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Advanced imaging of cellular processes across scales

日期: 2019-08-26
Topic: Advanced imaging of cellular processes across scales
Speaker:  Prof. Jan Ellenberg
the Senior Scientist and Head of che Cell Biology & Biophysics Unit at EMBL in Heidelberg
Time: 13:00-14:30, Sept. 10, 2019
Venue: Room 101,Jinguang Life Sciences Building
Host: Prof. Liangyi Chen
The recent resolution revolution in microscopy technologies allows unprecedented insights into the molecular machinery inside living systems. For the first time, imaging technologies have molecular resolving power and sensitivity and can be correlated to cover the whole range from structural detail of single molecules to imaging a whole living organism. This presentation will give examples at different scales where we have used advanced microscopy to study individual protein complexes, cellular signaling networks inside cells and aneuploidy causing cell division errors inside developing embryos.  The nuclear pore complex (NPC) is the largest macromolecular protein complex and mediates all nucleocytoplasmic transport through the nuclear envelope, each consisting of several hundred proteins. Due to this enormous size and complexity many details of its structure still remain elusive. We developed an approach that enables the reconstruction of a 3D molecular map by visualizing both scaffold and flexible nucleoporins, allowing us to address dynamic conformations and parts of the NPC that have been inaccessible for atomic resolution methods and opens the exciting possibility to observe NPC structure in different functional or assembly states. At the scale of protein networks, we established an integrated experimental and computational pipeline to build a 4D protein atlas of the dividing human cell, combining a collection of genome-edited fluorescent knock-in cell lines, absolutely quantitative live imaging and the integration and mining of this large data set by advanced bioimage analysis and machine learning. Our method is generic and makes many dynamic cellular processes now amenable to dynamic protein network analysis. At the scale of an embryo, we developed light-sheet microscopy to achieve the first in toto imaging of preimplantation mouse development from zygote to blastocyst, which was not previously possible due to their exquisite light sensitivity. We revealed when fate specification happens and that chromosome segregation is highly error prone in mouse embryos. With light-sheet microscopy, we are now able to study chromosome segregation, spindle formation and mitotic checkpoint control governing the first divisions of embryo mammalian life in real-time.
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