Bottom-up approach to elucidate the molecular basis of immunomodulation by sialylglycans
| Project/Area Number |
20K05727
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 37020:Chemistry and chemical methodology of biomolecules-related
|
|---|
| Research Institution | Osaka University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2020-04-01 – 2023-03-31
|
| Project Status |
Completed (Fiscal Year 2022)
|
| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
|
|---|
| Keywords | 糖鎖 / シアル酸 / 免疫 / 糖鎖合成 / 糖鎖編集 / 複合化 / シグレック / 合成生物学 |
|---|
| Outline of Research at the Start |
細胞表面では無数の構造のシアリル糖鎖が不均一に存在し，cis（同一細胞上）およびtrans（細胞外）でSiglecと相互作用し，免疫を制御する．本研究では，合成糖鎖をプローブとして用いたボトムアップアプローチにより，シアル酸の形成する生体分子社会の解明を目指す．まず，i) シアリル糖鎖をライブラリ合成し，ii) Siglecによるシアリル糖鎖認識を分子レベルで解析する．さらに，合成糖鎖の細胞表面への提示システムを用い，iii) 生細胞系でSiglecとのcis，transの相互作用を厳密に評価する．加えて，vi) 糖鎖の不均一性（グリコフォーム）を再構成した系での解析も実施する．
|
| Outline of Final Research Achievements |
In this study, we elucidated the immune regulation mechanism by sialic acid-containing glycans through a bottom-up approach using synthetic glycans as probes. First, we synthesized a library of sialylglycans. The synthesized glycans were then employed for the analysis of their recognition mechanism by sialic acid recognition lectins, including Siglec, at the molecular level. Furthermore, we developed a system to present synthetic glycans on the cell surface, and analyzed the interaction between glycans and lectins using living cell system. Through this research, we have constructed the fundamental methodology for the synthesis of sialylglycans. In addition, we clarified the molecular basis of sialic acid recognition. We also pioneered an innovative method to elucidate the functions of cell surface glycans and developed a novel glycan-based immunoregulatory method.
|
| Academic Significance and Societal Importance of the Research Achievements |
本研究の特徴は，合成糖鎖を用いて，分子レベルでの糖鎖認識の解析，細胞膜上での機能解析を実施した点である．糖鎖機能の解析は，糖鎖生合成酵素のノックアウトなどの分子生物学的手法を中心に進められてきた．これらの研究と合成糖鎖を用いた化学的なアプローチをとる本研究は相補的で，分子レベルでの糖鎖機能解析が進み，糖質科学の発展に大きく貢献した．また，Siglecは免疫応答に関わることから，自己免疫疾患やアレルギーといった疾病，免疫療法の開発などと関連が深い．そのため，シアリル糖鎖とSiglecの相互作用解明は，創薬への展開も期待でき，波及効果も大きい．
|
Report
(4 results)
Research Products
(85 results)
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
[Journal Article] α‐Emitting cancer therapy using 211 At‐AAMT targeting LAT12021
Author(s)
Kaneda‐Nakashima Kazuko、Zhang ZiJian、Manabe Yoshiyuki、Shimoyama Atsushi、Kabayama Kazuya、Watabe Tadashi、Kanai Yoshikatsu、Ooe Kazuhiro、Toyoshima Atsushi、Shirakami Yoshifumi、Yoshimura Takashi、Fukuda Mitsuhiro、Hatazawa Jun、Nakano Takashi、Fukase Koichi、Shinohara Atsushi
-
Journal Title
Cancer Science
Volume: 112
Issue: 3
Pages: 1132-1140
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
[Journal Article] Unveiling Molecular Recognition of Sialoglycans by Human Siglec-102020
Author(s)
Forgione Rosa Ester、Di Carluccio Cristina、Guzman-Caldentey Juan、Gaglione Rosa、Battista Filomena、Chiodo Fabrizio、Manabe Yoshiyuki、Arciello Angela、Del Vecchio Pompea、Fukase Koichi、Molinaro Antonio、Martin-Santamaria Sonsoles、Crocker Paul R.、Marchetti Roberta、Silipo Alba
-
Journal Title
iScience
Volume: 23
Issue: 6
Pages: 101231-101231
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
[Presentation] Study of N-glycan from thermophilic archaeon, Thermocossus kodakarensis: isolation, structural, determination, and synthesis2022
Author(s)
Kohtaro Hirao, Yoshiyuki Manabe, Immacolata Speciale, Anna Notaro, Haruyuki Atomi, Antonio Molinaro, Cristina De Castro, Koichi Fukase
Organizer
30th International Carbohydrate Symposium
Related Report
Int'l Joint Research
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
[Presentation] Immunological Evaluation of Conjugate/Co-Assembly of Peptide Antigen and Adjuvant as Self-adjuvanting Anti-breast Cancer Candidates2020
Author(s)
Keita Ito, Yoshiyuki Manabe, Taku Aiga, Tsung-Che Chang, Kazuya Kabayama, Shino Ohshima, Yoshie Kametani, Hiroto Furukawa, Hiroshi Inaba, Kazunori Matsuura, and Koichi Fukase
Organizer
第57回ペプチド討論会
Related Report
-
-
-
-
