Department of Bioengineering Sciences

Division of Biotechnology


  Fax: +81-52-789-5237
Assoc. Prof MATURANA, Andres Daniel Ph.D. maturana@
Lecturer NIIMI, Tomoaki D. Agr. tniimi@

Our team aims to develop biotechnology-based materials and devices for dedicating to human health, which are based on the molecular cell biological analyses of cell signaling mechanisms of humans and animals.

  1. Analysis of the functions of scaffold proteins-recruited signaling complexes in cardiac myocytes.
  2. Identification of the regulatory proteins or factors controlling the expression and activity of ion channels.
  3. Analysis of signal transduction mechanism for novel bone morphogenetic protein, NELL1.

Recent publications:

  1. Takahashi, K., Imai, A., Iijima, M., Yoshimoto, N., Maturana, A. D., Kuroda, S., and Niimi, T. (2015) Mapping the heparin-binding site of the osteoinductive protein NELL1 by site-directed mutagenesis. FEBS Lett. 589, 4026-4032.
  2. Ito, J., Iijima, M., Yoshimoto, N., Niimi, T., Kuroda, S., and Maturana, A. D. (2015) Scaffold protein Enigma Homolog activates CREB whereas a short splice variant prevents CREB activation in cardiomyocytes. Cell. Signal. 27, 2425-2433.
  3. Nakamura, Y., Hasebe, A., Takahashi, K., Iijima, M., Yoshimoto, N., Maturana, A.D., Ting, K., Kuroda, S. and Niimi, T. (2014) Oligomerization-induced conformational change in the C-terminal region of Nel-like molecule 1 (NELL1) protein is necessary for the efficient mediation of murine MC3T3-E1 cell adhesion and spreading. J. Biol. Chem., 289, 9781-9794.
  4. Kumazaki, K., Chiba, S., Takemoto, M., Furukawa, A., Nishiyama, K., Sugano, Y., Mori, T., Dohmae, N., Hirata, K., Nakada-Nakura, Y., Maturana, A.D., Tanaka, Y., Mori, H., Sugita, Y., Arisaka, F., Ito, K., Ishitani, R., Tsukazaki, T., and Nureki, O. (2014) Structural basis of Sec-independent membrane protein insertion by YidC. Nature, 509, 516-520.
  5. Takeda, H., Hattori, M., Nishizawa, T., Yamashita, K., Shah, S.T., Caffrey, M., Maturana, A.D., Ishitani, R., and Nureki, O. (2014) Structural basis for ion selectivity revealed by high-resolution crystal structure of Mg2+ channel MgtE. Nat. Commun., 5, 5374.
  6. Nishizawa, T., Kita, S, Maturana, A.D., Furuya, N., Hirata, K., Kasuya, G., Ogasawara, S., Dohmae, N., Iwamoto, T., Ishitani, R., and Nureki, O. (2013) Structural basis for counter-transport mechanism of H+/Ca2+ exchanger. Science, 341, 168-172.
  7. Ito, J., Takita, M., Takimoto, K., and Maturana, A.D. (2013) Enigma homolog 1 promotes myogenic gene expression and differentiation of C2C12 cells. Biochem. Biophys. Res. Commun., 435, 483-487.
  8. Tanaka, Y., Hipolito, C.J., Maturana, A.D., Ito, K., Kuroda, T., Higuchi, T., Katoh, T., Kato, H.E., Hattori, M., Kumazaki, K., Tsukazaki, T., Ishitani, R., Suga, H. and Nureki, O. (2013) Structural basis for the drug extrusion mechanism by a MATE multidrug transporter. Nature, 496, 247-251.
  9. Hasebe, A., Nakamura, Y., Tashima, H., Takahashi, K., Iijima, M., Yoshimoto, N., Ting, K., Kuroda, S., and Niimi, T. (2012) The C-terminal region of NELL1 mediates osteoblastic cell adhesion through integrin alpha3beta1. FEBS Lett., 586, 2500-2506.
  10. Ito, J., Hashimoto, T., Nakamura, S., Aita, Y., Yamazaki, T., Schlegel, W., Takimoto, K. and Maturana, A.D. (2012) Splicing transitions of the anchoring protein ENH during striated muscle development. Biochem. Biophys. Res. Commun., 421, 232-238.


  FAX: +81-52-789-4167
Prof. MORI, Hitoshi D. Agr. morihito@
  1. Regulation of Ethylene Biosynthesis
  2. Molecular Mechanism of Apical Dominance
Assoc. Prof. ITO, Masaki D. Sci. masakito@

Our group is studying basic and applied plant sciences, focusing on molecular aspects of plant growth and development. The goal of our study is to establish basic knowledge on how plants develop into defined shape and size, and to apply such knowledge for creation of plants with high productivity for food and biofuel. Following projects are currently under way.

  1. Regulatory mechanisms of ethylene production, a gaseous plant hormone, focusing on ACC synthase that acts as a key enzyme of its biosynthetic pathway.
  2. Studies on molecular mechanisms of parthenocarpic fruit development in tomato, by comparing parthenocarpic and non-parthenocarpic tomato varieties.
  3. Studies on hormonal control of apical dominance in pea.
  4. Studies on transcription factors that regulate cell division during development of Arabidopsis.
  5. Cell size control that is mediated by increase of cellular ploidy.

Recent publications:

  1. Goto, H., Okuda, S., Mizukami, A., Mori, H., Sasaki, N., Kurihara, D. and Higashiyama, T. (2011) Chemical Visualization of an Attractant Peptide, LURE. Plant Cell Physiol., 52, 49-58.
  2. Iwata, E., Ikeda, S., Matsunaga, S., Kurata, M., Yoshioka, Y., Criqui, M-C, Genschik, P. and Ito, M. (2011) GIGAS CELL1, a novel negative regulator of the anaphase-promoting complex/cyclosome, is required for proper mitotic progression and cell fate determination in Arabidopsis. Plant Cell, 23, 4382-4393.
  3. Haga, N., Kobayashi, K., Suzuki, T., Maeo, K., Kubo, M., Ohtani, M., Mitsuda, N., Demura, T., Nakamura, K., Jürgens, G., and Ito, M. (2011) Mutations in MYB3R1 and MYB3R4 cause pleiotropic developmental defects and preferential down-regulation of multiple G2/M-specific genes in Arabidopsis thaliana. Plant Physiol., 157, 706-17. 2011.
  4. Kamiyoshihara, Y., Iwata, M., Fukaya, T., Tatsuki, M. and Mori, H. (2010) Turnover of LeACS2, a wound-inducible 1-aminocyclopropane-1-carboxylic acid synthase in tomato, is regulated by phosphorylation/dephosphorylation. Plant J., 64, 140-150.
  5. Mori, H. (2010) Ethylene in “Plant Hormones, Comprehensive Natural Products Chemistry II”, 4. 02. 8, 87-90.
  6. Hirano, K., Asano, K., Tsuji, H., Kawamura, M., Mori, H., Kitano, H., Ueguchi-Tanaka, M. and Matsuoka, M. (2010) Characterization of the molecular mechanism underlying gibberellin perception complex formation in rice. Plant Cell, 22, 2680-2696.
  7. Hattori, Y., Nagai, K., Furukawa, S., Song, X-J., Kawano, R., Sakakibara, H., Wu, J., Matsumoto, T., Yoshimura, A., Kitano, H., Matsuoka, M., Mori, H. and Ashikari, M. (2009) The ethylene response factors SNORKEL1 and SNORKEL2 allow rice to adapt to deep water. Nature, 460, 1026-1030.
  8. Shimizu-Sato, S., Tanaka, M. and Mori, H. (2009) Auxin-cytokinin interactions in the control of shoot branching. Plant Mol. Biol., 69, 429-435.
  9. Kato, K., Gális, I., Suzuki, S., Araki, S., Demura, T., Criqui, M.C., Potuschak., T, Genschik, P., Fukuda, H., Matsuoka, K., and Ito, M. (2009) Preferential up-regulation of G2/M phase-specific genes by overexpression of the hyperactive form of NtmybA2 lacking its negative regulation domain in tobacco BY-2 cells. Plant Physiol., 149, 1945-1957.
  10. Ito-Inaba, Y., Hida, Y., Mori, H. and Inaba, T. (2008) Molecular identity of uncoupling proteins in thermogenic skunk cabbage. Plant Cell Physiol., 49, 1911-1916.
  11. Shimizu-Sato, S., Ike, Y. and Mori, H. (2008) PsRBR1 encodes a pea retinoblastoma-related protein that is phosphorylated in axillary buds during dormancy-to-growth transition. Plant Mol. Biol., 66, 125-135.
  12. Haga, N., Kato, K., Murase, M., Araki, S., Kubo, M., Demura, T., Suzuki, K., Müller, I., Voß, U., Jürgens, G. and Ito, M. (2007) R1R2R3-Myb proteins positively regulate cytokinesis through activation of KNOLLE transcription in Arabidopsis thaliana. Development, 134, 1101-1110.


  FAX: +81-52-789-4142
Prof. NAKANO, Hideo D. Eng. hnakano@
Assoc. Prof. IWASAKI, Yugo D. Agr. iwasaki@
Lecturer KOJIMA, Takaaki D. Agr. kojimat@
Asst. Prof. DAMNJANOVIC, Jasmina D. Agr. jasmina@

This laboratory is responsible for the undergraduate and graduate education in industrial biotechnology and biomolecular engineering. Our research focuses on engineering of functional proteins, such as enzymes and antibodies, enzymatic synthesis of bioactive compounds, as well as high-throughput screening of transcription factor binding sites in the genomes of microorganisms, plants and animals. In a quest for highly efficient and specific functional proteins, we utilize traditional protein engineering methods in combination with computational analysis of protein structure and dynamics, and our specialized technology for high-throughput screening of large random DNA-protein libraries.

The following research projects are currently in progress:

  1. Development and application of Beads display technology (coding DNA and corresponding protein are linked and displayed on the surface of the microbeads) for various purposes such as high throughput screening of random libraries in directed evolution of enzymes (horseradish peroxidase, manganese peroxidase, cytochrome P450, transglutaminase) and comprehensive analysis of transcription factor binding sites.
  2. Development of high-throughput screening system for monoclonal antibodies using single-cell RT-PCR and the cell-free protein synthesis (CFPS). Recently, we have succeeded in producing soluble and fully functional Fab fragments in E. coli CFPS system by fusing the Fab with Leucine zipper.
  3. Cloning, expression and protein engineering of lipid-modifying enzymes such as phospholipase D, lipase, and phosphatase to obtain enzymes with novel functions or improved activities.
  4. Efficient enzymatic synthesis of bioactive lipids with defined chemical structure, such as phosphatidylinositol and phosphatidyl-1-glucose.
  5. Genome-wide identification of genes regulated by transcription factors (TFs) from various organisms, such as fungi, plants and insects, by a combinatorial analysis using genomic systematic evolution of ligands by exponential enrichment (gSELEX)-Seq, RNA-Seq and bioinformatics.

Recent publications:(2015 - , former publications are listed on

  1. Damnjanovic, J., Kuroiwa, C., Tanaka, H., Ishida, K., Nakano, H., and Iwasaki, Y. (2016) Directing positional specificity in enzymatic synthesis of bioactive 1-phosphatidylinositol by protein engineering of a phospholipase D. Biotechnol. Bioeng. 113, 62-71.
  2. DeKosky, B. J., Kojima, T., Rodin, A., Charab, W., Ippolito, G., Ellington, A. D., and Georgiou, G. (2015) In-Depth Determination and Analysis of the Human Paired Heavy and Light Chain Antibody Repertoire. Nat. Med. 21, 86-91.
  3. Mori, A., Hara, S., Sugahara, T., Kojima, T., Iwasaki, Y., Kawarasaki, Y., Sahara, T, Ohgiya, S., and Nakano, H. (2015) Signal peptide optimization tool for the secretion of recombinant protein from Saccharomyces cerevisiae. J. Biosci. Bioeng. 120, 518-525
  4. Zhu, B., Mizoguchi, T., Kojima, T., and Nakano, H. (2015) Ultra-High-Throughput Screening of an In Vitro-Synthesized Horseradish Peroxidase Displayed on Microbeads Using Cell Sorter. PLoS One 10, e0127479
  5. Kojima, T., Mizoguchi, T., Ota, E., Hata, J., Homma, K., Zhu, B., Hitomi, K., and Nakano, H. (2015) Immobilization of proteins onto microbeads using a DNA binding tag for enzymatic assays. J. Biosci. Bioeng. in press.
  6. Ujiie, A., Nakano, H., and Iwasaki, Y. (2015) Extracellular production of Pseudozyma (Candida) antarctica lipase B with genuine primary sequence in recombinant Escherichia coli. J. Biosci. Bioeng. in press
  7. Murzabaev, M., Kojima, T., Mizoguchi, T., Kobayashi, I., DeKosky, B. J., Georgiou, G., and Nakano, H. (2015) Handmade microfluidic device for biochemical applications in emulsion. J. Biosci. Bioeng. in press
  8. Ojima-Kato, T., Hashimura, D., Kojima, T., Minabe, S., and Nakano, H. (2015) In vitro generation of rabbit anti- Listeria monocytogenes monoclonal antibody using single cell based RT-PCR linked cell-free expression systems. J. Immunol. Methods, 427, 58-65


  FAX: +81-52-789-4072
Prof. TSUKAMURA, Hiroko D. Agr. htsukamu@
Assoc. Prof. UENOYAMA, Yoshihisa D. Agr. uenoyama@
Lecturer INOUE, Naoko D. Agr. ninoue@
Des. Asst. Prof. SUNANO, Yui D. Agr. sunano@
Des. Asst. Prof. SKOLDING, Nicola Stephanie D. Agr. nicola@
Kisspeptin, a product of Kiss1 gene, plays a key role in regulating reproductive function in mammals. The image shows an epigenetic regulation of hypothalamic Kiss1 gene expressions induced by estrogen from mature follicles. Preovulatory level of estrogen induces histone acetylation in the Kiss1 promoter region, resulting in an increase in Kiss1 expression, and consequently induces gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) surge and then ovulation.

The laboratory is carrying out studies on neuroendocrine control of reproductive phenomena, such as puberty, estrous cycle, pregnancy, lactation, and sexual differentiation of the brain, focusing on the role of kisspeptin in regulating hypothalamo-pituitary-gonadal axis.

Recent publications:

  1. Uenoyama, Y., Tanaka, A., Takase, K., Yamada, S., Pheng, V., Inoue, N., Maeda, K.I., Tsukamura, H. (2015) Central estrogen action sites involved in prepubertal restraint of pulsatile luteinizing hormone release in female rats. J Reprod Dev 61: 351-359.
  2. Minabe S, Deura C, Ikegami K, Goto T, Sanbo M, Hirabayashi M, Inoue N, Uenoyama Y, Maeda KI, Tsukamura H (2015) Pharmacological and morphological evidence of AMPK-mediated energy sensing in the lower brain stem ependymocytes to control reproduction in female rodents. Endocrinology 156: 2278-2287.
  3. Uenoyama Y, Nakamura S, Hayakawa Y, Ikegami K, Watanabe Y, Deura C, Minabe S, Tomikawa J, Goto T, Ieda N, Inoue N, Sanbo M, Tamura C, Hirabayashi M, Maeda KI, Tsukamura H. (2015) Lack of Pulse and Surge Modes and Glutamatergic Stimulation of LH Release in Kiss1 Knockout Rats. J Neuroendocrinol 27:187-197.
  4. Watanabe Y, Uenoyama Y, Suzuki J, Takase K, Suetomi Y, Ohkura S, Inoue N, Maeda KI, Tsukamura H. (2014) Oestrogen-Induced Activation of Preoptic Kisspeptin Neurones May be Involved In the Luteinizing Hormone Surge in Male and Female Japanese Monkeys. J Neuroendocrinol 26: 909-917.
  5. Goto T, Tomikawa J, Ikegami K, Minabe S, Abe H, Fukanuma T, Imamura T, Takase K, Sanbo M, Tomita K, Hirabayashi M, Maeda KI, Tsukamura H, Uenoyama Y. (2014) Identification of hypothalamic arcuate nucleus-specific enhancer region of Kiss1 gene in mice. Mol Endocrinol 29:121-129.
  6. Ieda N, Uenoyama Y, Tajima Y, Nakata T, Kano M, Naniwa Y, Watanabe Y, Minabe S, Tomikawa J, Inoue N, Matsuda F, Ohkura S, Maeda KI, Tsukamura H. (2014) KISS1 gene expression in the developing brain of female pigs in pre- and peripubertal periods. J Reprod Dev 60 (4):312-316.
  7. Sakakibara M, Uenoyama Y, Minabe S, Watanabe Y, Deura C, Nakamura S, Suzuki G, Maeda KI and Tsukamura H. (2013) Microarray analysis of perinatal-estrogen-induced changes in gene expression related to brain sexual differentiation in mice. PLoS ONE 8(11): e79437.
  8. Nakahara T, Uenoyama Y, Iwase A, Oishi S, Nakamura S, Minabe S, Watanabe Y, Deura C, Noguchi T, Fujii N, Kikkawa F, Maeda KI, Tsukamura H. (2013) Chronic peripheral administration of kappa-opioid receptor antagonist advances puberty onset associated with acceleration of pulsatile luteinizing hormone secretion in female rats. J Reprod Dev 59: 479-484.
  9. Tomikawa J, Uenoyama Y, Ozawa M, Fukanuma T, Takase K, Goto T, Abe H, Ieda N, Minabe S, Deura C, Inoue N, Sanbo M, Tomita K, Hirabayashi M, Tanaka S, Imamura T, Okamura H, Maeda KI, Tsukamura H (2012) Epigenetic regulation of Kiss1 gene expression mediating estrogen-positive feedback action in the mouse brain. Proc Natl Acad Sci U S A. 109(20):E1294-301.
  10. Inoue N, Sasagawa K, Ikai K, Sasaki Y, Tomikawa J, Oishi S, Fujii N, Uenoyama Y, Ohmori Y, Yamamoto N, Hondo E, Maeda K and Tsukamura H (2011) Kisspeptin neurons mediate reflex ovulation in the musk shrew (Suncus murinus). Proc Natl Acad Sci U S A 108:17527-32.