Optical control of MAPK signaling for understanding of cell-fate decision mechanisms
| Project/Area Number |
16K07304
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Functional biochemistry
|
|---|
| Research Institution | Toho University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2016-04-01 – 2019-03-31
|
| Project Status |
Completed (Fiscal Year 2018)
|
| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
|---|
| Keywords | 炎症 / キナーゼ / イメージング / 光遺伝学 / 光制御 / MAPK / ストレス応答 / 細胞死 / 光操作 / シグナル伝達 / MAPキナーゼ |
|---|
| Outline of Final Research Achievements |
The spatial and temporal variation of intracellular signaling may play role in determining cell fates by inducing different cellular functions.In this study, the dynamics of intracellular kinases in living cells was investigated by developing the novel tools to quantitatively evaluate and control kinase activity for understanding its physiological significance. It was found that inflammatory IL-1beta stimuli elicits JNK activity only transiently because of the negative feedback inhibitory mechanism lying downstream of p38. In addition, optical control of p38 activity in living cells was achieved by developing a new tool which is composed of light-responsive domains and a kinase domain.
|
| Academic Significance and Societal Importance of the Research Achievements |
光を用いて生きた細胞内の情報伝達機構を解析する手法の開発が世界的に盛んに行われており、身体の部位特異的に遺伝子操作や細胞機能を制御することが可能になりつつある。光による神経活動操作法が開発されて以来、光操作は神経科学研究などに多用されているものの、細胞内シグナルを直接的に光で制御するものは少なく、がんや免疫異常などの治療法探索に資する光操作技術は十分ではない状況である。本研究では世界に先駆けてMAPK活性操作手法の開発に取り組み、炎症応答や細胞ストレスの中心経路であるp38経路の活性制御手法の実現に成功した。また、JNK活性の可視化によりp38とJNKに新しい連関機構を見出すことにも成功した。
|
Report
(4 results)
Research Products
(13 results)
-
[Journal Article] A FRET biosensor for necroptosis uncovers two different modes of the release of DAMPs.2018
Author(s)
Murai S, Yamaguchi Y, Shirasaki Y, Yamagishi M, Shindo R, Hildebrand JM, Miura R, Nakabayashi O, Totsuka M, Tomida T, Adachi-Akahane S, Uemura S, Silke J, Yagita H, Miura M, Nakano H
-
Journal Title
Nat Commun
Volume: 9
Issue: 1
Pages: 4457-4457
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
-
-
-
-
-
-
-
-
-
