2014 July) [email protected] 1. 2. Craig Venter [1] 1Mbp Mycoplasma mycoides Mycoplasma capricolum Mycoplasma mycoides JCVI-syn 1.0 1 9 No.45 (2014 July) 3. ? 2 mg/ml 10 1000 2 4. ? 2 1 5 m 1 1 digital ELISA [2,3] fL 10 fL No.45 (2014 July) 1 [4] 1 2 3 GFP a 3 GFP 5. DNA 2 ATP GFP 4 2 3 5 a GFP 5mM ATP ATP ATP DNA DNA GFP 6 GFP GFP GFP 11 4 GFP 1 No.45 (2014 July) GFP Background GFP DNA DNA 6. ? 5 7 7. 6 GFP 7 12 No.45 (2014 July) [1] D.G. Gibson, J.I. Glass, C. Lartigue, V.N. Noskov, R.Y. Chuang, M.A. Algire, G.A. Benders, M.G. Montague, L. Ma, M.M. Moodie, C. Merryman, S. Vashee, R. Krishnakumar, N. Assad-Garcia, C. Andrews-Pfannkoch, E.A. Denisova, L. Young, Z.Q. Qi, T.H. Segall-Shapiro, C.H. Calvey, P.P. Parmar, C.A. Hutchison, 3rd, H.O. Smith, J.C. Venter, Creation of a bacterial cell controlled by a chemically synthesized genome, Science, 329 (2010) 52-56. [2] S. Sakakihara, S. Araki, R. Iino, H. Noji, A single-molecule enzymatic assay in a directly accessible femtoliter droplet array, Lab on a Chip, 10 (2010) 3355-3362. [3] S.H. Kim, S. Iwai, S. Araki, S. Sakakihara, R. Iino, H. Noji, Large-scale femtoliter droplet array for digital counting of single biomolecules, Lab on a Chip, 12 (2012) 4986-4991. [4] R. Watanabe, D. Fujita, K.V. Tabata, L. Yamauchi, N. Soga, S.H. Kim, H. Suga, H. Noji, High throughput formation of sub-million lipid membrane arrays for measuring membrane protein activities, proceedings of MicroTAS 2013, (2013) 1314-1316. 13 No.45 (2014 July) [email protected] 2014 3 2014 4 Near-infrared dye loaded polymeric nanoparticles for cancer imaging and therapy and cellular response after laser-induced heating T. Lei, A. F. Fernandez, R. Manchanda, Y. -C. Hung, and A. J. McGoron, Beilstein J. Nanotechnol. 2014, 5, 313-322. 100 nm EPR MRI PET 700-900 nm ICG ICG ICG HIF-1 HIF-1 HIF-1 HIF-1 HSP HSP ICG HSP 14 No.45 (2014 July) PGMD IR820 ICG IR820-PGMD PGMD IR-820 IR820 IR820-PGDM Figure 1 IR820-PGMD 24 MES-SA/Dx5 ROS VEGF HIF-1 IR820-PMGD ICG HIF-1 IR820-PMGD Figure 1 IR820 Superparamagnetic hollow hybrid nanogels as a potential guidable vehicle system of stimuli-mediated MR imaging and multiple cancer therapeutics W. -H. Chiang, V. -T. Ho, H. -H. Chen, W. -C. Huang, Y. -F. Huang, S. -C. Ling, C. -S. Chern, and H. -C, Chiu, Langmuir 2013, 29, 6434-6443. DDS MRI SPIONs SPIONs SPIONs PEG MES PAA PNIPA Figure 2 MES pH 190 nm -18.5 mV SPIONs pH DOX T2-type MRI MRI pH Figure 2 15 No.45 (2014 July) in vivo MRI HeLa SPIONs DOX DOX HeLa Figure 2 pH SPIONs MRI SiO2@YBO3: Eu3+ hollow mesoporous spheres for drug delivery vehicle G. Yang, S. Gai, F. Qu, and P. Yang, ACS Appl. Mater. Interfaces 2013, 5, 5788-5796 DDS DDS DDS 16 No.45 (2014 July) DDS Figure 3 Figure 3 ( DDS ) 200 90 nm 180 300 nm TEOS (HMSs@YBO3:Eu3+) PBS HMSs@YBO3:Eu3+ DOX 30-40% HMSs@YBO3:Eu3+ DOX DOX pH DOX L929 HMSs@YBO3:Eu3+ 200 µg/mL MTT DDS HMSs@YBO3:Eu3+ DDS 17 No.45 (2014 July) 2 [email protected] PS 1 2 Antisense therapies for cardiovascular/metabolic diseases R. S. Geary, R. Crooke, S. Bhanot, W. Singleton, Drug Discov. Today Ther. Strateg., 2014, in press. (DOI: 10.1016/j.ddstr.2013.06.001) RNA RNase H RNAi Mipomersen KYNAMROTM apoB-100 Gap motif RNase H RNAi Phase 3 ALN-PCS PCSK9 1 Phase 1 PCSK9 ALN-PCS Base O LDL HO Base R O O P O S Base Base O R O O P S O O n O O P S O O n LDL Base R O O P O S n O R OH R= O O 1. Gap motif 2 Ultrasmall gold nanoparticles as carriers for nucleus-based gene therapy due to size-dependent nuclear entry S. Huo, S. Jin, X. Ma, X. Xue, K. Yang, A. Kumar, P. C. Wang, J. Zhang, Z. Hu, X. -J. Liang, ACS Nano, 2014, 5852-5862. Triplex-forming oligonucleotides TFOs TFO DNA DNA DNase Au-NPs 18 No.45 (2014 July) 50 nm TFO Tiopronin nm 6 nm Au-TIOP NPs 2a 10 nm 16 nm 2 2b FITC MCF-7 2 nm Au-FITC NP 3 9 nm 2 nm Au-TIOP NP POY2T TFO MCCF-7 c-myc Au-POY2T NPs, 24 h 2c Au-POY2T NPs c-myc PCR TFO POT2T Au-POY2T NPs 3 80 % 20% TFO 2 nm (a) (c) (b) 2. (a) Au-NPs American Chemical Society 2, 6 nm ; (b) Au-NPs 10, 16 nm (c) Au-POY2T 3. A 2 nm, B 6 nm, C 10 nm, D 16 nm Au-FITC NPs ; : Au-FITC NPs; : MCF-7 Copyright 2014 American Chemical Society 19 Copyright 2014 4. (Copyright 2014 American Chemical Society) No.45 (2014 July) Versatile RNA interference nanoplatform for systemic delivery of RNAs K. Y. Choi, O. F. Silvestre, X. Huang, K. H. Min, G. P. Howard, N. Hida, A. J. Jin, N. Carvajal, S. W. Lee, J. -I. Hong, X. Chen, ACS Nano, 2014, 8 (5), 4559-4570. RNA RNAi RNAi siRNA miRNA RNA RNA RNA 5βHA-NP CD44 CD44 Zn(II)-dipicolylamine DPA/Zn HA-NP RNA HDz/RNA RNA HDz/RNA CaP CaP-HDz/RNA 5 CaP-HDz/RNA CaP DPA/Zn RNA RNA CaP RNA HA-NP HA-NP CaP-HDz/RNA RNA in vivo siRNA RNAi fLuc HA-NP siLuc DPA/Zn 5. CaP-HDz/RNA Control: PBS, Non-cording (a) Drug (Optional) CaP RNA (Copyright 2014 American Chemical Society) (b) sequence: siNC fLuc 6 CaP-HDz/RNA siRNA RNAi 6. (a) RNA : : ; (b) 3 (Copyright 2014 American Chemical Society) 20 3 No.45 (2014 July) [email protected] DNA 2008 4 photo affinity labeling A propofol binding site on mammalian GABAA receptors identified by photolabeling G. M. S. Yip, Z. -W. Chen, C. J. Edge, E. H. Smith, R. Dickinson, E. Hohenester, R. R. Townsend, K. Fuchs, W. Sieghart, A. S. Evers, N. P. Franks Nature Chem. Biol. 2013, 9, 715-720. Propofol 1 1 GABA γGABAA 5 GABAA Cl– 5 β3 propofol GABAA β3 photo affinity labeling trifluoromethyl diazirine propofol GABAA Sf9 1 propofol GABAA α1 21 No.45 (2014 July) ortho-propofol diazirine(o-PD) β3 o-PD(dPD) m/z LC/MS o-PD dPD 1 m/z 1 o-PD ( o-PD MS GABAA 2) H267 β3 His Ala o-PD H267 propofol propofol β3 5 GABAA 1 β3 β3 propofol GPCR G protein-coupled receptor photo affinity labeling Palladium-triggered deprotection chemistry for protein activation in living cells J. Li, J. Yu, J. Zhao, J. Wang, S. Zheng, S. Lin, L. Chen, M. Yang, S. Jia, X. Zhang, P. R. Chen, Nature Chem. 2014, 6, 352-361. 1 chemical rescue strategy ε-NH2 Lys propargyl (Pd) ( 3) rhodamine 110 ( NH2 propargyloxycarbonyl(Proc) 4a) (Pd 22 allyloxycarbonyl(Alloc) ) ( 4b) Proc No.45 (2014 July) Pd C5 phosphothreonine lyase 1 OspF OspF ) OspF Lys134 lyase( Lys134 ε-NH2 Proc Lys (OspF-K134-Proc-Lys) OspF-K134-Proc-Lys ( (Proc-Lys) HeLa Pd Erk(p-Erk) p-Erk ( OspF-K134-Proc-Lys 5b ( Proc-Lys 5a) ( 1,2) 5b 5b 4) Pd Proc-Lys 3,6,7) OspF-K134-Proc-Lys Pd The hepatitis B virus preS1 domain hijacks host trafficking proteins by motif mimicry M. C. Jürgens, J. Vörös, G. J. P. Rautureau, D. A. Shepherd, V. E. Pye, J. Muldoon, C. M. Johnson, A. E. Ashcroft, S. M. V. Freund, N. Ferguson Nature Chem. Biol. 2013, 9, 540-547. B HBV 3 1 L protein 2 1 + preS2 PreS cytosol e-preS L preS1 i-preS L PreS γ2-adaptin 6a lumen 6b i-preS L EAR 6c γ2-EAR 23 γ No.45 (2014 July) i-preS L γ2-adaptin NMR ITC i-preS L i-preS L γ2-EAR PreS PreS1 δ γ2-EAR PreS1 HSQC heteronuclear single quantum coherence γ chemical shift perturbation CSP PreS1 29-41 δ δ 7 δ γ2-EAR 29-41 preS1 ITC γ2-EAR 9-16 γ2-EAR 59-68 3 γ2-EAR 29-36 1 15 PreS1 PreS1 1 N- H heteronuclear NOE ion mobility spectrometry-mass spectrometry IMS-MS IMS-MS IMS m/z PreS1 extended form intrinsically disordered protein; IDP NMR γ2-EAR 15 IMS-MS 1 N- H heteronuclear NOE 2 γ2-EAR-preS1 preS1 γ2-EAR HBV NMR ITC IMS-MS IDP IDP 2 IDP IDP 24 No.45 (2014 July) [email protected] 2013 3 5 Caltech Linda Hsieh-Wilson Caltech No.18 Deep Caltech Caltech 1 1 4 Benjamin G. Davis 3 D2 3 3 1 Ben Davis Glycobiology ( ) D3 12 Linda Linda 25 No.45 (2014 July) CV Linda P. G. 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Kyung Byung Yoon Sogang Univ. 40,000 25,000 9 21 ICARP2014 E-mail: [email protected] http://artificial-photosynthesis.net/ICARP2014/ 36 No. 45 (2014 July) 第 17 回 生命化学研究会 ∼生命化学の大海原を探る∼ http://res.tagen.tohoku.ac.jp/FBC/ 2015 1 8 13 9 780-0862 12 1-3-35 TEL: 088-822-0131 http://www.sansuien.co.jp/ 40 720 → 15 200 JR 20 13,000 10,000 200 7,000 E-mail 11/18 80 40 11/18 A4 http://res.tagen.tohoku.ac.jp/FBC/ __ __ 558-8585 __ ____ 3-3-138 E-mail [email protected] Tel: 06-6605-2696 Fax: 06-6605-2785 37 No. 45 (2014 July) 25 31 2014 2014 1 3 1 924-0838 3-1 E-mail: [email protected] 38 No. 45 (2014 July) No. 45 45 10 T … ? ? S-J Bern?… No. 46 2014 10 26 6 20 [email protected] 39 in