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重要研究成果

賴品光 博士
(2020)
Jasper Che-Yung Chien, Elie Tabet, Kelsey Pinkham, Cintia Carla da Hora, Jason Cheng-Yu Chang, Steven Lin, Christian E. Badr* and Charles Pin-Kuang Lai*
Nucleic Acids Research, doi: 10.1093/nar/gkaa669 (2020).
本研究題目A multiplexed bioluminescent reporter for sensitive and non-invasive tracking of DNA double strand break repair dynamics in vitro and in vivo的代表性圖片
Tracking DNA double strand break (DSB) repair is paramount for the understanding and therapeutic development of various diseases including cancers. Herein, we describe a multiplexed bioluminescent repair reporter (BLRR) for non-invasive monitoring of DSB repair pathways in living cells and animals. The BLRR approach employs secreted Gaussia and Vargula luciferases to simultaneously detect homology-directed repair (HDR) and non-homologous end joining (NHEJ), respectively. BLRR data are consistent with next-generation sequencing results for reporting HDR (R2 = 0.9722) and NHEJ (R2 = 0.919) events. Moreover, BLRR analysis allows longitudinal tracking of HDR and NHEJ activities in cells, and enables detection of DSB repairs in xenografted tumours in vivo. Using the BLRR system, we observed a significant difference in the efficiency of CRISPR/Cas9-mediated editing with guide RNAs only 1–10 bp apart. Moreover, BLRR analysis detected altered dynamics for DSB repair induced by small-molecule modulators. Finally, we discovered HDR-suppressing functions of anticancer cardiac glycosides in human glioblastomas and glioma cancer stem-like cells via inhibition of DNA repair protein RAD51 homolog 1 (RAD51). The BLRR method provides a highly sensitive platform to simultaneously and longitudinally track HDR and NHEJ dynamics that is sufficiently versatile for elucidating the physiology and therapeutic development of DSB repair.
賴品光 博士
(2020)
Anthony Yan-Tang Wu, Yun-Chieh Sung, Yen-Ju Chen, Steven Ting-Yu Chou, Vanessa Guo, Jasper Che-Yung Chien, John Jun-Sheng Ko, Alan Ling Yang, Hsi-Chien Huang, Ju-Chen Chuang, Syuan Wu, Meng-Ru Ho, Maria Ericsson, Wan-Wan Lin, Chantal Hoi Yin Cheung, Hsueh-Fen Juan, Koji Ueda, Yunching Chen, Charles Pin-Kuang Lai*
Advanced Science, doi:/10.1002/advs.202001467 (2020).
本研究題目Multiresolution Imaging Using Bioluminescence Resonance Energy Transfer Identifies Distinct Biodistribution Profiles of Extracellular Vesicles and Exomeres with Redirected Tropism的代表性圖片
Extracellular particles (EPs) including extracellular vesicles (EVs) and exomeres play significant roles in diseases and therapeutic applications. However, their spatiotemporal dynamics in vivo have remained largely unresolved in detail due to the lack of a suitable method. Therefore, a bioluminescence resonance energy transfer (BRET)‐based reporter, PalmGRET, is created to enable pan‐EP labeling ranging from exomeres (<50 nm) to small (<200 nm) and medium and large (>200 nm) EVs. PalmGRET emits robust, sustained signals and allows the visualization, tracking, and quantification of the EPs from whole animal to nanoscopic resolutions under different imaging modalities, including bioluminescence, BRET, and fluorescence. Using PalmGRET, it is shown that EPs released by lung metastatic hepatocellular carcinoma (HCC) exhibit lung tropism with varying distributions to other major organs in immunocompetent mice. It is further demonstrated that gene knockdown of lung‐tropic membrane proteins, solute carrier organic anion transporter family member 2A1, alanine aminopeptidase/Cd13, and chloride intracellular channel 1 decreases HCC‐EP distribution to the lungs and yields distinct biodistribution profiles. It is anticipated that EP‐specific imaging, quantitative assays, and detailed in vivo characterization are a starting point for more accurate and comprehensive in vivo models of EP biology and therapeutic design.
汪治平 博士
(2020)
Zan Nie, Chih-Hao Pai, Jie Zhang, Xiaonan Ning, Jianfei Hua, Yunxiao He, Yipeng Wu, Qianqian Su, Shuang Liu, Yue Ma, Zhi Cheng, Wei Lu1, Hsu-Hsin Chu, Jyhpyng Wang, Chaojie Zhang, Warren B. Mori, and Chan Joshi
Nature Communication 11, 2787 (2020)
Availability of relativistically intense, single-cycle, tunable infrared sources will open up newareas of relativistic nonlinear optics of plasmas, impulse IR spectroscopy and pump-probeexperiments in the molecular fingerprint region. However, generation of such pulses is still achallenge by current methods. Recently, it has been proposed that time dependent refractiveindex associated with laser-produced nonlinear wakes in a suitably designed plasma densitystructure rapidly frequency down-converts photons. The longest wavelength photons slipbackwards relative to the evolving laser pulse to form a single-cycle pulse within the nearlyevacuated wake cavity. This process is called photon deceleration. Here, we demonstrate thisscheme for generating high-power (~100 GW), near single-cycle, wavelength tunable(3–20 μm), infrared pulses using an 810 nm drive laser by tuning the density profile of theplasma. We also demonstrate that these pulses can be used to in-situ probe the transient andnonlinear wakes themselves.
謝雅萍 博士
(2020)
Heming Yao, Ya-Ping Hsieh, Jing Kong and Mario Hofmann
Nature Materials, 19, 745–751 (2020).
本研究題目Modelling electrical conduction in nanostructure assemblies through complex networks的代表性圖片
Carrier transport processes in assemblies of nanostructures rely on morphology-dependent and hierarchical conduction mechanisms, whose complexity cannot be captured by current modelling approaches. Here we apply the concept of complex networks to modelling carrier conduction in such systems. The approach permits assignment of arbitrary connectivity and connection strength between assembly constituents and is thus ideal for nanostructured films, composites and other geometries. Modelling of simplified rod-like nanostructures is consistent with analytical solutions, whereas results for more realistic nanostructure assemblies agree with experimental data and reveal conduction behaviour not captured by previous models. Fitting of ensemble measurements also allows the conduction properties of individual constituents to be extracted, which are subsequently used to guide the realization of transparent electrodes with improved performance. A global optimization process was employed to identify geometries and properties with high potential for transparent conductors. Our intuitive discretization approach, combined with a simple solver tool, allows researchers with little computational experience to carry out realistic simulations.
廖仲麒 博士
(2020)
eLife 9, e53580 (2020).
本研究題目Super-resolution microscopy reveals coupling between mammalian centriole subdistal appendages and distal appendages的代表性圖片
Subdistal appendages (sDAPs) are centriolar elements observed proximal to the distal appendages (DAPs) in vertebrates. Despite their obvious presence, structural and functional understanding of sDAPs remains elusive. Here, by combining super-resolved localization analysis and CRISPR-Cas9 genetic perturbation, we find that, although DAPs and sDAPs are primarily responsible for distinct functions in ciliogenesis and microtubule anchoring respectively, the presence of one element actually affects the positioning of the other. Specifically, we find dual layers of both ODF2 and CEP89, where their localizations are differentially regulated by DAP and sDAP integrity. DAP depletion relaxes longitudinal occupancy of sDAP protein ninein to cover the DAP region, implying a role of DAPs in sDAP positioning. Removing sDAPs alter the distal border of centrosomal γ-tubulins, illustrating a new role of sDAPs. Together, our results provide an architectural framework of sDAPs to shed light on functional understanding, surprisingly revealing the coupling between DAPs and sDAPs.
 
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