Towards Single Molecule Structural Cell Biology with Cryo-EM
Event Details
- Type
- Evnin Chemical and Structural Biology Seminar Series
- Speaker(s)
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Bronwyn Lucas, Ph.D., assistant professor of biochemistry, biophysics and structural biology, Center for Computational Biology, University of California, Berkeley
- Speaker bio(s)
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Abstract: Cryogenic electron tomography (cryo-ET) is revolutionizing cell and structural biology by visualizing macromolecular structure in the native cell context. However, confident annotation of single molecules is not possible in tomograms, limiting application of this technique to a few massive and highly abundant complexes. The Lucas Lab are developing an alternate strategy in which they use existing structures as high-resolution templates to locate and orient single molecules in cryo-EM images (rather than tomograms) of cells. They show that 2D template matching (2DTM) can be used to classify related complexes with single molecule probabilities and generate high-resolution in situ reconstructions without model bias. To support further development of this approach they have built Leopard-EM, an extensible Python-based software architecture for rapid development of new methods.
Dr. Lucas will demonstrate how her lab have applied Leopard-EM to improve detection of small ribosomal subunits and capture single molecule dynamics of ribosome rotation during translation in cells. She will additionally describe the development of a new method called molecular in situ atomic coordinate scan (MOSAICS) to probe molecular structure in situ that requires two orders of magnitude fewer particles than 3D reconstruction, extending structural analysis to rare complexes. The field of structural biology has entered a new era analogous to that of genomics at the turn of the century. Improved accuracy in structure prediction has made it possible to generate a reference 'structureome' from genomic sequences. 2DTM and MOSAICS are single molecule tools for the new ‘structureomic’ era that can leverage these databases to visualize molecular networks in cells and study the molecular biology of the cell… in the cell.
- Open to
- Tri-Institutional