2021-01-012024-05-18https://scholars.lib.ntu.edu.tw/handle/123456789/713604"細胞膜是由蛋白質與脂質構成、作為細胞與外界環境屏障與溝通的重要胞器。研究細胞膜的動態調控這一科學，需要生化學、細胞生物學以及生物物理學的知識與技術。 我與法國CNRS研究員蔡鳳卿博士是在2013年法國舉辦的細胞膜重塑會議上認識。蔡博士是物理背景出身，因此與生物學出身的我在研究細胞膜調控上有共同的研究興趣以及完美的專業互補。因此，與蔡博士的合作將能補強我學術研究的一大弱項-生物物理學；而我實驗室的專長-細胞生物學以及活細胞影像，將能與蔡博士的生物物理團隊有完美的互補，相信我們未來不但能互相補強彼此學術研究的弱項，更能相互學習成長為跨領域的研究人員，並且締造台法雙邊合作的成果。 我們希望藉著幽蘭計畫進行兩年的合作研究、交流訪問，未來能與蔡博士建立長期且多方面的雙邊合作。 我們的研究主題為 “SNX9蛋白在血小板生長因子誘發大胞飲作用中的生化與物理機制”。我們與法方團隊將分別利用細胞生物學之細胞活細胞4D影像系統，以及生物物理學之重組生物學與數學模型預測研究此一對病毒感染、訊息傳遞以及癌細胞生長非常重要的細胞現象¬-大胞飲作用。 我們的預期效益為:建立我實驗室與法國CNRS, Institut Curie,物理化學實驗室-細胞膜與生物功能團隊雙邊長期交流合作，並透過互訪以及舉辦研討會與工作坊，帶領雙邊研究單位更多研究員的交流與合作。我相信這個合作不但會有實質的研究論文產出，隨著兩方研究員、老師與學生的互相訪問與認識，也將促進台大與Institut Curie的多方面認識與合作。" Macropinocytosis, occurring on the plasma membrane of cells, is an efficient way for the cells to ingest extracellular materials such as antigens and nutrients through endocytic vesicles called macropinosomes. Notably, macropinocytosis is exploited by numerous types of cancer cells to take up nutrients, and by certain bacteria and viruses to invade host cells. Yet, despite the importance of macropinocytosis in cell viability and pathology, the mechanisms underlying macropinosome formation remain elusive. Mechanistically, macropinosome formation begins with forming sheet-like membrane protrusions called ruffles . The main driving force for ruffle formation is the actin cytoskeleton, more specifi-cally the Arp2/3 complex-mediated branched actin network. During macropinocytosis, membrane ruffles are extended linearly into finger-like shape, or circularly into cup-like shape. Then, the ruffles are curved, fused, and finally undergone fission, leading to the formation of macropinosomes. It must note that during this process, the shape of ruffles’ membrane, thus the corresponding membrane curvature, undergoes drastic, yet restricted, change. So far, it remains unclear how the reshaping of membrane ruffles is spatiotemporally controlled to form macropinosomes. We hypothesize that SNX9 is a key membrane environment sensor and actin modulator in membrane ruffle formation during macropinocytosis. This project aims to elucidate the molecular and physical mechanisms of SNX9-actin driven ruffle for-mation in macropinocytosis.細胞膜重塑4D活細胞影像生物物理學大胞飲作用Membrane remodeling4D live cell imagingbiophysicsmacropinocytosis