| Project/Area Number |
17K15076
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Structural biochemistry
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| Research Institution | Yokohama City University |
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Principal Investigator |
Ohki Mio 横浜市立大学, 生命医科学研究科, 特任助教 (10791361)
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | 光遺伝学 / 構造生物学 / 光活性化アデニル酸シクラーぜ / 構造解析 / セカンドメッセンジャー |
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| Outline of Final Research Achievements |
Optogenetics is a rapidly growing field in which light is used to control biological systems. We show that Oscillatoria acuminata photoactivated adenylate cyclase (OaPAC) protein produces the fundamental second messenger cyclic-AMP (cAMP) in response to blue light, is stable and functional in different mammalian cell types, and can be used to trigger events by raising cAMP level. OaPAC consists of a catalytic domain controlled by a photosensitive blue light using flavin (BLUF) domain. We have solved the crystal structure.Based on structural elucidation of the OaPAC activate mechanism, application development of light control second messenger in cells, development of cGMP production enzyme by adenylate cyclase domain modification and aiming for basic medical research to medical treatment such as neural circuit formation disease by optogenetics.
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| Academic Significance and Societal Importance of the Research Achievements |
光活性化アデニル酸シクラーゼ（PAC）は特性解明や生物機能光制御への展開も提唱・実行されており、また藍藻由来のPACである、OaPACの立体構造解明に成功し、光活性化機構に関する構造生物学的な研究は本研究グループが先駆的に積み上げてきた。
近年、「光遺伝学」が急速に普及し、OaPACによるcAMPを介する生体機能光制御は、光発生医学現象の制御・解明・治療・創薬スクリーニングという広大な新分野の開拓を先導かつ独創的な新領域の研究分野であると言える。本研究により今後、構造生命科学的解析を基盤として、優れた特性の改良型OaPACの創出とそれに基づく広範で多彩な応用展開につながることが期待できる。
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