【神经科学前沿技术培训系列】详见文末
导言
Bio-protocol和逻辑神经科学将在金秋季节隆重推出线上“生命科学研究前沿技术论坛系列”,专注于生命科学技术的最新进展,重点探讨前沿技术、方法和工具的实际应用。论坛将邀请国内外杰出的科学家和技术专家,与广大研究人员共同分享、学习,并深入讨论如何将这些新技术和工具更好地应用于各个研究领域。
我们非常荣幸邀请到陈良怡教授(北京大学)担任首场成像专题(第1期)主讲嘉宾,并由席鹏教授(北京大学)、李博研究员(复旦大学)和冯倩倩高级工程师(清华大学)作为互动嘉宾共同参与本次网络研讨会。
专题亮点
2. 利用双模式显微镜技术,全面成像细胞器及分子相互作用。
3. 创新两步迭代去卷积算法,突破活细胞SR成像的分辨率极限,成功捕捉核孔动态变化。
4. 开发背景去除新技术,实现活细胞SR成像的定量分析与大分子结构精准研究。
摘要
向上滑动阅览
Here we present an overview of our recent works in live-cell superresolution (SR) microscopy. Over the past ten years, we have developed several innovative techniques to improve the resolution and accuracy of live-cell imaging.
Our first breakthrough was the development of a structured illumination microscopy technique based on the continuity of biological structures embedded in Hessian matrices (Hessian-SIM). Hessian-SIM significantly reduces the photon dosage required for SR microscopy while suppressing reconstruction artifacts induced by random noise. Additionally, we demonstrated that the high sensitivity of this method allows for the use of sub-millisecond excitation pulses followed by dark recovery times, reducing photobleaching and enabling hour-long time-lapse SR imaging with common fluorescent probes in live cells (Nat. Biotechnol. 2018).
To enable holistic SR imaging, we developed a dual-mode microscopy technique that combines SIM with label-free three-dimensional optical diffraction tomography (ODT). By providing a holistic view of organelles and simultaneously highlighting molecules, this method is ideal for studying organelle interactomes. We demonstrated that the ODT module can resolve mitochondria, lipid droplets, the nuclear membrane, chromosomes, the tubular endoplasmic reticulum, and lysosomes (Light Sci Appl. 2020).
To further push the resolution limit of live-cell SR imaging, we developed a two-step iterative deconvolution algorithm based on continuity and sparsity of fluorescence signals (Sparse deconvolution), which extends resolutions beyond the physical limits of optical systems. Sparse-SIM achieving ~60 nm resolution at a 564 Hz frame rate, resolving dynamics of ring-shaped nuclear pores over an hour in live cells. The algorithm can also be used to improve resolutions of other fluorescence microscopes, such as confocal, STED, and lightsheet microscopes. Thus this mathematical path to improve microscopic resolution may have broad implications (Nat. Biotechnol. 2022).
Finally, for live-cell SR imaging to be quantitative, the completeness of delicate structures and the linearity of fluorescence signals are required in addition to resolution. To make live-cell SIM microscopy more quantitative, we proposed a physical model-based background removal method (BF-SIM). BF-SIM preserves intricate and weak structures down to sub-70 nm resolution while maintaining signal linearity, enabling us to discover novel, dynamic actin structures in live cells (Nat. Commun. 2023).
报名方式
扫描上方二维码或点击“阅读原文”即可报名,首场成像专题(第1期)将于北京时间2024年10月10日20:00-21:00正式开启。同时您可按照提示提前向专家们提出您的问题,他们将选择一些共通的疑问在研讨会直播时为您解答。欢迎大家积极提问!
主讲嘉宾
陈良怡,北京大学博雅特聘、长聘教授,新基石研究员。北京大学国家生物医学成像科学中心副主任,获得国家自然科学基金委杰出青年基金等资助,是科技部重点研发专项、基金委重大研究计划集成项目的首席科学家。为了在不同的时空尺度研究糖尿病相关的胰岛素分泌调控,发明一系列的高时空分辨率生物医学成像的可视化手段,包括高分辨率微型化双光子显微镜,海森结构光超分辨显微镜,活细胞双模态超分辨率显微镜,发明基于新数学原理的稀疏解卷积超分辨率成像算法,实现活细胞成像中分辨率最高(60nm)、速度最快(564Hz)、成像时间最长(>1小时),也能够实现跨尺度多模态超分辨提升。工作获得“2021、2023年度中国光学领域十大社会影响力事件(Light10)”等奖励,并两次入选国家“十三五”科技创新成就展;商品化超分辨率显微镜和微型化双光子销往国内顶级科研机构,解决高端显微镜的卡脖子问题,2022年销售过亿元,完成从基础理论创新-新技术方法-生物医学应用-商业转化-推动领域前进从而产生社会价值的闭环。
互动嘉宾
(按拼音顺序排列)
冯倩倩 清华大学 高级工程师
席鹏 北京大学 教授
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