KAKENHI (Grants-in-Aid for Scientific Research) -
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Grant number：24K01635 2024.4 - 2027.3
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
Authorship：Principal investigator Grant type：Competitive
Grant amount：\18590000 （ Direct Cost: \14300000 、 Indirect Cost：\4290000 ）
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Grant number：23H03823 2023.4 - 2026.3
日本学術振興会 科学研究費助成事業 学術変革領域研究(B)
恒松 雄太, 酒井 隆一, 北 将樹, 犬塚 俊康
Authorship：Coinvestigator(s) Grant type：Competitive
天然有機化合物(天然物)は各々の生物種に備えられた特殊な代謝機構を介して生合成される物質である。化学構造的多様性が高く、歴史的には医薬品開発の探索源などとして利用されてきた。その一方、実環境に目を移すと、各生産生物がどのような意図で天然物産生を行っているのか?産生された物質の生態における生理的機能や役割は何か?といった根本的な問いについては理解が進んでいない。そこで本研究ではサンゴ-褐虫藻-細菌叢間の共生系に着目し、これら生物間において相互作用に働く鍵物質を同定する。「物質を介して生態系を俯瞰する」という新しい観点を基にした生物圏の生態情報と物質機能情報を紐付ける新たな研究手法を確立する。
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Chemical Evolutionary Ecology Studies on the Repellent Substances from Shrews
Grant number：20K21270 2020.7 - 2022.3
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Research (Exploratory)
KITA Masaki
Authorship：Principal investigator Grant type：Competitive
Grant amount：\6500000 （ Direct Cost: \5000000 、 Indirect Cost：\1500000 ）
Shrews are unique mammals that have poisons in saliva, and it has been suggested that their muscle tissue contain insect repellent substances, and the odor glands contain odorants that repel large mammals. In this study, we aimed to discover novel functional substances related to predation derived from shrews, and to understand their roles in evolution. The enzymatic activity of salivary gland extracts were evaluated, and we established the presence of several serine proteases related to blood coagulation, such as kallikrein, plasmin, and thrombin. In addition, the volatile components contained in the odor grands were analyzed by GC-MS or other methods, and a macrolactone known as a musk odor substance was identified. In the future, we will synthesize the identified compounds, confirm their activities, and elucidate their physiological functions.
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Chemical Communication on the Mammalian Venom
Grant number：20H04770 2020.4 - 2022.3
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
Authorship：Principal investigator Grant type：Competitive
Grant amount：\4940000 （ Direct Cost: \3800000 、 Indirect Cost：\1140000 ）
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Grant number：20H04703 2020.4 - 2022.3
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
Authorship：Principal investigator Grant type：Competitive
Grant amount：\4940000 （ Direct Cost: \3800000 、 Indirect Cost：\1140000 ）
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Analysis of cellular machinery using PPI-inducing small molecules
Grant number：19H02839 2019.4 - 2022.3
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
KITA Masaki
Authorship：Principal investigator
Grant amount：\17550000 （ Direct Cost: \13500000 、 Indirect Cost：\4050000 ）
We focused on the natural ligands that interact with actin, and aimed to identify new protein-protein interaction (PPI) functional points that could become the targets for drug discovery, and to elucidate the moving machinery associated with the cytoskeleton. We synthesized structurally-simplified actin-binding derivatives of the antitumor natural product aprilonin A (ApA), which induces unique PPI between actin and tubulin to inhibit microtubule dynamics. Using this compounds, we successfully affinity-purified cytoskeletal actin from cell lysate. In addition, molecular docking simulation and molecular dynamics studies succeeded in constructing a possible model of the actin-ApA-tubulin ternary complex in which the C7 TMSer ester interacted with tubulin, which is important for the potent cytotoxicity of ApA.
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Chemical communication of venomous mammals
Grant number：18H04613 2018.4 - 2020.3
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
Authorship：Principal investigator
Grant amount：\5200000 （ Direct Cost: \4000000 、 Indirect Cost：\1200000 ）
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Ecological and chemical surveys of endangered wildlife species endemic to the Caribbean region
Grant number：16H05655 2016.4 - 2020.3
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
KITA MASAKI
Authorship：Principal investigator
Grant amount：\13650000 （ Direct Cost: \10500000 、 Indirect Cost：\3150000 ）
We examined chemical ecological survey on Caribbean wild animals and plants, including an endangered mammal Cuban solenodon and local medicinal plants. Field surveys were conducted for a total of 140 days in the Republic of Cuba and the Dominican Republic, but solenodon was not captured. However, we have elucidated the evolutionary position of Cuban solenodon using DNA samples from individuals captured in previous studies, and newly found the anti-inflammatory effect of jacaranone isolated from the medicinal plant Jacaranda sp.
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Grant number：15H02503 2015.4 - 2018.3
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)
Kanaho Yasunori, FUJII Ikuo, KITA Masaki, FUNAKOSHI Yuji, YAMAUCHI Yohei, MIURA Yuki, MIYACHI Taito, Lin Yueh-Chen, Van Ngo Thai Bich, Tsai Meng-Tsz, FUJIWARA Daisuke, Tito Akindele, YONEDA kozou, YAMAGISHI kota
Authorship：Collaborating Investigator(s) (not designated on Grant-in-Aid)
In this project, it was confirmed that the small G protein Arf6 positively regulates both tumor growth and invasion of cancer cells, and screened peptides inhibiting Arf6 activation to develop a novel anti-cancer drug. It was found that Arf6-specific GTPase-activating protein ARAP3 regulates invadopodia formation through inactivation of Arf6 in cancer cells, and that Arf6 expressed in lymphatic endothelial cells regulates tumor growth. These results demonstrate that Arf6 regulates both tumor growth and invasion/metastasis of cancer cells, and indicate that Arf6 is a candidate for developing a novel anti-cancer drug. When peptides inhibiting Arf6 activation were screened using the peptide library with about 35 amino acid residues, one peptide specifically inhibited Arf6 activation. Thus, a drug lead peptide for a novel anti-cancer drug development was successfully found.
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光親和性プローブとLA-LDI-MSを用いた標的生体分子の結合部位解析法の開発
2015.4 - 2017.3
科学研究費補助金 挑戦的萌芽研究
北 将樹
Authorship：Principal investigator
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Development of the binding position analysis of target biomolecules by using photoaffinity probes and LA-LDI MS
Grant number：15K12753 2015.4 - 2017.3
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research
KITA Masaki
To establish new binding mode analysis methods of target biomacromolecules, we aimed to develop photoaffinity probes that can covalently bind to target molecules and efficiently analyze their fragment peptides by using label-assisted laser desorption/ionization mass spectrometry (LA-LDI MS). We found that 6-amidopyrene (apy) derivatives were highly detectable by the LDI MS instrument. An apy-conjugated photoaffinity derivative of an antitumor natural product, aplyronine A, was then synthesized. By the irradiation of UV light (365 nm), this probe efficiently photoreacted with solvent molecules and form covalent bonds. Furthermore, actin was quantitatively labeled with an apy NHS ester probe of aplyronine A, and the sequence of an apy-labeled peptide was established by MS/MS analysis.
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Study on Protein-Protein Interaction Induced by Marine Natural Products
Grant number：26242073 2014.6 - 2019.3
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)
Kigoshi Hideo
Authorship：Coinvestigator(s)
Marine macrolide, aplyronine A exhibits extremely strong antitumor activity by inducing protein-protein interaction (PPI) between two major cytoskeletons, actin and tubulin. In this study, we aimed to clarify structural factors for PPI and to develop the artificial analogs. Because the side-chain moiety binds to actin and the trimethylserine moiety in the macrolactone moiety interacts with tubulin, we design two hybrids from aplyronine A and the other actin-deplymerizing marine macrolides. Among them, hybrid from alyronine A and swinholide A shows same biological activity as aplyronine A, which is a simplified analog of aplyronine A.
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2014.6 - 2017.3
科学研究費補助金 基盤研究(A)
木越 英夫
Authorship：Coinvestigator(s)
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2014.4 - 2016.3
科学研究費補助金 新学術領域研究
木越 英夫
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陸棲哺乳類の産生する麻痺性神経毒およびプロテアーゼの構造と機能
2013.4 - 2016.3
科学研究費補助金 若手研究(A)
北 将樹
Authorship：Principal investigator
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2011.11 - 2014.3
科学研究費補助金 基盤研究(B)
木越 英夫
Authorship：Coinvestigator(s)
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2009.4 - 2013.3
科学研究費補助金 若手研究(A)
北 将樹
Authorship：Principal investigator
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2009.4 - 2012.3
科学研究費補助金 挑戦的萌芽研究
北 将樹
Authorship：Principal investigator
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抗腫瘍性などの生物活性を有する海洋天然物の新型作用機序の解明
2008.4 - 2011.3
科学研究費補助金 基盤研究(B)
木越 英夫
Authorship：Coinvestigator(s)
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2005.4 - 2007.3
科学研究費補助金 若手研究(B)
北 将樹
Authorship：Principal investigator