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CCB-MCB Seminar: “Single molecule localization and structure probing in cells” – Bronwyn Lucas (University of Massachusetts Medical School)
February 9 @ 11:00 am - 12:00 pm
Speaker: Bronwyn Lucas, Senior Research Scientist (University of Massachusetts Medical School)
Title: “Single molecule localization and structure probing in cells”
Date and Time: Wednesday, February 9, 11AM-NOON
SEMINAR ZOOM LINK:
Meeting ID: 912 0440 3367
“Single molecule localization and structure probing in cells”
Cryo-electron microscopy (cryo-EM) has become the main technique delivering atomic structures of a diverse range of molecules. In parallel, machine learning algorithms are more successfully predicting protein structures from their amino acid sequences. These developments will eventually establish protein structure determination as a routine process, much like cloning a gene. The focus of structural biology has therefore begun to shift to understanding how molecules work together to realize the plethora of biological processes inside cells, tissues and organisms. However, existing approaches have difficulty localizing all but the most abundant complexes and are insufficiently sensitive to characterize small, but functionally important differences between molecules in the cell. I am using 2D template matching (2DTM), a method co-developed in the Grigorieff lab, to leverage the growing library of high-resolution structures to locate unlabeled macromolecules in cryo-EM images of frozen cells using their atomic structures as a unique identifier. I have extended 2DTM to characterize how the structure of molecules in the cell deviates from in vitro determined structures. I have used this approach, which I call molecular in situ atomic coordinate scan (MOSAICS), to map distinct stages in ribosomal biogenesis within the cell nucleus. Together, 2DTM and MOSAICS represent new approaches for the “post-structural era” that will allow interrogation of complex, multistep biological processes within cells at the level of single molecules. In my own lab I will further develop MOSAICS and apply it to examine ribosome assembly and heterogeneity within and between cells.
Bronwyn has an undergraduate degree in Biochemistry and Molecular Biology from the University of Adelaide, Australia and a PhD in RNA Molecular Biology from the University of Rochester, New York. As a PhD student she used bioinformatic and molecular tools to study the regulation of mRNA turnover by repetitive elements. After her PhD she realized that cryo-EM could be applied to the kinds of molecular biology questions that she was interested in, within the context of the cell. To pursue this she joined Niko Grigorieff’s lab at Janelia Research Campus as a postdoc where she initiated cryo-FIB milling in the lab and developed new approaches for using high-resolution template matching to interrogate populations of molecules in cells. She followed Niko to UMass Medical School in 2021, now as a senior research scientist and co-PI on a Chan Zuckerberg Initiative grant, where she leads efforts to further develop and apply methods to use cryo-EM to study molecular populations in cells.