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Systems Immunology

TEL +81-6-6879-8366

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Overview

The Systems Immunology Lab is actively pursuing two major immunology research themes: analysis of immune repertoire sequence data and post-transcriptional regulation of immune responses. In addition, we are developing several core bioinformatics methods, including the MAFFT multiple alignment platform (Katoh, K. & Standley, D. M. Mol Biol Evol (2013)) and the OSCAR protein modeling force field (Liang, S. et al. Bioinformatics 27, 2913-2914 (2011)).

For analysis of immune repertoires, we have taken a structure-based approach. First, we developed a method for high-throughput B cell receptor modeling from sequence data (Yamashita, K. et al. Bioinformatics (2014)). We are currently utilizing sequence and structural features to predict the phenotype of B and T cell receptors in order to develop novel biomarkers and therapeutics.

With regard to post-transcriptional regulation, we are interested in molecular mechanism by which RNA-binding proteins (RBPs) regulate gene expression in immune cells. In order to study RBP-RNA interactions computationally, we have developed a tool for predicting RNA binding sites on proteins (Li, S. et al. Nucleic Acids Res (2014)) and for carrying out flexible protein-RNA docking (Nyati, K. K. et al. Nucleic Acids Res (2017)). These tools have recently been used to investigate the immune-regulatory roles of the RBPs Regnase-1 (Mino, T. et al. Cell (2015)) and Arid5a (Masuda, K. et al. J Exp Med (2016)).

Principal Investigator

Daron M. Standley Professor

Research field

bioinformatics, systems biology

Education history

1998 Ph.D. Chemistry, Columbia University, New York
1993 BS Physics, Harvey Mudd College, Claremont, CA

Research and career history

2015.4- Professor, IFReC, Osaka University
2014.10 Professor, Institute for Virus Research, Kyoto University 
2008.10 Associate Professor, IFReC, Osaka University
2003.4 Senior Researcher, Protein Data Bank Japan, Institute for Protein Research, Osaka University (-2008.9)
1998.9 Scientific Software Developer Schrodinger, Inc. (-2003.3)

Prize

2014 K. Katoh: Young Scientist Initiative Award from the Society of Evolutionary Studies, Japan, 2014.
2009 D. Standley: 2009 Prize for Outstanding Achievement in Education and Research at Osaka University

Members

  • Daron M. Standley Professor
    standleybiken.osaka-u.ac.jp
  • Kazutaka Katoh　Associate Professor
    katohbiken.osaka-u.ac.jp
  • Soyoung Park 　Associate Professor
    sparkifrec.osaka-u.ac.jp
  • Songling Li　Associate Professor
    slliifrec.osaka-u.ac.jp

Achievements

Publications

  • T Nakamura, KD Yamada, K Tomii, K Katoh Parallelization of MAFFT for large-scale multiple sequence alignments (2018).
     
  • S Teraguchi, Y Kumagai Estimation of diffusion constants from single molecular measurement without explicit tracking (2018).
     
  • K Katoh, J Rozewicki, KD Yamada MAFFT online service: multiple sequence alignment, interactive sequence choice and visualization (2017).
     
  • M Sasai, N Sakaguchi, JS Ma, S Nakamura, T Kawabata, H Bando, Y Lee. et al. Essential role for GABARAP autophagy proteins in interferon-inducible GTPase-mediated host defense (2017).
     
  • Nyati, K. K. et al. TLR4-induced NF-kappaB and MAPK signaling regulate the IL-6 mRNA stabilizing protein Arid5a. Nucleic Acids Res (2017).
     
  • Yokogawa, M. et al. Structural basis for the regulation of enzymatic activity of Regnase-1 by domain-domain interactions. Sci Rep 6, 22324 (2016)
     
  • Katoh, K. & Standley, D. M. A simple method to control over-alignment in the MAFFT multiple sequence alignment program. Bioinformatics (2016)
     
  • Masuda, K. et al. Arid5a regulates naive CD4+ T cell fate through selective stabilization of Stat3 mRNA. J Exp Med (2016).
     
  • Kamikawa, Y. et al. Design of a protein tag and fluorogenic probe with modular structure for live-cell imaging of intracellular proteins. Chemical Science 7, 308-314 (2016)
     
  • Yamashita, K. et al. Kotai Antibody Builder: automated high-resolution structural modeling of antibodies. Bioinformatics 30, 3279-3280 (2014).
     
  • Li, S., Yamashita, K., Amada, K. M. & Standley, D. M. Quantifying sequence and structural features of protein-RNA interactions. Nucleic Acids Res 42, 10086-10098 (2014).
     
  • Uehata, T. et al. Malt1-induced cleavage of regnase-1 in CD4(+) helper T cells regulates immune activation. Cell 153, 1036-1049 (2013).
     
  • Katoh, K. & Standley, D. M. MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Mol Biol Evol 30, 772-780 (2013).
     
  • Mino, T. et al. Regnase-1 and Roquin Regulate a Common Element in Inflammatory mRNAs by Spatiotemporally Distinct Mechanisms. Cell 161, 1058-1073 (2015).
     
  • Liang, S., Zheng, D., Zhang, C. & Standley, D. M. Fast and accurate prediction of protein side-chain conformations. Bioinformatics 27, 2913-2914 (2011).
     
  • Kitamura, A. et al. A mutation in the immunoproteasome subunit PSMB8 causes autoinflammation and lipodystrophy in humans. J Clin Invest 121, 4150-4160 (2011)
     
  • Iwasaki, H. et al. The IkappaB kinase complex regulates the stability of cytokine-encoding mRNA induced by TLR-IL-1R by controlling degradation of regnase-1. Nat Immunol 12, 1167-1175 (2011).
     
  • Satoh, T. et al. The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection. Nat Immunol 11, 936-944 (2010)
     
  • Yamamoto, M. et al. A single polymorphic amino acid on Toxoplasma gondii kinase ROP16 determines the direct and strain-specific activation of Stat3. J Exp Med 206, 2747-2760 (2009).
     
  • Standley, D. M., Yamashita, R., Kinjo, A. R., Toh, H. & Nakamura, H. SeSAW: balancing sequence and structural information in protein functional mapping. Bioinformatics 26, 1258-1259 (2010)
     
  • Matsushita, K. et al. Zc3h12a is an RNase essential for controlling immune responses by regulating mRNA decay. Nature 458, 1185-1190 (2009).
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