时间：4月18日 15:00-16:30
地点：四牌楼校区榴园宾馆多功能厅
Integrated Bioimaging – A Vision Beyond the Pretty Pictures for the Quantitative 3D Architecture of Macromolecules, Organelles, Cells and Organoids
Manfred Auer
Cellular and Tissue Imaging Department, Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, USA
Biological function manifests itself (and thus needs to be understood) at the level of individual proteins, macromolecular machines, organelles, cells and tissues. Disease cannot be understood (and thus cured) without an understanding of cellular behavior and response to treatment at the tissue level. Organoids, which have been named the 2017 Method of the Year, are an excellent compromise as they are tractable but contain cells in their multicellular tissue context.
The range from macromolecules to tissues spans at least six orders of magnitude (from nanometer to millimeters), and thus cannot be imaged by a single imaging modality alone. Cross-modality and cross-scale image data integration represents one key challenge for biology imaging. Visualizing macromolecular machines and supramolecular complexes in their native cell and tissue context needs to go beyond the pretty pictures (and movies). Full utilization of imaging data will require large-volume image data acquisition followed by segmentation, annotation, volumetric model building, rigorous quantitative analysis, prototypic model generation and possibly simulation. I will submit that biological information is best integrated at the level of multiscale volumetric models, and that is is time move from –Omics-based text-string databases (the equivalent of ‘phone books’) to map-centered biospatial databases (the equivalent of ‘Google-Maps’). We start with the integration of fluorescence and 3D (focused ion beam scanning) electron microscopy through X-ray microscopy tomography, which serves as a bridging technology, that allows seamless zooming from the macroscopic to the nanoscopic scale.
I will illustrate various aspects of this vision, on which we are just beginning to embark, using examples from our research on (1) Arabidopsis thaliana plant cell wall 3D architecture obtained by cryo-tomography of vitreous sections (an 80 year old problem we recently solved), (2) mouse and chicken inner ear hair cell, underlying our senses of hearing and balance, with a focus on (cryo-)tomography of hair bundle stereocilia, as well as (3) a 3D matrix-cultured human breast cancer model system in its premalignant, malignant and dormant state, respectively. We are just beginning to use Convolutional Neural Networks for automated feature extraction and Deep (Machine) Learning for seeking ultrastructural signatures of cells and tissues, while acknowledging the heterogeneity for each of the three states.
A successful vision of a new era in cell and tissue biology imaging requires a concerted effort in cross-scale and cross-modality sample preparation, imaging, image analysis and bioimage informatics. There is no doubt that the next frontier in biology is Organoid and Tissue Biology.
