Project/Area Number |
10145107
|
Research Category |
Grant-in-Aid for Scientific Research on Priority Areas (A)
|
Allocation Type | Single-year Grants |
Research Institution | Kyoto University |
Principal Investigator |
TANAKA Atsuo Graduate School of Engineering, Kyoto University, Professor, 大学院・工学研究科, 教授 (80026088)
|
Co-Investigator(Kenkyū-buntansha) |
AKIYOSHI Kazunari Graduate School of Engineering, Kyoto University, Associate Professor, 大学院・工学研究科, 助教授 (90201285)
NAGAMUNE Teruyuki Graduate School of Engineering, The University of Tokyo, Professor, 大学院・工学系研究科, 教授 (20124373)
|
Project Period (FY) |
1998 – 2001
|
Project Status |
Completed (Fiscal Year 2001)
|
Budget Amount *help |
¥89,200,000 (Direct Cost: ¥89,200,000)
Fiscal Year 2000: ¥30,100,000 (Direct Cost: ¥30,100,000)
Fiscal Year 1999: ¥28,700,000 (Direct Cost: ¥28,700,000)
Fiscal Year 1998: ¥30,400,000 (Direct Cost: ¥30,400,000)
|
Keywords | Cell surface / Arming yeast / Biomass / Anti-hen egg lysozyme / growth factor / Chimeric receptor / cell-surface saccharides / lipospme / 細胞表層工学 / 酵母 / アーミング / アンカリング / ペプチド / 抗体-受容体キメラ / シグナル伝達 / 分子ターゲティング / リパーゼ / キメラ受容体 / 抗体 / エリスロポエチン / シアル酸 / 新機能細胞 / 抗体可変領域 / c-Kit / ガングリオシド |
Research Abstract |
In cell surface, many recepter proteins are presented and the specific biomolecules are recognized by these recepter proteins. These mechanisms can be analyzed from chemical view points. To systemize the biotergeting, the cell sueface design was investigated. Dr. Tanaka studied the development of novel yeast cells armed with enzymes and functional proteins (glucoamylase, α-amylase, CM-cellulase, β-glucosidase, lipase, a histidine oligomer. green fluorescent protein, and its variants). The yeasts were constructed by a cell surface engiseering system of yeast Sacebaromyces cerevisiae, which can assimilate the redundant biomass or can display the vaccine protein. These surface-engineered yeast cells are termed as "Arming yeasts". "Cell surface engineering" will be capable of conferring novel additional abilities upon living cells and will herald a new era in the field of biotechnology. Dr. Nagamune Studied a way of changing the binding element of a growth factor so as to alter its specificity of specific ligand-receptor pairs. By joining these antibody variable domains, VH and VL, of anti-hen egg lysozyme (HEL) antibody HyHEL-10 to the cytoplasmic portion of erythropoietin receptor (EpoR), a chimeric receptor that could he activated by HEL was developed. When IL-3-dependent murine myeloid 32D cells were co-transfected with plasmids encoding VH-EpoR and VL-EpoR-IRES-EGFP, HEL induced selective expansion of the cell population with high expression level of EGFP. To expand the current approach, chimeric receptors whose cytoplasmic domain was replaced by that of gp 130 were developed. Dr. Akiyoshi studied the functions of cell-surface saccharides using liposomal displaying systems as model biological membrane. It was demonstrated that 1) function of gangliosides-conatining liposomes, 2) coating of phytylphosphate giant vesicles with a hydrophobized polysaccharide 3) dynamic morphological changes of cell-size liposomes in the presence of gangliosides.
|