Manfred Auer教授学术报告


时间:4月18日 15:00-16:30


IntegratedBioimaging - A Vision Beyond the Pretty Pictures for the Quantitative 3DArchitecture of Macromolecules, Organelles, Cells and Organoids


Cellularand Tissue Imaging Department, Molecular Biophysics and Integrated BioimagingDivision, Lawrence Berkeley National Laboratory, Berkeley, USA

Biological function manifests itself (andthus needs to be understood) at the level of individual proteins, macromolecularmachines, organelles, cells and tissues. Disease cannot be understood (and thuscured) without an understanding of cellular behavior and response to treatmentat the tissue level. Organoids, which have been named the 2017 Method of theYear, are an excellent compromise as they are tractable but contain cells intheir multicellular tissue context.

The range from macromolecules to tissuesspans at least six orders of magnitude (from nanometer to millimeters), andthus cannot be imaged by a single imaging modality alone. Cross-modality andcross-scale image data integration represents one key challenge for biologyimaging. Visualizing macromolecular machines and supramolecular complexes intheir native cell and tissue context needs to go beyond the pretty pictures(and movies). Full utilization of imaging data will require large-volume imagedata acquisition followed by segmentation, annotation, volumetric modelbuilding, rigorous quantitative analysis, prototypic model generation andpossibly simulation. I will submit that biological information is bestintegrated at the level of multiscale volumetric models, and that is is timemove from –Omics-based text-string databases (the equivalent of ‘phone books’)to map-centered biospatial databases (the equivalent of ‘Google-Maps’). Westart with the integration of fluorescence and 3D (focused ion beam scanning)electron microscopy through X-ray microscopy tomography, which serves as abridging technology, that allows seamless zooming from the macroscopic to thenanoscopic scale.

I will illustrate various aspects of thisvision, on which we are just beginning to embark, using examples from ourresearch on (1) Arabidopsis thaliana plant cell wall 3D architecture obtainedby cryo-tomography of vitreous sections (an 80 year old problem we recentlysolved), (2) mouse and chicken inner ear hair cell, underlying our senses ofhearing and balance, with a focus on (cryo-)tomography of hair bundlestereocilia, as well as (3) a 3D matrix-cultured human breast cancer modelsystem in its premalignant, malignant and dormant state, respectively. We arejust beginning to use Convolutional Neural Networks for automated featureextraction and Deep (Machine) Learning for seeking ultrastructural signaturesof cells and tissues, while acknowledging the heterogeneity for each of thethree states.

A successful vision of a new era in celland tissue biology imaging requires a concerted effort in cross-scale andcross-modality sample preparation, imaging, image analysis and bioimageinformatics. There is no doubt that the next frontier in biology is Organoidand Tissue Biology.