Department of Applied Molecular Biosciences

Division of Biomodelling

LAB. OF MOLECULAR FUNCTION MODELING

Photo3-1-1
From upper left (clockwise): a myxobacterium producing novel antibiotics; phytopathogen sexual spores induced by a mating hormone α1; bioluminescent crustacean Cypridina hilgendorfii; Japanese firefly Luciola cruciata.

Biological phenomena in nature are mainly regulated by the interaction between small organic molecules (hormones, toxins, antibiotics, etc.) and biopolymers (receptor proteins, enzymes, etc.) like the relation of key to keyhole. Our laboratory focuses on both the exogenous and endogenous factors responsible for particular biological events; the former includes antibiotic, antitumor and toxic actions, and enzyme inhibition, whereas the latter includes bioluminescence, symbiosis, hormonal action, and food chains. We are trying not only to discover novel biologically important substances but also to unveil the molecular mechanisms behind the phenomena by modeling their molecules and functions.

Organic chemistry, biochemistry, and molecular biology are fundamental knowledge in our research fields.

  1. Antibiotics, antitumor substances, anti-aging substances, neuritogenic substances, and fungal hormones. These bioactive compounds, which have been searched from microorganisms (myxobacteria, etc.) and marine organisms (sponges, etc.) using suitable bioassay systems, could be useful as medical and agrochemical seeds. The identification of their target biomolecules and interactions are also important subjects.
  2. Bioluminescence emerged independently on several occasions, yet the evolutionary origins remain obscure. For inferring the evolution of the bioluminescence phenomena, we are focusing on discovering of key molecules and the biosynthetic pathways, by comparison of homologous genes of the key enzymes, molecular phylogenetic analysis, and homology modeling study.

Recent Publications:

  1. Ojika M, Kigoshi H, Suenaga K, Imamura Y, Yoshikawa K, Ishigaki T, Sakakura A, Mutou T, Yamada K. (2012) Aplyronines D-H from the sea hare Aplysia kurodai : isolation, structures, and cytotoxicity. Tetrahedron, 68, 982-987
  2. Molli SD, Qi J, Yajima A, Shikai K, Imaoka T, Nukada T, Yabuta G, Ojika M. (2012) Structure-activity relationship of α hormones, the mating factors of phytopathogen Phytophthora. Bioorg. Med. Chem. 20, 681-686.
  3. Govindam SV, Yoshioka Y, Kanamoto A, Fujiwara T, Okamoto T, Ojika M. (2012) Cyclolobatriene, a novel prenylated germacrene diterpene, from the soft coral Lobophytum pauciflorum. Bioorg. Med. Chem. 20, 687-692.
  4. Oba, Y.,Yoshida M., Shintani T.,Funahashi M., Inoue S.(2012) Firefly Luciferase genes from the subfamilies Psiolocladinae and Ototretinae (Lampyridae, Coleoptera). Comp. Biochem. Physiol. B 161, 110-116.
  5. Ojika M, Molli SD, Kanazawa H, Yajima A, Toda K, Nukada T, Mao H, Murata R, Asano T, Qi J, Sakagami Y. (2011) The second Phytophthora mating hormone defines interspecies biosynthetic crosstalk. Nat. Chem. Biol. 7, 591-593.
  6. Oba Y, Mori N, Yoshida M, Inouye S. (2010) Identification and characterization of a luciferase isotype in the Japanese firefly, Luciola cruciata, involving in the dim glow of firefly egg. Biochemistry, 49, 10788-10795

LAB. OF GENOME AND EPIGENOME DYNAMICS

Prof. ICHIYANAGI, Kenji D. Sci. ichiyana@

Our research interests are epigenetic regulation during mammalian development, roles for epigenetic and genetic diversities in evolution, and roles for retrotransposons in regulation of the genome function.

Current research projects:

  1. Epigenetic regulation of genes and retrotransposons by DNA methylation, histone modifications, and small RNAs during mammalian germ cell development.
  2. The mode and mechanism of epigenetic reprograming in germ cells.
  3. Epigenetic regulation of meiotic recombination.
  4. Comparison of epigenetic states (epigenomes) between close related species (e.g., human, chimpanzee, gorilla, orangutan, and macaques) and between sub-species (e.g., mouse strains of different sub-species origin).
  5. Chromatin boundary function of SINE retrotransposons.
  6. Retrotransposon-driven transcription to generate gene expression diversity.

Recent publications:

  1. Ichiyanagi T, Ichiyanagi K, Ogawa A, Kuramochi-Miyagawa S, Nakano T, Chuma S, Sasaki H, and Udono H. (2014) HSP90α plays an important role in piRNA biogenesis and retrotransposon repression in mouse. Nucleic Acids Res 42, 11903-11911
  2. Fukuda K, Ichiyanagi K, Yamada Y, Go Y, Udono T, Wada S, Maeda M, Soejima H, Saitou N, Ito T, and Sasaki H. (2013) DNA methylation differences between humans and chimpanzees are associated with genetic changes, transcriptional divergence and disease genes. J Hum Genet 58:446-454
  3. Ichiyanagi T, Ichiyanagi K, Miyake M, and Sasaki H. (2013) Accumulation and loss of non-CpG methylation during male germ-cell development. Nucleic Acids Res 41, 738-745
  4. Ichiyanagi K. (2013) Epigenetic regulation of transcription and possible functions of mammalian short interspersed elements, SINEs. Genes Genet Syst 88, 19-29
  5. Ichiyanagi K. (2012) Inhibition of MspI cleavage activity by hydroxymethylation of the CpG site: A concern for DNA modification studies using restriction endonucleases. Epigenetics 7, 131-136
  6. Ichiyanagi K, Li Y, Watanabe T, Ichiyanagi T, Fukuda K, Kitayama J, Yamamoto Y, Kuramochi-Miyagawa S, Nakano T, Yabuta Y, Seki Y, Saitou M, and Sasaki H. (2011) Locus- and domain-dependent control of DNA methylation at mouse B1 retrotransposons during male germ cell development. Genome Res 21, 2058-2066
  7. Ichiyanagi K, Nakajima R, Kajikawa M, and Okada N. (2007) Novel retrotransposon analysis reveals multiple mobility pathways dictated by hosts. Genome Res17, 33-41

LAB. OF CHEMICAL BIOLOGY OF NATURAL PRODUCTS

  Fax: +81-52-789-4284
Prof. KITA, Masaki D. Sci. mkita@

The principal research objectives of this lab are to investigate diverse natural products that regulate biologically and physiologically intriguing phenomena on the basis of organic and biological organic chemistry. Our research interest is also extended to chemical biology, such as study on the target molecules and mode of actions of bioactive natural products by using their chemical probes.

The following studies are currently in progress:

  1. Isolation, structure determination, synthesis, and modes of action of bioactive natural products that regulate biologically and physiologically intriguing phenomena.
  2. Anesthetic substances from venomous mammals, and key substances for marine symbiotic relationships.
  3. Development of new analytical methods for target molecules using fluorescent probes.

Recent publications:

  1. Yoneda, K.; Hu, Y.; Watanabe, R.; Kita, M.; Kigoshi, H. Binding Position Analysis of Target Proteins with the Use of Amidopyrene Probes as LA-LDI Enhancing Tags. Org. Biomol. Chem. 2016, 14, 8564-8569.
  2. Kita, M.; Oka, H.; Usui, A.; Ishitsuka, T.; Mogi, Y.; Watanabe, H.; Tsunoda, M.; Kigoshi, H. Total Synthesis of Mycalolides A and B Through Olefin Metathesis. Angew. Chem. Int. Ed. 2015, 54, 14174-14178.
  3. Kawamura, A.; Kita, M.; Kigoshi, H. Aplysiasecosterol A: A 9,11-Secosteroid with An Unprecedented Tricyclic gamma-Diketone Structure from the Sea Hare Aplysia kurodai. Angew. Chem. Int. Ed. 2015, 54, 7073-7076.
  4. Kita, M.; Kigoshi, H. Marine Natural Products That Regulate Multiple Cytoskeletal Protein Interactions. Nat. Prod. Rep. 2015, 32, 534-542.
  5. Kita, M.; Hirayama, Y.; Yoneda, K.; Yamagishi, K.; Chinen, T.; Usui, T.; Sumiya, E.; Uesugi, M.; Kigoshi, H. Inhibition of Microtubule Assembly by A Complex of Actin and Antitumor Macrolide Aplyronine A. J. Am. Chem. Soc. 2013, 135, 18089-18095.
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