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研討會公告              ● 生化所行事曆

月   
2018 / 10 月份 演講
演講題目 Stimulation of Hsp90 chaperone function by the derivative of anti-cancer compound: A potential molecular intervention for neuropathy
時間 年/月/日 2018/10/3 10:30 ~ 11:10
地點 生化所114室
主講人 Dr. Tapan K. Chaudhuri
主講人背景 印度理工學院生物科學院教授
演講主持人 林俊宏研究員
洽詢人員 劉小姐
洽詢電話 02-27855696#1165
洽詢信箱 liukchun@gate.sinica.edu.tw
演講摘要 Heat Shock Protein 90 (Hsp90) is a eukaryotic chaperone responsible for the folding and functional activation of numerous client proteins in the cell. Some of these clients are found to be mutated in cancer tissues, and assume either a non-functional or a highly functional state that aids in disease propagation. These mutated client proteins also require Hsp90s chaperoning function to attain their functional form. Thus, inhibiting chaperone functions of Hsp90 could partially or completely prevent the progression of cancer as these client ‘onco-proteins’ would not be able to achieve their functional state. Inhibiting Hsp90 chaperone functions by potential inhibitors has therefore been pursued with great interest, and libraries of potential inhibitors have come into existence. A few of these compounds have reached the Phase Trials, and are being studied in combination with other modes of therapy to treat certain types of cancer. A major fraction of these compounds are amino terminal inhibitors, which competitively disrupt ATP binding and prevent the maturation of client proteins by preventing Hsp90 from completing its ATPase cycle. The other relatively less-studied class of inhibitors of Hsp90 are the ones that bind to the carboxy terminus of the chaperone. Some of these compounds disrupt Hsp90-cochaperone and/or chaperone-client interactions, although how these compounds affect the structure-function relationship of Hsp90 is not well elucidated. Here we have determined the exact location of binding of KU-32, a synthetic analogue of the well characterized Hsp90 carboxy terminus inhibitor Novobiocin (NB). We have investigated its effect on the overall conformation of the chaperone and the impact of these structural changes on the functioning of the Hsp90 chaperone. Thereafter, combinatorial studies with Geldanamycin, an amino terminal Hsp90 inhibitor, and NB/KU-32, were conducted to investigate possible synergy or antagonism, with respect to the function of Hsp90. Our results demonstrate that the binding of NB and KU-32 induced completely opposite conformational changes in Hsp90 despite having minor structural differences between them. Another very significant finding from our biochemical studies suggest that in contrast to the well characterized inhibitor NB which acts by abrogating Hsp90-client and Hsp90-co-chaperone interactions, and hence reduces client maturation. KU-32 binding to the carboxy terminus of Hsp90 stimulates its function by allosteric modulation of the amino-terminal domain which is involved in ATP binding and hydrolysis. Further, in-silico analysis revealed global structural changes associated with KU-32 binding that stretched from one terminus of the chaperone to the other, allowing Hsp90 to adopt a unique conformation that preferentially binds ATP. KU-32 is also observed to facilitate enhanced refolding of thermally denatured client substrates of Hsp90. KU-32 displays all the properties that might prove useful in designing second-generation compounds, which could potentially aid in the treatment of degenerative disorders. Enhanced ATP hydrolysis by Hsp90, leading to faster client folding, could prevent large-scale accumulation of misfolded or partially folded proteins, thereby reducing or completely mitigating the abnormalities associated with neuropathies.-Dr. Tapan K. Chaudhuri
 
演講題目 L-Asparginase of intracellular pathogens: Metabolic target and its role in antibiotic resistance
時間 年/月/日 2018/10/3 11:20 ~ 12:00
地點 生化所114室
主講人 Dr. Bishwajit Kundu
主講人背景 印度理工學院生物科學院副教授
演講主持人 林俊宏研究員
洽詢人員 劉小姐
洽詢電話 02-27855696#1165
洽詢信箱 liukchun@gate.sinica.edu.tw
 
演講題目 The origin of sleep defects in Parkinson's Disease
時間 年/月/日 2018/10/17 9:00 ~ 9:50
地點 生化所103講堂
主講人 Dr. Patrik Verstreken
主講人背景 比利時腦與疾病研究VIB-KU Leuven Center科學主任
演講主持人 姚季光助研究員
洽詢人員 劉小姐
洽詢電話 02-27855696#1165
洽詢信箱 liukchun@gate.sinica.edu.tw
 
演講題目 Reading and writing histone marks in genome expression/maintenance and cancer
時間 年/月/日 2018/10/17 9:50 ~ 10:40
地點 生化所103講堂
主講人 Dr. Jacques Côté
主講人背景 加拿大拉瓦爾大學分子生物、醫學生物化學、病理學教授
演講主持人 黃馥助研究員
洽詢人員 劉小姐
洽詢電話 02-27855696#1165
洽詢信箱 liukchun@gate.sinica.edu.tw
 
演講題目 Genetically encoded natural non-canonical amino acids
時間 年/月/日 2018/10/22 11:00 ~ 12:00
地點 生化所103講堂
主講人 Dr. Dieter Söll
主講人背景 美國國家院士與美國耶魯大學分子生物物理及生物化學研究所與化學研究所教授
演講主持人 王彥士助研究員
洽詢人員 劉小姐
洽詢電話 02-27855696#1165
洽詢信箱 liukchun@gate.sinica.edu.tw
 
演講題目 TGF-β signaling in the control of epithelial-mesenchymal transdifferentiation
時間 年/月/日 2018/10/29 11:00 ~ 12:00
地點 生化所114室
主講人 Dr. Rik Derynck
主講人背景 美國加州大學舊金山分校細胞組織生物學與解剖研究所教授
演講主持人 陳瑞華特聘研究員
洽詢人員 劉小姐
洽詢電話 02-27855696#1165
洽詢信箱 liukchun@gate.sinica.edu.tw
演講摘要 In mammals, thirty-three genes encode structurally related polypeptides that combine into homodimeric or heterodimeric, secreted TGF-β family proteins. These control a variety of physiological processes and act prominently as differentiation factors in most lineages during normal development, while their deregulated expression and signaling contribute to various pathologies. TGF-β1 is seen as the prototype of the TGF-β family of differentiation factors, and much about what we learn about TGF-β signaling can be conceptually extended to other TGF-β family proteins. Increased TGF-β signaling represses the epithelial phenotype and induces mesenchymal characteristics, including increased cell motility and invasion, which is of high relevance during progression of carcinomas and in fibrosis. The loss of epithelial characteristics and transition toward a mesenchymal phenotype has been named epithelial-mesenchymal transition (EMT). During development, EMT is controlled by TGF-β-related proteins, including bone morphogenetic proteins, whereas EMT associated with wound healing, cancer progression and fibrosis are most commonly driven by increased TGF-β signaling. In my talk, I will concisely review the molecular basis of TGF-β family signaling initiated by ligand binding to complexes of dual-specificity transmembrane kinases that subsequently activate Smad signaling as well as non-Smad signaling pathways, including Erk MAPK signaling and PI3k-Akt-mTOR signaling. I will also discuss the EMT process itself, and its relevance in development, its role in carcinomas and its physiological link to epithelial and cancer stem cells. I will further discuss how TGF-β signaling cooperates with other pathways in initiating and directing EMT and the generation of the epithelial/carcinoma stem cell phenotype. Finally, I will discuss the cooperation of TGF-β-induced Smad and non-Smad signaling in the progression of EMT and the transition from a reversible EMT toward stabilization of the EMT phenotype.-Dr. Rik Derynck
 

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