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研討會公告              ● 生化所行事曆

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2018 / 8 月份 演講
演講題目 From Seeing to Believing: Visualization and Tracking of Extracellular Vesicles
時間 年/月/日 2018/8/16 11:00 ~ 12:00
地點 生化所114室
主講人 賴品光博士
主講人背景 中央研究院原子與分子科學研究所助研究員
演講主持人 徐尚德副研究員
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 Extracellular vesicles (EVs), including exosomes and microvesicles, are nanosized, membrane-bound vesicles released in abundance by cancer cells. These EVs are capable of delivering a select subset of proteins and RNAs designed to promote tumor growth and metastases. However, the exact time, location (i.e. spatiotemporal properties) and cargo delivery capacity of EVs remained unknown due to a lack of available methods to detect them. Here we engineered bioluminescent and fluorescent reporter systems which allow EV visualization in real-time both in vitro and in vivo. The multimodal bioluminescent reporter labels EVs with a membrane-bound variant of Gaussia luciferase fused to a biotin acceptor peptide, thereby enabling whole-animal multimodal imaging, as well as pharmacokinetics analysis of EVs. We further developed a bifunctional fluorescent EV/EV-RNA reporters to study multiple EV populations with subcellular imaging resolution. By multiplexing the fluorescent and bioluminescent EV reporters, we elucidated the rapid dynamics of tumor EV uptake and translation of EV-delivered cargo mRNAs in cancer cells. These novel molecular imaging platforms revealed that EV mediates a dynamic and multidirectional communication between cells with delivery of functional mRNA, thereby manipulating its recipient cells at neighboring and distal sites.-Dr. Charles Pin-Kuang Lai
 
演講題目 Structure and functional analysis of secondary metabolite enzymes
時間 年/月/日 2018/8/29 15:00 ~ 16:00
地點 生化所114室
主講人 Dr. Takahiro Mori
主講人背景 日本東京大學藥學科學研究所助教授
演講主持人 林曉青助研究員
洽詢人員 劉小姐
洽詢電話 02-27855696#1165
洽詢信箱 liukchun@gate.sinica.edu.tw
演講摘要 The structural analysis of secondary metabolite enzymes provides us important information for structure-based engineering of these enzymes to generate. unnatural novel compounds. Here, I will talk about structure analyses of two distinct enzymes, which are involved in the biosynthesis of indole alkaloid and terpenoid compound, respectively. Cytochrome P450 enzymes catalyze variety of chemical reactions such as hydroxylation, desatulation, and cyclization. The P450 enzymes TleB and HinD catalyze unusual C-N bond formation in the biosynthesis of teleocidin B. These enzymes accept N-methyl-L-valyl-L-tryptophanol as a substrate to generate indolactam V. This C-N bond forming reaction between secondary amine and non-activated C4 position of indole ring are chemically challenging reaction. The biochemical characterization of these enzymes revealed that HinD showed the broader substrate specificity for unnatural substrates compared to that of TleB. Furthermore, the mechanistic analysis of these enzymes by using precursor-directed and structure-based approaches suggested that C-N bond formation is proceeded via epoxidation reaction of C2-C3 of indole ring. Terpene synthase (TPS) and prenyltransferase (PT) are two key enzymes for the diversification and complication of terpenoids structures, and these enzyme families are normally separate and independent enzymes. Interestingly, the enzyme AaT08897 from Alternaria alternata TPF6 is an unusual TPS enzyme, which catalyzes both of cyclization reaction of farnesyl diphosphate and prenylation of dimethylallyl diphosphate to N1 and C3 of indole to generate 7-epi-α-selinene and mono- or di-prenylated indole products, respectively. We have successfully obtained X-ray crystal structures of apo-structure and FPP binding structure of AaT08897. The overall structure of AaT08897 shared typical domain structure of class I TPS structure. However, it possessed a larger hydrophobic cavity in the active site and a ~80 residues additional region at N terminal compared to the other microbial TPSs. The mutagenesis study based on the crystal structures are ongoing to understand the molecular bases of bifanctional AaT08897 enzyme reaction.-Dr. Takahiro Mori
 

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