生命科學暨醫學院教師傑出研究介紹
Introduction to Outstanding Research by Faculty Members of the College of Life Sciences and Medicine
分子醫學研究所 林玉俊教授
Professor Yu-Chun Lin, Institute of Molecular Medicine
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清華分醫所特聘教授林玉俊(中)帶領研究助理陳筱奇(右)、碩士生曾能杰(左),開發細胞運輸定身術「鉚釘系統」。 Professor Yu-Chun Lin, Distinguished Professor at the Institute of Molecular Medicine, National Tsing Hua University (center), together with research assistant Hsiao-Chi Chen (right) and master’s student Neng-Chieh Tseng (left), has developed a cell transport immobilization technique called the “Rivet System.” 清華分醫所特聘教授林玉俊(左)指導碩士生曾能杰(右)以光照控制線蟲定住不動。 Professor Yu-Chun Lin, Distinguished Professor at the Institute of Molecular Medicine, National Tsing Hua University (left), guided master’s student Neng-Chieh Tseng (right) in controlling C. elegans immobilization through light exposure. 林玉俊研究團隊使用特定波長的藍光控制細胞內的運輸系統。 Professor Yu-Chun Lin’s research team utilizes blue light of specific wavelengths to control intracellular transport systems. 論文第一作者陳筱奇以高階顯微鏡觀察細胞內的運輸系統。 The first author of the paper, Shiau-Chi Chen, observed intracellular transport systems using advanced microscopy.
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Precise Control of Intracellular Trafficking and Receptor-Mediated Endocytosis in Living Cells and Behaving Animals |
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先進科學Advanced Science |
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主持人Principle Investigator: 林玉俊 教授Yu-Chun Lin, Professor 國立清華大學生命科學暨醫學院 分子醫學研究所 Institute of Molecular Medicine (IMM), College of Life Science and Medicine (CLSM), National Tsing Hua University (NTHU). 參與者Participants:: 陳筱奇 國立清華大學生命科學暨醫學院 分子醫學研究所 Shiau-Chi Chen, Institute of Molecular Medicine (IMM), College of Life Science and Medicine (CLSM), National Tsing Hua University (NTHU). 曾能杰 國立清華大學生命科學暨醫學院 分子醫學研究所 Neng-Jie Zeng, Institute of Molecular Medicine (IMM), College of Life Science and Medicine (CLSM), National Tsing Hua University (NTHU). 劉雅良 國立清華大學生命科學暨醫學院 分子醫學研究所 Grace Y. Liu, Institute of Molecular Medicine (IMM), College of Life Science and Medicine (CLSM), National Tsing Hua University (NTHU). |
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摘要 Abstract |
細胞內的運輸系統就如同一座城市的物流網絡,快速且複雜,對於研究其動態機制是一大挑戰。清華大學林玉俊教授團隊研發出全新技術「RIVET」,能在幾秒內透過光照精準、可逆地暫停特定運輸泡泡,實現前所未有的操控精度。該系統已成功應用於培養細胞與實驗動物中,控制突觸訊號傳遞與病毒入侵等關鍵生理過程。RIVET的突破性在於不需長時間基因操控或藥物處理,即可即時分析胞內運輸與疾病機制。研究目標在於開發一套時空精準、可廣泛應用的胞內運輸控制平台,以深入解析胞內物流系統對細胞功能、神經傳導、老化與病原感染的影響,並為相關疾病治療開啟新契機。 Intracellular trafficking is a dynamic and complex transport network critical for cellular function, yet its rapid speed poses a major challenge to scientific investigation. To overcome this, Professor Yu-Chun Lin’s team at National Tsing Hua University has developed RIVET (Rapid Immobilization of target Vesicles on Engaged Tracks), a novel optogenetic tool that enables reversible, vesicle-specific immobilization within seconds. RIVET has been successfully applied in both cultured cells and live animals, allowing precise control of synaptic transmission and receptor-mediated endocytosis. Unlike traditional methods requiring lengthy gene manipulation or chemical inhibitors, RIVET offers real-time, spatiotemporal control without off-target effects. The aim of this research is to establish a robust and versatile platform for dissecting intracellular trafficking across diverse physiological and pathological contexts, including neurocommunication, aging, viral infection, and metabolic regulation—ultimately paving the way for therapeutic interventions targeting disrupted transport mechanisms. |
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研究成果Result/Contributions |
本研究成功開發出一套創新性的胞內運輸操控技術——RIVET(Rapid Immobilization of target Vesicles on Engaged Tracks),可在數秒內利用光照將細胞內特定運輸泡泡即時「定住」,並在關閉光源後恢復其移動。該系統具備高度時空解析度與可逆性,可應用於各類胞內運輸途徑,包括溶酶體、胞吞泡泡、突觸泡泡、以及ACE2介導的病毒進入路徑等。 本團隊進一步將RIVET技術成功應用於活體實驗動物中,證明其可用於操控神經傳遞並即時改變行為,例如可透過藍光暫停線蟲的蠕動行為。該成果不僅讓胞內囊泡運輸的即時觀察與功能驗證成為可能,也為探討神經功能、老化機制與病原體感染開啟了新方向。 此外,RIVET已被證明可有效阻斷新冠病毒的早期入侵階段,顯示其於感染控制與藥物開發具潛力。與傳統基因敲除或藥物處理方法相比,RIVET能在不干擾細胞整體環境的情況下快速、精準地調控胞內運輸,為細胞生物學研究提供前所未有的技術支援。相關成果已發表於國際頂尖期刊《Advanced Science》,顯示此技術具國際影響力與應用潛力。 This project led to the development of RIVET (Rapid Immobilization of target Vesicles on Engaged Tracks), an innovative tool that enables real-time and reversible control of intracellular trafficking using light. With high spatiotemporal precision, RIVET can instantly immobilize specific vesicles—such as endosomes, lysosomes, synaptic vesicles, and ACE2-positive vesicles—within seconds upon light stimulation and allow their normal transport to resume when the light is turned off. We successfully demonstrated RIVET’s applicability in living organisms, including C. elegans, where light-induced immobilization of synaptic vesicles resulted in temporary paralysis of locomotion. This provides a powerful platform to study the dynamic roles of intracellular trafficking in neural communication, aging, metabolism, and pathogen entry. One notable application of RIVET was the inhibition of SARS-CoV-2 entry by blocking the early phase of ACE2-mediated endocytosis, underscoring its potential in antiviral research. Compared to conventional gene knockouts or chemical inhibitors, RIVET offers unmatched temporal resolution without off-target effects or irreversible perturbations, making it ideal for dissecting the dynamic transport systems in cells. The technology has been widely validated across multiple transport pathways and model systems and has been published in the high-impact journal Advanced Science. RIVET represents a significant advancement in the toolkit for cell biology and opens new avenues for developing therapies targeting trafficking-related diseases such as neurodegeneration, developmental disorders, and viral infections. |
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https://advanced.onlinelibrary.wiley.com/doi/full/10.1002/advs.202405568 |
其他參考資料 Related Information |
清大首頁故事 https://www.nthu.edu.tw/hotNews/content/1202 元氣網報導 https://health.udn.com/health/story/5999/8461557 工商時報報導 https://www.ctee.com.tw/news/20241231701227-431401 自由時報報導 https://health.ltn.com.tw/article/breakingnews/4909181 清華首頁故事(英) https://nthu-en.site.nthu.edu.tw/p/406-1003-281770.php Associated Press Yahoo! Finance https://finance.yahoo.com/news/nthu-develops-cellular-transport-freeze-180000026.html?guccounter=1 MorningStar Benzinga Fox 40 GlobeNewswire Toronto Sun Vancouver Sun Financial Post Ottawa Citizen Calgary Herald The Province The Manila Times Windsor Star StreetInsider The Winnipeg Sun Regina Leader-Post The StarPhoenix Canoe.Com Calgary Sun |