Systems Immunology

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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
+81-6-6879-8366
standley atmark biken.osaka-u.ac.jp
Education history
1998Ph.D. Chemistry, Columbia University, New York
1993BS 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
2003.4-2008.9Senior Researcher, Protein Data Bank Japan, Institute for Protein Research, Osaka University
1998.9-2003.3Scientific Software Developer Schrodinger, Inc.

Members

Kazutaka Katoh Associate Professor
katoh atmark biken.osaka-u.ac.jp
Li Songling Assistant Professor
slli atmark ifrec.osaka-u.ac.jp
Rozewicki John James Researcher
jroze atmark biken.osaka-u.ac.jp
 
 

Publications

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).

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