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Research

Endolysosomal ion channels

We used to look up at the sky and wonder at our place in the stars.

-- Cooper <Interstellar>

      你可曾仰望星空,好奇那些星星上面會有怎樣的風景? 內溶酶體就像是細胞宇宙內的點點繁星,散落聚合移動各有其目的與使命,而本實驗室的核心技術Endo-lysosomal patch-clamp technique與細胞內鈣訊號分析,好比阿波羅登月小艇登陸月球與哈伯望遠鏡探望深空,能直接紀錄細胞內最微小的胞器-內溶酶體,其膜表面離子通道所產生的訊號。

      內溶酶體系統,又稱為內-溶小體系統(Endo-lysosomal system),由細胞內最微小的胞器囊泡們所組成,負責掌管細胞內物質的進出、代謝及自噬(Autophagy)、與維持細胞內環境的恆定(Homeostasis)。內溶酶體系統相當於細胞內的消化兼循環系統,掌管著細胞的生理與病理機制。而存在於其中的離子通道,已知能藉由調控胞器內外離子的進出,直接地影響內溶酶體的功能。而近年隨著內溶酶體膜片箝制技術與高解析度細胞內鈣訊號技術的誕生,人們能直接測量這些細胞內胞器離子通道的活性,使其成為精準醫療的潛在新興藥物標靶。

The Endolysosomal system is composed of the smallest organelle vesicles in the cell, involving multiple cell functions via regulating intracellular trafficking, metabolism, homeostasis, and autophagy. The ion channels are implicated to directly affect the function of endolysosomes by controlling the ion flows across the endolysosomal membrane. Recently, the novel whole-endolysosomal patch-clamp technique has enabled the direct measurement of endolysosomal ion channel activity for the first time, which increases our understanding of the pathophysiological role of these channels in human disease. 

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