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Carolyn Larabell, PhD, Professor
carolyn.larabell@ucsf.edu
Administrative Assistant: 510-486-7105
Larabell Lab Website
Cell Biology
We are a multi-disciplinary lab addressing a range of fundamental questions in cell and developmental biology. These questions can be distilled into ‘who, what, where and when’. Which proteins are interacting during a particular event in the cell cycle, or in response to an external stimuli? What phenotypic changes occur as a result, and when? And, most importantly, where in the cell do these interactions take place? To answer these questions effectively we employ a range of techniques, in particular cellular imaging. Frequently, we have found existing imaging techniques unable to provide the information we required, and as a result we are now very active in the development of new imaging technologies. Our lab is at the forefront of developing soft x-ray tomography as a new tool for visualizing the location of proteins in cells, and for imaging sub-cellular architecture with a spatial resolution of 40nm or better. This new imaging technique combines many of the advantages of both light and electron microscopies, with characteristics unique to x-ray imaging. The 3-D tomograms obtained by this technique are in essence a CAT (Computed Axial Tomography) scan of a single cell. The images have significantly higher resolution than those produced by light microscopy, and are of intact cells (there is no need to section the cell, as is the case with electron microscopy). Consequently, this new technique produces unique insights into cell biology that can’t readily be obtained by any other imaging method.
We have designed and built the world’s first soft x-ray microscope for biomedical imaging at the Advanced Light Source, Berkeley, the worlds brightest source of x-rays in this spectral range. Currently, XM2 is capable of imaging cells at a spatial resolution of 40nm. However, recent developments in nano-fabrication have allowed the production of optical systems that can extend this resolution limit to15nm. We have developed soft x-ray tomography to be a high-throughput technique. Sufficient images to calculate a 3-D reconstruction of a cell can be recorded in three minutes or less. This allows us to image large numbers of cells in a short space of time, to generate data in quantities that are statistically meaningful.
To take full advantage of the capabilities of soft x-ray tomography, we are also developing new methods for labeling and locating specific proteins in whole cells. These labels have analogous function to the families of Fluorescent Proteins (FP) widely used in light microscopy. By labeling proteins with tags that can be visualized by both light and x-ray microscopes we can obtain correlated information that generates a more comprehensive picture than could be obtained by the use of any single imaging technique.
Professor Larabell is Director of the National Center for X-ray Tomography. For more information on her research visit http://ncxt.lbl.gov