A Comprehensive Cancer Center Designated by the National Cancer Institute

Pathways to Discovery: Winter 2014

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Focus on: Core Facilities
Integrated Microscopy Core Facility Provides Tools for Top Science

Many discoveries have been made by scientists looking through a microscope, beginning with early users Galileo Galilei, Robert Hooke, and Anton van Leeuwenhoek in the 17th century. Researchers still use microscopes to study how cells behave, but both the power of magnification and resolution of modern-day microscopes have increased to unprecedented levels. Now, microscopy increases our capability of seeing detail by 10,000 times so that objects as small as nanometers can be visualized.

According to Vytas Bindokas, PhD, technical director of the Integrated Microscopy Core Facility, the field continues to advance, with new types of microscopy tools pushing the limit in innovation. “Modern optics have surpassed the diffraction limit, which means we are now seeing objects smaller than anyone had previously thought possible using light.”

To help scientists at the University of Chicago Medicine Comprehensive Cancer Center stay abreast of these advances, the Integrated Microscopy Core Facility provides a wide range of instrumentation and image-analysis tools that allow for the most advanced imaging capabilities currently available. Because this type of technology is expensive for individual laboratories to obtain on their own, and relies on expertise that takes many years to develop, the Facility and its talented staff are a rich resource for Cancer Center investigators. With instrumentation located in the Knapp Center for Biomedical Discovery and Abbott Memorial Hall, the Facility is accessible to users 24/7, with support staff available during normal business hours.

Within the past year, the Facility has announced the addition of two new systems. In late summer, they acquired a single-plane illumination microscopy system, the Zeiss LightSheet Z.1, in partnership with the Institute for Genomics & Systems Biology. This microscope utilizes a sheet of light through which the specimens move, producing a thin optical slice that is 2-10 microns thick. Christine Labno, PhD, co-technical director, said the camera-based system uses low-intensity laser light, which is gentle on the samples. It is well-suited to capture time-lapse imaging of larger living organisms, such as zebrafish, Drosophila (fruit fly) embryos, C. elegans (a type of worm), and small plants. The system can capture cyan, green, and/or red signals at very high detail and very high speed. The technology has also been used to image living and fixed 3-D cell cultures, including organoids, cysts, and 3-D cell migration assays to study cell migration and development.

The other instrument, which was purchased in November by the Institute for Genomics & Systems Biology, is the Leica Super-resolution 3-D Ground State Depletion system. This wide-field fluorescent microscope captures the images of individual molecules in two to three colors. In just a couple of minutes, the image is formed from these colored dots, similar to the “pointillist” technique. In addition, this microscope achieves lateral resolution down to 20 nanometers and vertical spatial resolution to 50 nanometers, which is nearly ten times better than confocal microscopy. Therefore, the system helps researchers visualize the 3-D location of molecules and structures at a level never possible before to better understand cellular processes. The system can localize three colors of locality maps, allowing study of interactions of diverse cellular components at molecular-level detail using light. It also features four color ultra-shallow “total internal reflection” illumination that can selectively image the points of contact of cells onto a glass coverslip. This type of illumination allows for selective study of how cells attach to surroundings and membrane events during movement, for example, metastasis of cancer cells.

With these new resources, along with the other microscopes supported by the Facility, researchers at the Cancer Center are poised to make new ground-breaking scientific discoveries.

Cancer Center members receive access to shared resources at subsidized rates. For more information on eligible core facilities, go to cancer.uchicago.edu/research/core-facilities.

 

Ernst Lengyel

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