• Laboratory
  • Ken Kurokawa , Nobutaka Nakashima , Takuji Yamada

Ken Kurokawa
Ken Kurokawa

Ken Kurokawa

Professor, Department of Biological Information
PhD 2000, Kyushu University
E-mail: ken(at)bio.titech.ac.jp
Office: Room 201, Midorigaoka-6 building, Ookayama campus

Nobutaka Nakashima
Nobutaka Nakashima

Nobutaka Nakashima

Associate Professor, Department of Biological Information
PhD 2000, Kyushu University
E-mail: nnakashima(at)bio.titech.ac.jp
Office: Room 201, Midorigaoka-6 building, Ookayama campus

Areas of Research: Bacteriology, Applied microbiology, Genome sciences, RNA sciences.

Keywords: Metagenome, Biofilm, Antisense RNAs, Microbial community, Bioenergy, Biomass utilization.


Research interest:

 Our research is focused on analyzing and utilizing bacterial populations without isolating individual bacteria.

 Various bacteria live in soil, water, air, and the bodies of animals. We think that there are two problems in current bacterial researches. First, most researches are carried out using isolated pure cultures, but it is said that only a small percentage of the microbes that exist on earth has been isolated so far. Second, some bacteria live in the planktonic state whereas others live as sessile cells; although the majority of microbes on earth is thought to be in the latter state, they are preferentially cultured in planktonic states in laboratories. As one familiar example, slimy structures are routinely found on kitchen sinks, which is called biofilm and made of a variety of sessile bacteria.

We believe that industrially and pharmaceutically valuable genes are buried in untouched bacterial communities. In other words, bacterial communities are full of treasures. Also, emergence of biofilms is problematic in medical and sanitary fields. Therefore, we are trying to do the following researches.

  1. Establishing model bacterial communities and biofilms that are re-producible for a long time in laboratories.
  2. Investigating how biofilms are constructed and developing methods to remove them.
  3. Discovering valuable genes that are sleeping in bacterial communities without isolating bacteria (metagenome analysis).
  4. Combating one unwanted bacterium in populations to keep bacterial communities (flora) in a favorable state.


Selected publications

  1. Nakamura, Y., Yamamoto, N., Kino, Y., Yamamoto, N., Kamei, S., Mori, H., Kurokawa, K., and Nakashima, N. (2016) Establishment of a multi-species biofilm model and metatranscriptomic analysis of biofilm and planktonic cell communities. Appl. Microbiol. Biotechnol.100, 7263-7279.
  2. Akita, H., Nakashima, N., and Hoshino, T. (2015) Bacterial production of isobutanol without expensive reagents. Appl. Microbiol. Biotechnol.99, 991-999.
  3. Nakashima, N., Akita, H., and Hoshino, T. (2014) Establishment of a novel gene expression method, BICES (biomass-inducible chromosome-based expression system), and its application to the production of 2,3-butanediol and acetoin. Metab. Eng. 25, 204–214.
  4. Nakashima, N., Ohno, S., Yoshikawa, K., Shimizu, H., and Tamura, T. (2014) A vector library for silencing central carbon-metabolism genes with antisense RNAs in Escherichia coli. Appl. Environ. Microbiol. 80, 564–573.
  5. Nakashima, N., and Tamura, T. (2013) Gene silencing in Escherichia coli using antisense RNAs expressed from doxycycline-inducible vectors. Lett. Appl. Microbiol. 56, 436–442.
  6. Nakashima, N., and Tamura, T. (2012) A new carbon catabolite repression mutation of Escherichia coli, mlc*, and its use for producing isobutanol. J. Biosci. Bioeng. 114, 38–44.
  7. Nakashima, N., Goh, S., Good, L., and Tamura, T. (2012) Multiple-gene silencing using antisense RNAs in Escherichia coli. Meth. Mol. Biol. 815, 307-319.
  8. Nakashima, N., Goh, S., and Tamura, T. (2012) Subtracting gene function by gene silencing and disruption in bacteria. Curr. Biotechnol. 9, 166-174.


Takuji Yamada
Takuji Yamada

Takuji Yamada

Associate Professor, Department of Biomolecular Engineering
PhD 1993, Tokyo Institute of Technology
E-mail: yamada(at)bio.titech.ac.jp
Office: Room201A, M6 building, Oookayama campus

Areas of Research: Bioinformatics, Metagenomics, Genomics

Keywords: Human microbiome, Data visualization, Database, Functional prediction

Research interest:

Various microbial species construct functional eco-system in our intestine. Next generation sequencers and metagenomic analyses facilitate the comprehensive studies for human microbiome, including un-culturable bacteria. In particular, gut microbome studies accelerate the field of human microbiome studies because of their direct effects to human health.

Yamada-lab is mainly focusing on the human microbiome study based on bioinformatics, functional analysis, and database construction. We are also working for data visualization for biological big data, such as genome, or gene expression data.

Selected publications

  1. Matsuki T, Yahagi K, Mori H, Matsumoto H, Hara T, Tajima S, Ogawa E, Kodama H, Yamamoto K, Yamada T, Matsumoto S, Kurokawa K. A key genetic factor for fucosyllactose utilization affects infant gut microbiota development. Nat Commun. 2016 Jun 24;7:11939. doi: 10.1038/ncomms11939.
  2. Nishimoto Y, Mizutani S, Nakajima T, Hosoda F, Watanabe H, Saito Y, Shibata T, Yachida S, Yamada T . High stability of faecal microbiome composition in guanidine thiocyanate solution at room temperature and robustness during colonoscopy. Gut 2016 Jun 23.
  3. Moriya Y, Yamada T, Okuda S, Nakagawa Z, Kotera M, Tokimatsu T, Kanehisa M, Goto S. Identification of Enzyme Genes Using Chemical Structure Alignments of Substrate-Product Pairs. J Chem Inf Model. 2016 Mar 28;56(3):510-6.
  4. Wang T, Mori H, Zhang C, Kurokawa K, Xing XH, Yamada T. DomSign: a top-down annotation pipeline to enlarge enzyme space in the protein universe. BMC Bioinformatics;16(1):96 (2015)
  5. Uchiyama T, Irie M, Mori H, Kurokawa K, Yamada T. FuncTree: Functional Analysis and Visualization for Large-Scale Omics Data. PLoS One. 2015 May 14;10(5):e0126967. doi: 10.1371/journal.pone.0126967. PubMed PMID: 25974630
  6. Zeller G, Tap J, Voigt AY, Sunagawa S, Kultima JR, Costea PI, Amiot A, Böhm J, Brunetti F, Habermann N, Hercog R, Koch M, Luciani A, Mende DR, Schneider MA, Schrotz-King P, Tournigand C, Tran Van Nhieu J, Yamada T, Zimmermann J, Benes V, Kloor M, Ulrich CM, von Knebel Doeberitz M, Sobhani I, Bork P. Potential of fecal microbiota for early-stage detection of colorectal cancer. Mol Syst Biol;10:766 (2014)
  7. Li J, Jia H, Cai X, Zhong H, Feng Q, Sunagawa S, Arumugam M, Kultima JR, Prifti E, Nielsen T, Juncker AS, Manichanh C, Chen B, Zhang W, Levenez F, Wang J, Xu X, Xiao L, Liang S, Zhang D, Zhang Z, Chen W, Zhao H, Al-Aama JY, Edris S, Yang H, Wang J, Hansen T, Nielsen HB, Brunak S, Kristiansen, Guarner F, Pedersen O, Doré J, Ehrlich SD, Pons N, Le Chatelier E, Batto JM, Kennedy S, Haimet F, Winogradski Y, Pelletier E, LePaslier D, Artiguenave F, Bruls T, Weissenbach J, Turner K,Parkhill J, Antolin M, Casellas F, Borruel N, Varela E, Torrejon A, Denariaz G, Derrien M, van Hylckama Vlieg JE, Viega P, Oozeer R, Knoll J,Rescigno M, Brechot C, M'Rini C, Mérieux A, Yamada T, Tims S, Zoetendal EG, Kleerebezem M, de Vos WM, Cultrone A, Leclerc M, Juste C,Guedon E, Delorme C, Layec S, Khaci G, van de Guchte M, Vandemeulebrouck G, Jamet A, Dervyn R, Sanchez N, Blottière H, Maguin E, Renault P,Tap J, Mende, Bork P, Wang J. An integrated catalog of reference genes in the human gut microbiome. Nat. Biotechnol. 32, 834–41 (2014)
  8. Nielsen HB, Almeida M, Juncker AS, Rasmussen S, Li J, Sunagawa S, Plichta DR, Gautier L, Pedersen AG, Le Chatelier E, Pelletier E, Bonde I, Nielsen T, Manichanh C, Arumugam M, Batto JM, Quintanilha Dos Santos MB, Blom N, Borruel N, Burgdorf KS, Boumezbeur F, Casellas F, Doré J, Dworzynski P, Guarner F, Hansen T, Hildebrand F, Kaas RS, Kennedy S, Kristiansen K, Kultima JR, Léonard P, Levenez F, Lund O, Moumen B, Le Paslier D, Pons N, Pedersen O, Prifti E, Qin J, Raes J, Sørensen S, Tap J, Tims S, Ussery DW, Yamada T; MetaHIT Consortium, Renault P, Sicheritz-Ponten T, Bork P, Wang J, Brunak S, Ehrlich SD; MetaHIT Consortium. Identification and assembly of genomes and genetic elements in complex metagenomic samples without using reference genomes. Nat Biotechnol.32(8):822-8 (2014)
  9. Waller, AS., Yamada, T., Kristensen, DM., Kultima, JR., Sunagawa, S., Koonin, EV., Bork, P. Classification and quantification of bacteriophage taxa in human gut metagenomes. ISME J. 8(7):1391-402 (2014)
  10. Le Chatelier E, Nielsen T, Qin J, Prifti E, Hildebrand F, Falony G, Almeida M, Arumugam M, Batto JM, Kennedy S, Leonard P, Li J, Burgdorf K, Grarup N, Jørgensen T, Brandslund I, Nielsen HB, Juncker AS, Bertalan M, Levenez F, Pons N, Rasmussen S, Sunagawa S, Tap J, Tims S, Zoetendal EG, Brunak S, Clément K, Doré J, Kleerebezem M, Kristiansen K, Renault P, Sicheritz-Ponten T, de Vos WM, Zucker JD, Raes J, Hansen T; MetaHIT consortium, Bork P, Wang J, Ehrlich SD, Pedersen O, Guedon E, Delorme C, Layec S, Khaci G, van de Guchte M, Vandemeulebrouck G, Jamet A, Dervyn R, Sanchez N, Maguin E, Haimet F, Winogradski Y, Cultrone A, Leclerc M, Juste C, Blottière H, Pelletier E, LePaslier D, Artiguenave F, Bruls T, Weissenbach J, Turner K, Parkhill J, Antolin M, Manichanh C, Casellas F, Boruel N, Varela E, Torrejon A, Guarner F, Denariaz G, Derrien M, van Hylckama Vlieg JE, Veiga P, Oozeer R, Knol J, Rescigno M, Brechot C, M'Rini C, Mérieux A, Yamada T. Richness of human gut microbiome correlates with metabolic markers. Nature. 29;500(7464):541-6 (2014)
  11. *Yamada, T., Waller, A., Raes, J., Zeleznik, A., Perchat, N., Perret, A., Salanoubat, M., Patil, K.R., Weissenbach, J. and Bork, P. Prediction and identification of sequences coding for orphan enzymes using genomic and metagenomic neighibors; Molecular Systems Biology, 8:581 (2012)
  12. *Yamada, T., Letunic, I., Okuda, S., Kanehisa, M. and Bork, P. iPath2.0: interactive pathway explorer; Nucleic Acids Res, 39 W412-415 (2011)
  13. Arumugam, M., Raes, J., Pelletier, E., Le Paslier, D., Yamada, T., Mende, D.R., Fernandes, G.R., Tap, J., Bruls, T., Batto, J.M., Bertalan, M., Borruel, N., Casellas, F., Fernandez, L., Gautier, L., Hansen, T., Hattori, M., Hayashi, T., Kleerebezem, M., Kurokawa, K., Leclerc, M., Levenez, F., Manichanh, C., Nielsen, H.B., Nielsen, T., Pons, N., Poulain, J., Qin, J., Sicheritz-Ponten, T., Tims, S., Torrents, D., Ugarte, E., Zoetendal, E.G., Junwang, Guarner, F., Pedersen, O., de Vos, W.M., Brunak, S., Dore, J., Consortium, M., Weissenbach, J., Ehrlich, S.D. and Bork, P. Enterotypes of the human gut microbiome. Nature. 473 (7346), 174-180 (2011)
  14. Raes, J., Letunic, I., Yamada, T., Jensen, L.J. and Bork, P. (2011) Toward molecular trait-based ecology through integration of biogeochemical, geographical and metagenomic data. Mol Syst Biol, 7, 473 (2011).
  15. Colbourne, J.K., Pfrender, M.E., Gilbert, D., Thomas, W.K., Tucker, A., Oakley, T.H., Tokishita, S., Aerts, A., Arnold, G.J., Basu, M.K., Bauer, D.J., Caceres, C.E., Carmel, L., Casola, C., Choi, J.H., Detter, J.C., Dong, Q., Dusheyko, S., Eads, B.D., Frohlich, T., Geiler-Samerotte, K.A., Gerlach, D., Hatcher, P., Jogdeo, S., Krijgsveld, J., Kriventseva, E.V., Kultz, D., Laforsch, C., Lindquist, E., Lopez, J., Manak, J.R., Muller, J., Pangilinan, J., Patwardhan, R.P., Pitluck, S., Pritham, E.J., Rechtsteiner, A., Rho, M., Rogozin, I.B., Sakarya, O., Salamov, A., Schaack, S., Shapiro, H., Shiga, Y., Skalitzky, C., Smith, Z., Souvorov, A., Sung, W., Tang, Z., Tsuchiya, D., Tu, H., Vos, H., Wang, M., Wolf, Y.I., Yamagata, H., Yamada, T., Ye, Y., Shaw, J.R., Andrews, J., Crease, T.J., Tang, H., Lucas, S.M., Robertson, H.M., Bork, P., Koonin, E.V., Zdobnov, E.M., Grigoriev, I.V., Lynch, M. and Boore, J.L. The ecoresponsive genome of Daphnia pulex. Science, 331 (6017), 555-561 (2011)
  16. Qin. J., Li. R., Raes. J., Arumugam. M., Burgdorf. KS., Manichanh. C., Nielsen. T., Pons. N., Levenez. F., Yamada. T., Mende. D., Li. J., Xu. J., Li. S., Li. D., Cao. J., Wang. B., Liang. H., Zheng. H., Xie. Y., Tap. J., Lepage. P., Bertalan. M., Batto. J., Hansen. T., Paslier. DL., Linneberg. A., Nielsen. HB., Pelletier. E., Renault. P., Sicheritz-Ponten. T., Turner. K., Zhu. H., Yu. C., Li. S., Jian. M., Zhou. Y., Li. Y., Zhang. X., Li. S., Yang. H., Wang. J., Brunak. S., Doré. J., Guarner. F., Kristiansen. K., Pedersen. O., Parkhill. J., Weissenbach. J., Consortium. M., Bork. P., Ehrlich. SD. and Wang. J; A human gut microbial gene catalog established by deep metagenomic sequencing. Nature 464 (7285), 59-65 (2010)
  17. Yus, E., Maier, T., Michalodimitrakis, K., van Noort, V., Yamada, T., Chen, W.-H., Wodke, J. A. H., Guell, M., Martinez, S., Bourgeois, R., Kuhner, S., Raineri, E., Letunic, I., Kalinina, O. V., Rode, M., Herrmann, R., Gutierrez-Gallego, R., Russell, R. B., Gavin, A.-C., Bork, P., Serrano, L.; Impact of genome reduction on bacterial metabolism and its regulation. Science 326 (5957), 1263-1268 (2009)
  18. Kuhner, S., van Noort, V., Betts, M. J., Leo-Macias, A., Batisse, C., Rode, M., Yamada, T., Maier, T., Bader, S., Beltran-Alvarez, P., Castano-Diez, D., Chen, W.-H., Devos, D., Guell, M., Norambuena, T., Racke, I., Rybin, V., Schmidt, A., Yus, E., Aebersold, R., Herrmann, R., Bottcher, B., Frangakis, A. S., Russell, R. B., Serrano, L., Bork, P., Gavin, A.C.; Proteome organization in a genome-reduced bacterium. Science 326 (5957), 1235-1240 (2009).
  19. Guell, M., van Noort, V., Yus, E., Chen, W.-H., Leigh-Bell, J., Michalodimitrakis, K., Yamada, T., Arumugam, M., Doerks, T., Kuhner, S., Rode, M., Suyama, M., Schmidt, S., Gavin, A.-C., Bork, P., Serrano, L.; Transcriptome complexity in a genome-reduced bacterium. Science 326 (5957), 1268-1271 (2009).
  20. *Yamada T., Bork P.; Evolution of biomolecular networks - lessons from metabolic and protein interactions. Nat. Rev. Mol. Cell Biol. 10 (11):791-803 (2009).
  21. Gianoulis TA, Raes J, Patel PV, Bjornson R, Korbel JO, Letunic I, Yamada T, Paccanaro A, Jensen LJ, Snyder M, Bork P, Gerstein MB; Quantifying environmental adaptation of metabolic pathways in metagenomics. PNAS USA. 2009 Feb 3; 106(5): 1374-1379 (2009)

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