COVER STORY
真知印記
作為研究型大學，陽明與Nature期刊淵源深厚。從參與人類、黑猩猩與水稻基因體定序，到謝世良教授團隊對登革熱致死機制的研究，以至於2019年楊慕華副校長的頭頸癌轉移機轉研究，陽明持續在此頂尖期刊及其系列刊物留下真知的印記。
以下所列為2015年至2019年間陽明大學師生刊登於《自然》及其系列期刊的研究者。展出現場特別撥放十餘位曾發表文章於NATURE及其系列期刊的研究者，現身談談自身研究的訪談影片，精彩不可錯過，請至展覽現場聆賞。
- 人文與社會科學院人文與社會教育中心 張立鴻
- 人文與社會科學院心智哲學研究所 嚴如玉
- 生命科學院生化暨分子生物研究所 王琬菁
- 生命科學院神經科學研究所 陳摘文
- 生命科學院生化暨分子生物研究所 姜為中
- 生命科學院生化暨分子生物研究所 張崇德
- 生命科學院生化暨分子生物研究所 張智芬
- 生命科學院生化暨分子生物研究所 陳威儀
- 生命科學院生命科學系暨基因體科學研究所 李曉暉
- 生命科學院生命科學系暨基因體科學研究所 周記源
- 生命科學院神經科學研究所 林士傑
- 生命科學院神經科學研究所 劉福清
- 生命科學院微生物及免疫學研究所 林奇宏
- 生命科學院微生物及免疫學研究所 陳念榮
- 生命科學院微生物及免疫學研究所 蔡明翰
- 生物醫學暨工程學院生物醫學工程學系 江明彰
- 生物醫學暨工程學院生物醫學影像暨放射科學系 莊惠燕
- 生物醫學暨工程學院生醫光電研究所 邱爾德
- 生物醫學暨工程學院醫學生物技術暨檢驗學系 黃尉倫
- 腫瘤惡化卓越研究中心 陳建鋒
- 醫學院生物醫學資訊研究所 巫坤品
- 醫學院急重症醫學研究所 許瀚水
- 醫學院腦科學研究所 楊智傑
- 醫學院腦科學研究所 蔡金吾
- 醫學院腦科學研究所 鄭菡若
- 醫學院臨床醫學研究所 李光申
- 醫學院臨床醫學研究所 周德盈
- 醫學院臨床醫學研究所 陳斯婷
- 醫學院臨床醫學研究所 楊慕華
- 醫學院醫學系 王署君
- 醫學院醫學系 洪榮志
- 醫學院醫學系 莊其穆
- 醫學院醫學系 陳志強
- 醫學院醫學系 陳適安
- 醫學院醫學系 戴世光
- 藥物科學院生物藥學研究所 李利
- 藥物科學院生物藥學研究所 黃奇英
周記源 Chi-Yuan Chou
Volume 518 Issue 7537, 5 February 2015
Structure and function of a novel single-chain, multi-domain long-chain acyl-CoA carboxylase
Abstract
Biotin-dependent carboxylases are widely distributed in nature and have important functions in the metabolism of fatty acids, amino acids, carbohydrates, cholesterol and other compounds1,2,3,4,5,6. Defective mutations in several of these enzymes have been linked to serious metabolic diseases in humans, and acetyl-CoA carboxylase is a target for drug discovery in the treatment of diabetes, cancer and other diseases7,8,9. Here we report the identification and biochemical, structural and functional characterizations of a novel single-chain (120 kDa), multi-domain biotin-dependent carboxylase in bacteria. It has preference for long-chain acyl-CoA substrates, although it is also active towards short-chain and medium-chain acyl-CoAs, and we have named it long-chain acyl-CoA carboxylase. The holoenzyme is a homo-hexamer with molecular mass of 720 kDa. The 3.0 Å crystal structure of the long-chain acyl-CoA carboxylase holoenzyme from Mycobacterium avium subspecies paratuberculosis revealed an architecture that is strikingly different from those of related biotin-dependent carboxylases10,11. In addition, the domains of each monomer have no direct contact with each other. They are instead extensively swapped in the holoenzyme, such that one cycle of catalysis involves the participation of four monomers. Functional studies in Pseudomonas aeruginosa suggest that the enzyme is involved in the utilization of selected carbon and nitrogen sources.
https://www.nature.com/articles/nature13912
陳摘文 Tsai-Wen Chen
Volume 519 Issue 7541, 5 March 2015
A motor cortex circuit for motor planning and movement
Abstract
Activity in motor cortex predicts specific movements seconds before they occur, but how this preparatory activity relates to upcoming movements is obscure. We dissected the conversion of preparatory activity to movement within a structured motor cortex circuit. An anterior lateral region of the mouse cortex (a possible homologue of premotor cortex in primates) contains equal proportions of intermingled neurons predicting ipsi- or contralateral movements, yet unilateral inactivation of this cortical region during movement planning disrupts contralateral movements. Using cell-type-specific electrophysiology, cellular imaging and optogenetic perturbation, we show that layer 5 neurons projecting within the cortex have unbiased laterality. Activity with a contralateral population bias arises specifically in layer 5 neurons projecting to the brainstem, and only late during movement planning. These results reveal the transformation of distributed preparatory activity into movement commands within hierarchically organized cortical circuits.
姜為中 Wei-Chung Chiang,
Volume 558 Issue 7708, 7 June 2018
Disruption of the beclin 1-BCL2 autophagy regulatory complex promotes longevity in mice
Abstract
Autophagy increases the lifespan of model organisms; however, its role in promoting mammalian longevity is less well-established1,2. Here we report lifespan and healthspan extension in a mouse model with increased basal autophagy. To determine the effects of constitutively increased autophagy on mammalian health, we generated targeted mutant mice with a Phe121Ala mutation in beclin 1 (Becn1F121A/F121A) that decreases its interaction with the negative regulator BCL2. We demonstrate that the interaction between beclin 1 and BCL2 is disrupted in several tissues in Becn1F121A/F121A knock-in mice in association with higher levels of basal autophagic flux. Compared to wild-type littermates, the lifespan of both male and female knock-in mice is significantly increased. The healthspan of the knock-in mice also improves, as phenotypes such as age-related renal and cardiac pathological changes and spontaneous tumorigenesis are diminished. Moreover, mice deficient in the anti-ageing protein klotho3 have increased beclin 1 and BCL2 interaction and decreased autophagy. These phenotypes, along with premature lethality and infertility, are rescued by the beclin 1(F121A) mutation. Together, our data demonstrate that disruption of the beclin 1-BCL2 complex is an effective mechanism to increase autophagy, prevent premature ageing, improve healthspan and promote longevity in mammals.