酸素呼吸は生命活動のエネルギーを得るために不可欠ですが、同時に細胞にとって有害な活性酸素を作り出します。また、生体の機能に一定の確率でエラーが起こることも避けられません。その他にも、紫外線、けが、細菌による感染など生命機能に障害を与えるさまざまな外部要因が存在します。このような障害やエラーは時間とともに確実に増大し、老化を早める要因になると考えられます。生物には、これらの老化促進要因に対抗するしくみが存在します。障害の発生要因を除去したり、エラーが発生したときに速やかに修復したり、あるいは重度の障害をうけた細胞をアポトーシス（細胞死）によって排除するしくみは代表的なものです。このような生命の危機管理システムに関わる遺伝子は老化抑制遺伝子とよぶことができます。酸化ストレスに抵抗性を示す突然変異体を分離して、その原因遺伝子をつきとめ、その性質を明らかにする研究を行っています。

＜本能行動の神経遺伝学＞　遺伝的発生過程に特段の異常はないのに、成虫の様々な行動（性行動、睡眠リズム、社会性行動、摂食行動など）が異常になる変異体を多数分離して、その原因遺伝子をつきとめ、本能行動を制御する脳神経回路やその動作原理を明らかにする研究を行っています。分子生物学，行動解析，脳イメージング解析などさまざまな実験技術を駆使して研究を進めています。

＜失恋の記憶を探る＞　行動を利用すると動物の記憶を測定することができます。我々の研究室ではショウジョウバエの失恋の記憶を利用し、長期間保持される記憶（長期記憶）を獲得するために必須な遺伝子の探索を行なっています。
動物の概日リズムを制御する時計遺伝子periodが長期間持続する記憶を形成するために必須であることをこれまでに見出しました。現在，長期記憶形成におけるperiodの分子機能を明らかにする研究を進めています。

＜光環境が記憶に及ぼす影響＞　ヒトもハエも昼行性の動物です。私達は光がハエの長期記憶にどのような影響を与えるのか，またそのメカニズムを明らかにする研究を進めています。

＜磁気遺伝学ツールの開発＞
　神経細胞の活動を光や温度で制御する技術（光遺伝学，温度遺伝学）が近年開発され，脳機能研究に利用されています。私達は磁石を使って神経を活性化したり抑制したりできるツールの開発を目指しています。

＜フェロモン受容のバーチャルリアリティモデル＞
　ハエでは，オスの求愛を抑制するフェロモンが知られています。このフェロモンをオスが嗅ぐとあまりメスに求愛しなくなります。温度遺伝学や光遺伝学を利用して，フェロモンを嗅いでいないのに，嗅いだような状態を作りだし，その結果脳機能にどのような変化が生じるのかを明らかにする研究を開始しています。

個々の遺伝子の機能だけでなく、ショウジョウバエの14,000個の遺伝子を収めているゲノム全体を相手にした研究を行っています。たとえば、突然変異体を大規模に作製するための方法を開発しています。それによって、個々の遺伝子の研究を効率化できるだけでなく、機能的に関連する複数の遺伝子の関係を解析するのに役立ちます。また、高等生物のゲノムの特徴として、遺伝子の数を大幅に上回る種類のタンパク質を作り出すいくつかのしくみが存在します。中でも，選択的スプライシングは、一つの遺伝子から多数の異なるタンパク質を作り出すしくみとして、神経系を初めとする多細胞生物の複雑な生命機能の進化と密接に関わっているものと考えられています。選択的スプライシングを制御するしくみと、その結果生じる産物の機能的多様性を解析する研究を行っています。

ショウジョウバエを使って記憶と学習にかかわる分子機構の研究をしています。100匹のハエを実験装置に入れてニオイAを嗅がせ同時に電気ショックを与えた後、刺激を与えずにニオイBを嗅がせます。その後ニオイA、Bを同時に嗅がせ、どちらに移動するかを調べ、ハエの学習と記憶がどれだけ保持されるかを測定します。ヒトと同じようにハエも加齢によって記憶力が低下しますが、こうした記憶力低下が起こらない変異体を見つけ、記憶力低下の原因となる遺伝子を発見しました。またこの変異体の研究から、脳内には記憶を積極的に抑える機構の存在を提唱しています。そこに関わるタンパク質や遺伝子を発見し、この機構の全体像を解明することが今の課題です。それが解明できれば、将来的には疾患などにより起こる記憶障害の治療にも役立つと考えています。首都大学東京はショウジョウバエの研究に優れた環境が整っており、これらを充分に活用し、戦略研究センターでの研究活動を進めて行きたいと考えています。

関連情報

最近の研究業績

1. Inami S, Sato S, Kondo S, Tanimoto H, Kitamoto T, and *Sakai T. (2020) Environmental light is required for maintenance of long-term memory in Drosophila. J Neurosci (in press)
2. Sato S, Ueno K, Saitoe M, and *Sakai T. (2018) Synaptic depression induced by postsynaptic cAMP production in the Drosophila mushroom body calyx. J. Physiol. 596 (12) 2447-2461.
3. Ohashi H, and *Sakai T. (2018) Leucokinin signaling pathway regulates hunger-driven reduction of behavioral responses to noxious heat in Drosophila. Biochem. Biophys. Res. Commun. 499: 221-226
4. Watanabe K, Suzuki Y, Inami S, Ohashi H, and *Sakai T. (2018) Light is required for proper female mate choice between winged and wingless males in Drosophila. Genes and Genetic System 93(3):119-123.
5. Shimada N1, Inami S1, Sato S, Kitamoto S, and *Sakai T. (2016) Modulation of light-driven arousal by LIM-homeodomain transcription factor Apterous in large PDF-positive lateral neurons of the Drosophila brain. Scientific Rep. 6: 37255 (1 These authors contributed equally to this work.)
6. Mabuchi I1,Shimada N1, Sato S, Ienaga K, Inami S, and *Sakai T　(2016) Mushroom body signaling is required for locomotor activity rhythms in Drosophila. Neurosci. Res. 111: 25-33. (1 These authors contributed equally to this work.)
7. Watanabe, K. and *Sakai, T. (2015) Knockout mutations of insulin-like peptides enhance sexual receptivity in Drosophila virgin females. Genes and Genetic System (in press)
8. Ohashi, H. and *Sakai, T. (2015) Novel behavioral assay of wasabi avoidance in Drosophila using a video tracking system. Appl. Entmol. Zool. 50: 137-142.
9. Sato, S., Kitamoto, T. and *Sakai, T. (2014) Modulation of innate and learned sexual behaviors by the TRP channel Painless expressed in the fruit fly brain: behavioral genetic analysis and its implications. Front. Behav. Neurosci. 8: Article 400 (doi: 10.3389/fnbeh.2014.00400)
10. *Sakai, T., Watanabe, K., Ohashi, H., Sato, S., Inami, S., Shimada, N., Kitamoto, T. (2014) Insulin-producing cells regulate the sexual receptivity through the Painless TRP channel in Drosophila virgin females. PLoS ONE 9(2): e88175
11. Amano A, Tsunoda M, Aigaki T, Maruyama N, Ishigami A. (2013) Effect of ascorbic acid deficiency on catecholamine synthesis in adrenal glands of SMP30/GNL knockout mice. Eur J Nutr. In Press.
12. Trindade LS, Aigaki T, Peixoto AA, Balduino A, Mânica da Cruz IB, Heddle JG. (2013) A novel classification system for evolutionary aging theories. Front Genet. 4:25.
13. Cheng Z, Tsuda M, Kishita Y, Sato Y, Aigaki T. (2013) Impaired energy metabolism in a Drosophila model of mitochondrial aconitase deficiency. Biochem Biophys Res Commun. 433, 145-150.
14. Aizawa S, Senda M, Harada A, Maruyama N, Ishida T, Aigaki T, Ishigami A, Senda T. (2013) Structural basis of the γ-lactone-ring formation in ascorbic acid biosynthesis by the senescence marker protein-30/gluconolactonase. PLoS One. 8, e53706.
15. Kadengodlu PA, Aigaki T, Abe H, Ito Y. (2013) Cationic cholesterol-modified gelatin as an in vitro siRNA delivery vehicle. Mol Biosyst. 9, 965-968.
16. Sakai, T., Sato, S., Ishimoto, H., *Kitamoto, T. (2013) Significance of the centrally expressed TRP channel Painless in Drosophila courtship memory. Learning & Memory 20: 34-40.
17. Asano T., Taoka M., Shinkawa T., Yamauchi Y., Isobe T., Sato D.（2013）Identification of a cuticle protein with unique repeated motifs in the silkworm, Bombyx mori. Insect Biochem. Molec. Biol. 43, 344-351.
18. 八木勇三，佐藤由紀子，村松由記子，原高明，相垣敏郎 (2013) ショウジョウバエの寿命に対する赤ワイン由来ポリフェノールProtocatechuic acid の効果. Food function (in press).
19. *Sakai, T., Inami, S., Sato, S., Kitamoto, T. (2012) Fan-shaped body neurons are involved in period-dependent regulation of long-term courtship memory in Drosophila. Learning & Memory 19: 571-574.
20. Tomioka S, Aigaki T, Matsuo T. (2012) Conserved cis-regulatory elements of two odorant-binding protein genes, Obp57d and Obp57e, in Drosophila. Genes Genet Syst. 87, 323-329.
21. Kadengodlu PA, Hebishima T, Takeshima SN, Ito M, Liu M, Abe H, Aida Y, Aigaki T, Ito Y. (2012) Positively charged cholesterol-recombinant human gelatins foster the cellular uptake of proteins and murine immune reactions. J Nanomedicine 7, 5437-5450.
22. Amano A, Tsunoda M, Aigaki T, Maruyama N, Ishigami A. (2012) Age-related changes of dopamine, noradrenaline and adrenaline in adrenal glands of mice. Geriatr Gerontol. 13, 490-496.
23. Nakagawa-Yagi Y, Sato Y, Matsumoto E, Nakatsuka SI, Sakaki T, Muramatsu Y, Hara T, Aigaki T. (2012) Pharmacological modulation of histone demethylase activity by a small molecule isolated from subcritical water extracts of Sasa senanensis leaves prolongs the lifespan of Drosophila melanogaster. BMC Complement Altern Med. 12,101.
24. Trindade LS, Balduino A, Aigaki T, Heddle JG. (2012) Senemorphism: a novel perspective on aging patterns and its implication for diet-related biology. Biogerontology. 13,457-466.
25. Takeo S, Swanson SK, Nandanan K, Nakai Y, Aigaki T, Washburn MP, Florens L, Hawley RS. (2012) Shaggy/glycogen synthase kinase 3β and phosphorylation of Sarah/regulator of calcineurin are essential for completion of Drosophila female meiosis. Proc Natl Acad Sci U S A. 109, 6382-6389.
26. Kishita Y, Tsuda M, Aigaki T. (2012) Impaired fatty acid oxidation in a Drosophila model of mitochondrial trifunctional protein (MTP) deficiency. Biochem Biophys Res Commun. 419, 344-349.
27. Harada E, Nakagawa J, Asano T, Taoka M, Sorimachi H, Ito Y, Aigaki T, Matsuo T. (2012) Functional evolution of duplicated odorant-binding protein genes, Obp57d and Obp57e, in Drosophila. PLoS One. 7, e29710.
28. Takeo S, Swanson SK, Nandanan K, Nakai Y, Aigaki T, Washburn MP, Florens L, Hawley RS. (2012) Shaggy/glycogen synthase kinase 3β and phosphorylation of Sarah/regulator of calcineurin are essential for completion of Drosophila female meiosis. Proc Natl Acad Sci U S A, 109, 6382-6389.
29. Kishita Y, Tsuda M, Aigaki T. (2012) Impaired fatty acid oxidation in a Drosophila model of mitochondrial trifunctional protein (MTP) deficiency. Biochem Biophys Res Commun. 419, 344-349.
30. Harada E, Nakagawa J, Asano T, Taoka M, Sorimachi H, Ito Y, Aigaki T, Matsuo T. (2012) Functional evolution of duplicated odorant-binding protein genes, Obp57d and Obp57e, in Drosophila. PLoS One, 7, e29710.
31. Kourosh Shahpasand, Isao Uemura, Taro Saito, Tsunaki Asano, Kenji Hata, Keitaro Shibata, Yoko Toyoshima, Masato Hasegawa and Shin-ichi Hisanaga,（2012）Regulation of mitochondrial transport and inter-microtubule spacing by Tau phosphorylation at the sites hyperphosphorylated in Alzheimer’s disease, J. Neuroscience, 32, 2430-2441.
32. Tomita J, Mitsuyoshi M, Ueno T, Aso Y, Tanimoto H, Nakai Y, Aigaki T, Kume S, Kume K. (2011) Pan-neuronal knockdown of calcineurin reduces sleep in the fruit fly, Drosophila melanogaster. J Neurosci. 31, 13137-13146.
33. Amano A, Handa S, Aigaki T, Shigemoto K, Maruyama N, Ishigami A. (2011) Establishment and characterization of hepatocytes from an Immortomouse/SMP30/GNL knockout mouse hybrid lacking vitamin C to study vitamin C transport. J Biochem. 150, 671-678.
34. Nakai Y, Horiuchi J, Tsuda M, Takeo S, Akahori S, Matsuo T, Kume K, Aigaki T. (2011) Calcineurin and its regulator sra/DSCR1 are essential for sleep in Drosophila. J Neurosci, 3012759-12766.
35. Wang W, Hara S, Liu M, Aigaki T, Shimizu S, Ito Y. (2011) Polypeptide aptamer selection using a stabilized ribosome display. J Biosci Bioeng, 112, 515-517.
36. Rotkopf S, Hamberg Y, Aigaki T, Snapper SB, Shilo BZ, Schejter ED. (2011) The WASp-based actin polymerization machinery is required in somatic support cells for spermatid maturation and release. Development, 188, 105-125.
37. 坂井貴臣（2011）「ショウジョウバエメスの性行動の神経遺伝学的研究」　比較生理生化学 28: 225-230.
38. Brumby AM, Goulding KR, Schlosser T, Loi S, Galea R, Khoo P, Bolden JE, Aigaki T, Humbert PO, Richardson HE. (2011） Identification of Novel Ras-cooperating Oncogenes in Drosophila melanogaster: A RhoGEF/Rho-family/JNK Pathway is a Central Driver of Tumorigenesis. Genetics, 188, 105-125.
39. Funakoshi M, Tsuda M, Muramatsu K, Hatsuda H, Morishita S, Aigaki T. (2011） A gain-of-function screen identifies wdb and lkb1 as lifespan-extending genes in Drosophila. Biochem Biophys Res Commun. 405, 667-72.
40. Sakai T and Aigaki T. (2010) The Drosophila calcineurin regulator, Sarah, is involved in male courtship. NeuroReport 21: 985-988.
41. Sakai T and Aigaki T. (2010) Overexpression of a repressor isoform of CrebB-17A lengthens courtship break in the fruit fly Drosophila melanogaster (Diptera: Drosophilidae). Applied Entomology and Zoology 45: 533-539.
42. Tsuda M, Kawaida R, Kobayashi K, Shinagawa A, Sawada T, Yamada R, Yamamoto K, Aigaki T. (2010） POSH promotes cell survival in Drosophila and in human RASF cells. FEBS Lett, 584, 4689-4694.
43. Ueyama M, Akimoto Y, Ichimiya T, Ueda R, Kawakami H, Aigaki T, Nishihara S. (2010） Increased apoptosis of myoblasts in Drosophila model for the Walker-Warburg syndrome. PLoS One, 5, e11557.
44. Yasukawa J, Tomioka S, Aigaki T, Matsuo T. (2010） Evolution of expression patterns of two odorant-binding protein genes, Obp57d and Obp57e, in Drosophila. Gene, 467, 25-34.
45. Yamazaki D, Horiuchi J, Miyashita T, Saitoe M. (2010） Acute inhibition of PKA activity at old ages ameliorates age-related memory impairment in Drosophila. J Neurosci, 30, 15573-15577.
46. Tsuda M, Ootaka R, Ohkura C, Kishita Y, Seong KH, Matsuo T, Aigaki T. (2010） Loss of Trx-2 enhances oxidative stress-dependent phenotypes in Drosophila. FEBS Lett, 584, 3398-401.
47. Takeo S, Hawley RS, Aigaki T. (2010） Calcineurin and its regulation by Sra/RCAN is required for completion of meiosis in Drosophila. Dev Biol, 344, 957-67.
48. Tsuda M, Kobayashi T, Matsuo T, Aigaki T. (2010） Insulin-degrading enzyme antagonizes insulin-dependent tissue growth and Abeta-induced neurotoxicity in Drosophila. FEBS Lett, 584, 2916-20.
49. Amano A, Aigaki T, Maruyama N, Ishigami A. (2010) Ascorbic acid depletion enhances expression of the sodium-dependent vitamin C transporters, SVCT1 and SVCT2, and uptake of ascorbic acid in livers of SMP30/GNL knockout mice. Arch Biochem Biophys. 496, 38–44.
50. Ahsan, B., Saito, TL., Hashimoto, S., Muramatsu, K., Tsuda, M., Sasaki, A., Matsushima, K., Aigaki, T. and Morishita, S. (2009) MachiBase: a Drosophila melanogaster 5'-end mRNA transcription database. Nucleic Acids Res. 37, D49-53.
51. Tsubouchi, A., Tsuyama, T., Fujioka, M., Kohda, H., Okamoto-Furuta, K., Aigaki, T. and Uemura, T. (2009) Mitochondrial Protein Preli-like Is Required for Development of Dendritic Arbors and Prevents Their Regression in the Drosophila Sensory Nervous System. Development, 136, 3757-3766.
52. Sakai T, Kasuya J, Kitamoto T and Aigaki T. (2009) The Drosophila TRPA channel, Painless, regulates sexual receptivity in virgin females. Genes, Brain and Behavior 8: 546-557.
53. Ishimoto H,Sakai T, and Kitamoto T. (2009) Ecdysone signaling regulates courtship long-term memory formation in adult Drosophila melanogaster. Proc. Natl. Acad. Sci. USA 106: 6381-6386.
54. Matsuo, T. (2008) Rapid evolution of two odorant-binding protein genes, Obp57d and Obp57e, in the Drosophila melanogaster species group. Genetics 178:1061-1072.
55. Harada, E., Haba, D., Aigaki, T., Matsuo, T. (2008) Behavioral analyses of mutants for two odorant-binding protein genes, Obp57d and Obp57e, in Drosophila melanogaster. Genes Genet. Syst. 83:257-264.
56. Matsuo, T. (2008) Genes for host-plant selection in Drosophila. J. Neurogenetics 22:195-210
57. 松尾隆嗣 (2008) ショウジョウバエの食性の進化　細胞工学 27:1112-1117
58. Matsuno M, Horiuchi J, Tully T, Saitoe M. (2008) The Drosophila cell adhesion molecule klingon is required for long-term memory formation and is regulated by Notch. Proc Natl Acad Sci USA. 106, 310-315.
59. Horiuchi, J., Yamazaki, D., Naganos, S., Aigaki, T. and Saitoe, M. (2008) Protein kinase A inhibits a consolidated form of memory in Drosophila. Proc Natl Acad Sci USA. 105, 20976-20981.
60. List, O., Togawa, T., Tsuda, M., Matsuo, T., Elard, L. and Aigaki, T. (2009) Overexpression of grappa encoding a histone methyltransferase enhances stress resistance in Drosophila. Hereditas, 146, 19-28.
61. Suzuki, E., Zhao Y., Ito, S., Sawatsubashi, S., Murata, T., Furutani, T., Shirode, Y., Yamagata, K., Tanabe, M., Kimura, S., Ueda, T., Fujiyama, S., Lim, J., Matsukawa, H., Kouzmenko, AP., Aigaki, T., Tabata, T., Takeyama, KI, and Kato, S. (2009) Aberrant E2F activation by polyglutamine expansion of androgen receptor in SBMA neurotoxicity. Proc Natl Acad Sci USA.106, 3818-3822.
62. Ahsan, B., Saito, TL., Hashimoto, S., Muramatsu, K., Tsuda, M., Sasaki, A., Matsushima, K., Aigaki, T. and Morishita, S. (2009) MachiBase: a Drosophila melanogaster 5'-end mRNA transcription database. Nucleic Acids Res. 37, D49-53.
63. Shindo, M., Wada, H., Kaido, M., Tateno, M., Aigaki, T., Tsuda, L. and Hayashi, S. (2008) Dual function of Src in the maintenance of adherens junctions during tracheal epithelial morphogenesis. Development 135, 1355-1364
64. 木下善仁，津田学，相垣敏郎 (2008) TCA回路を中心とした代謝調節と寿命制御，基礎老化研究 32, 21-23.
65. Kaji, K., Tomino, S., and Asano, T. (2009) A serine protease in the midgut of the silkworm, Bombyx mori: Protein sequencing, identification of cDNA, demonstration of its synthesis as zymogen form and activation during midgut remodeling. Insect Biochem and Mol biol. 39. 207-17.
66. Asano, T. and Takebuchi, K. (2009) Identification of the gene encoding pro-phenoloxidase A3 in the fruitfly, Drosophila melanogaster. Insect Mol Biol. 18, 223-232
67. Nam, H-J. Jang, I-H., Asano, T. and Lee, W-J. (2008) Involvement of pro-phenoloxidase 3 in lamellocyte-meidated spontaneous melanization in Drosophila. Molecular and Cells. 2008. 2, .606-610
68. Yao, Y., Wu, Y., Yin, C., Ozawa, R., Aigaki, T., Wouda, R.R., Noordermeer, J.N., Fradkin, L.G., Hing, H. (2007) Antagonistic roles of Wnt5 and the Drl receptor in patterning the Drosophila antennal lobe. Nat Neurosci. 10, 1423-1432
69. Taniguchi K, Hozumi S, Maeda R, Ooike M, Sasamura T, Aigaki T, Matsuno K. (2007) D-JNK signaling in visceral muscle cells controls the laterality of the Drosophila gut. Dev Biol. 311, 251-263
70. Tsuda M, Sugiura T, Ishii T, Ishii N, Aigaki T. (2007) A mev-1-like dominant-negative SdhC increases oxidative stress and reduces lifespan in Drosophila. Biochem Biophys Res Commun. 363, 342-346.
71. Sakurai T, K., Kojima, T., Aigaki, T., *Hayashi, S (2007) Differential control of cell affinity required for progression and refinement of cell boundary during Drosophila leg segmentation, Dev Biol, 309, 126-136
72. Matsuo, T., Sugaya, S., Yasukawa, J., Aigaki, T., Fuyama, Y. (2007) Odorant-Binding Proteins OBP57d and OBP57e Affect Taste Perception and Host-Plant Preference in Drosophila sechellia. PLoS Biology. 5(5):e118
73. Umeda-Kameyama, Y., Tsuda, M., Ohkura, C., Matsuo, T., Namba, Y., Ohuchi, Y. and Aigaki, T. (2007) Thioredoxin suppresses Pael-R-induced neurotoxicity and extends longevity in Drosophila. J. Biol. Chem. 282, 11180-11187.
74. Shima, S., Aigaki, T., Nojima, T. and Yamamoto, D. (2007) Identification of trf2 mutants of Drosophila with defects in anterior spiracle eversion. Arch. Insect Biochem. Physiol. 64, 157-163.