Department of Applied Molecular Biosciences

Division of Applied Biochemistry

LAB. OF BIOMACROMOLECULES

  FAX: +81-52-789-4120
Prof. YOSHIMURA, Tohru D. Agr. yosimura@
Assoc. Prof. HEMMI, Hisashi D. Eng. hhemmi@
Lecturer ITO, Tomokazu D. Agr. ito-t@
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The staff members of this laboratory are responsible for teaching basic courses of physical chemistry to undergraduate students. They are concerned mainly with experimental works in biochemistry and physical chemistry of macromolecules in solution with special regard to protein structure and function, as well as the interaction with various ligands. The research programs cover some of basic and applied areas related to biological and food science.

The projects now in progress are as follows;

  1. Study on metabolism and new functions of D-amino acids.
  2. Biochemistry of pyridoxal enzymes.
  3. Biochemistry and enzymology of isoprenoid biosynthesis in archaea.
  4. Metagenomic and biochemical analyses of fermentation processes.

Recent publications:

  1. Okuda K, Kato S, Ito T, Shiraki S, Kawase Y, Goto M, Kawashima S, Hemmi H, Fukada H, Yoshimura T (2015) Role of the aminotransferase domain in Bacillus subtilis GabR, a pyridoxal 5'-phosphate-dependent transcriptional regulator. Mol Microbiol, 95, 245-257.
  2. Ito T, Takada H, Isobe K, Suzuki M, Kitaura Y, Hemmi H, Matsuda T, Sasabe J, Yoshimura T (2015) PEGylated D-serine dehydratase as a D-serine reducing agent. J Pharm Biomed Anal, 116, 34-39.
  3. Takenaka T, Ito T, Miyahara I, Hemmi H, Yoshimura T (2015) A new member of MocR/GabR-type PLP-binding regulator of D-alanyl-D-alanine ligase in Brevibacillus brevis. FEBS J, 282, 4201-4217.
  4. Hattori A, Unno H, Goda S, Motoyama K, Yoshimura T, Hemmi H (2015) In vivo formation of the protein disulfide bond that enhances the thermostability of diphosphomevalonate decarboxylase, an intracellular enzyme from the hyperthermophilic archaeon Sulfolobus solfataricus. J Bacteriol, 197, 2463-3471.
  5. Mori T, Isobe K, Ogawa T, Yoshimura T, Hemmi H (2015) A phytoene desaturase homolog gene from the methanogenic archaeon Methanosarcina acetivorans is responsible for hydroxyarchaeol biosynthesis. Biochem Biophys Res Commun, 466, 186-191.
  6. Ito T, Matsuoka M, Koga K, Hemmi H, Yoshimura T (2014) Reaction mechanism of Zn2+-dependent D-serine dehydratase: role of a conserved tyrosine residue interacting with pyridine ring nitrogen of pyridoxal 5'-phosphate. J Biochem, 156, 173-180.
  7. Azami Y, Hattori A, Nishimura H, Kawaide H, Yoshimura T, Hemmi H (2014) (R)-mevalonate 3-phosphate is an intermediate of the mevalonate pathway in Thermoplasma acidophilum. J Biol Chem, 289, 15957-15967.
  8. Ogawa T, Isobe K, Mori T, Asakawa S, Yoshimura T, Hemmi H (2014) A novel geranylgeranyl reductase from the methanogenic archaeon Methanosarcina acetivorans displays unique regiospecificity. FEBS J, 281, 3165-3176.
  9. Isobe K, Ogawa T, Hirose K, Yokoi T, Yoshimura T, Hemmi H (2014) Geranylgeranyl reductase and ferredoxin from Methanosarcina acetivorans are required for the synthesis of fully reduced archaeal membrane lipid in Escherichia coli cells. J Bacteriol, 196, 417-423.
  10. Ito T, Iimori J, Takayama S, Moriyama A, Yamauchi A, Hemmi H, Yoshimura T (2013) Conserved pyridoxal protein that regulates Ile and Val metabolism. J Bacteriol, 195, 5439-5449.

LAB. OF MOLECULAR AND CELLULAR REGULATION

  FAX: +81-52-789-5542
Prof. MAKI, Masatoshi D. Agr. mmaki@
Assoc. Prof. SHIBATA, Hideki D. Sci. shibabou@
Asst. Prof. TAKAHARA, Terunao Ph. D. takahara@

The major interest in this laboratory is to understand how cellular functions such as signal transduction, membrane traffic, transport, growth and secretion are regulated in a Ca2+-dependent manner by biomolecular interactions of enzymes, receptors, adaptor proteins and other protein factors. Basic knowledge in biochemistry, cell biology and molecular biology is required.

Current projects are as follows:

  1. Cellular response to Ca2+ -stimulation by drugs, amino acids, cytokines etc.
  2. Structures, functions and ligand-recognition mechanisms of the penta-EF-hand Ca2+-binding protein ALG-2.
  3. Regulation of cell death by cellular factors in relation to Ca2+.
  4. Regulation of intracellular transport of macromolecules by Ca2+.

Recent publications:

  1. Analysis of limited proteolytic activity of calpain-7 using non-physiological substrates in mammalian cells. Maemoto Y, Kiso S, Shibata H, Maki M. FEBS J. 280(11):2594-607 (2013).
  2. Nuclear ALG-2 protein interacts with Ca2+ homeostasis endoplasmic reticulum protein (CHERP) Ca2+-dependently and participates in regulation of alternative splicing of inositol trisphosphate receptor type 1 (IP3R1) pre-mRNA. Sasaki-Osugi K, Imoto C, Takahara T, Shibata H, Maki M. J Biol Chem. 288(46):33361-3375 (2013).
  3. Involvement of calpain-7 in epidermal growth factor receptor degradation via the endosomal sorting pathway. Maemoto Y, Ono Y, Kiso S, Shibata H, Takahara T, Sorimachi H, Maki M.FEBS J. 281(16):3642-3655 (2014).
  4. A new role for annexin A11 in the early secretory pathway via stabilizing Sec31A protein at the endoplasmic reticulum exit sites (ERES). Shibata H, Kanadome T, Sugiura H, Yokoyama T, Yamamuro M, Moss SE, Maki M. J Biol Chem. 290(8):4981-93 (2015).
  5. Structural analysis of the complex between penta-EF-hand ALG-2 protein and Sec31A peptide reveals a novel target recognition mechanism of ALG-2. Takahashi T, Kojima K, Zhang W, Sasaki K, Ito M, Suzuki H, Kawasaki M, Wakatsuki S, Takahara T, Shibata H, Maki M. Int J Mol Sci. 16(2):3677-99 (2015).

LAB. OF MOLECULAR BIOREGULATION

Prof. MATSUDA, Tsukasa D. Agr., D.M.S. tmatsuda@
Assoc. Prof. NADANO, Daita D.M.S. nadano@
Asst. Prof. OHSHIMA, Kenji D. Agr. kenzi@
Des. Asst. Prof. MIYATA, Shinji D. Agr. smiyata@
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Ductal morphology constructed by mammary epithelial cells cultured on ECM coated porous membrane.

The aims of this laboratory are the elucidation of molecular mechanisms in regulation of biological systems in higher animals and plants useful in agriculture and biological industries.  In our laboratory a variety of biochemical, molecular- and cell-biological researches is ongoing on the biosynthesis, functions and dynamics of proteins, nucleic acids, and glycoconjugates in development, differentiation, reproduction, and immunity.  Goals of these researches are agricultural, industrial, and medical applications of biological products and systems.

The recent research projects are as follows:

  1. Functional interaction of intestinal epithelium and mucosal immune system with exogenous macromolecules and microbes.
  2. Biosynthesis and functional regulation of mammalian ribosomes.
  3. Molecular and cellular biology of reproductive organs and cells (mammary gland, ovary, and testis).
  4. Intercellular signaling networks mediated by exovesicles.

Recent publications:

  1. Yasueda T, Oshima K, Nakatani H, Tabuchi K, Nadano D, Matsuda T. A protective effect of milk fat globule EGF factor VIII (MFG-E8) on the spontaneous fusion of milk fat globules in breast milk. J Biochem., 158(1): 25-35, 2015.
  2. Nishio S, Kohno Y, Iwata Y, Arai M, Okumura H, Oshima K, Nadano D, Matsuda T. Glycosylated chicken ZP2 accumulates in the egg coat of immature oocytes and remains localized to the germinal disc region of mature eggs. Biol Reprod., 91(5): 107, 1-10, 2014.
  3. Oshima K, Yasueda T, Nishio S and Matsuda T, MFG-E8: Origin, Structure, Expression, Functions and Regulation, in "MFG-E8 and Inflammation", P. Wang (ed.), Springer, 2014, pp 1-31.
  4. Yonezawa, K., Sugihara, Y., Oshima, K., Matsuda, T., and Nadano, D. Lyar, a cell growth-regulating zinc finger protein, was identified to be associated with cytoplasmic ribosomes in male germ and cancer cells. Mol. Cell. Biochem., 395 (1-2): 221-229, 2014.
  5. Sugihara, Y., Sadohara, E., Yonezawa, K., Kugo, M., Oshima, K., Matsuda, T., and Nadano, D. Identification and expression of an autosomal paralogue of ribosomal protein S4, X-linked, in mice: Potential involvement of testis-specific ribosomal proteins in translation and spermatogenesis. Gene, 521 (1): 91-99, 2013.

LAB. OF NUTRITIONAL BIOCHEMISTRY

  Fax: +81-52-789-5050
Prof. SHIMOMURA, Yoshiharu D. Med. shimo@
Assoc. Prof. ODA, Hiroaki D. Agr. hirooda@
Lecturer KITAURA, Yasuyuki D. Agr. ykitaura@
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Microtubule network in spherical hepatocytes

The human health is closely related with the metabolic conditions, which is greatly affected by nutrition. In this lab, we are investigating the nutritional regulation of energy and protein-amino acid metabolism. It has been recently elucidated that branched-chain amino acids (BCAA) have great effects on the protein and glucose metabolism.

How can liver, a metabolic center organ, keep hepatocyte-phenotype? We have found that cultured hepatocytes with spherical cell shape can keep high levels of liver specific phenotype and that some liver-enriched transcription factors such as HNF-4. We are now focusing our effort on 1) identification of a regulatory transcription factors controlling HNF-4 by cell shape and 2) molecular mechanism of signal transduction pathway from cell shape to nucleus. Recently we are also trying to establish artificial liver support system by using spherical human hepatoma cells.

Current projects are follows:

  1. Nutritional regulation of gene expression in animals.
  2. Molecular mechanism of hepatocytes differentiation of 3-dimentional culture.
  3. Physiological significance of liver clock.
  4. Regulatory mechanism for the BCAA catabolism.
  5. Regulation of glucose metabolism by BCAA.

Current projects are follows:

  1. Zhen H, Nakamura K, Kitaura Y, Kadota Y, Ishikawa T, Kondo Y, Xu M, Shimomura Y. (2015) Regulation of the plasma amino acid profile by leucine via the system L amino acid transporter. Biosci Biotechnol Biochem. 79(12): 2057-2062.
  2. Kadota Y, Toyoda T, Hayashi-Kato M, Kitaura Y, Shimomura Y. (2015) Octanoic acid promotes branched-chain amino acid catabolism via the inhibition of hepatic branched-chain alpha-keto acid dehydrogenase kinase in rats. Metabolism 64: 1157-1164.
  3. Kitaura Y, Inoue K, Kato N, Matsushita N, Shimomura Y. (2015) Enhanced oleate uptake and lipotoxicity associated with laurate. FEBS Open Bio 5: 485-491.
  4. Yamada K, Aiba K, Kitaura K, Kondo Y, Nomura N, Nakamura Y, Fukushi D, Murayama K, Shimomura Y, Pitt J, Yamaguchi S, Yokochi K, Wakamatsu N.  (2015) Clinical, biochemical, and metabolic characterization of mild forms of human short-chain enoyl-CoA hydratase deficiency: significance of increased N-acetyl-S-(2-carboxypropyl)cysteine excretion. J Med Genet. 52(10): 691-698.
  5. Oda, H., Okuda, Y., Yoshida, Y., Kimura, N. and Kakinuma, A. (2015) Phenobarbital reduces blood glucose and gluconeogenesis through down-regulation of phosphoenolpyruvate carboxykinase (GTP) gene expression in rats. Biochem. Biophys. Res. Commun. 466, 306-311
  6. Chijimatsu, T., Umeki, M., Kataoka, Y., Kobayashi, S, Yamada, K., Oda, H. and Mochizuki, S. (2013) Lipid components prepared from a freshwater clam (Corbicula fluminea) extract ameliorate hypercholesterolemia in rats fed high-cholesterol diet. Food Chem. 136, 328-334.
  7. Yamajuku, D., Inagaki, T., Haruma, T., Okubo, S., Kataoka, Y., Kobayashi, S., Ikegami, K., Laurent, T., Kojima, T., Noutomi, K., Hashimoto, S. and Oda, H. (2012) Real-time monitoring in three-dimensional hepatocytes reveals that insulin acts as a synchronizer for liver clock. Scientific Rep. 2, 439; DOI:10.1038/srep00439
  8. Laurent, T., Murase, D., Tsukioka1, S., Matsuura, T., Nagamori, S. and Oda, H. (2012) A novel human hepatoma cell line, FLC-4, exhibits highly enhanced liver differentiation functions through the three-dimensional cell shape. J. Cell. Physiol. 227, 2898-2906.
  9. Yamajuku, D., Okubo, S., Haruma, T., Inagaki, T., Okuda, Y., Kojima T, Noutomi, K., Hashimoto, S. and Oda, H. (2009) Regular feeding plays an important role in cholesterol homeostasis through the liver circadian clock. Circulation Res.,105, 545-548.
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