Core Connection: Electron Microscopy

October 23, 2017 | by Katie Neith

Electron_Microscopy | City of Hope Surface structure of a monocyte
To understand, treat and defeat diseases like cancer and diabetes, scientists must gain a deep knowledge of the building blocks of biological life. At City of Hope’s Electron Microscopy Core Facility, researchers can take sharper, closer looks at the structural elements that form the human body at the nanoscale.
The facility includes several electron microscopes, which use a beam of accelerated electrons to illuminate and create an image of a sample, and an atomic force microscope, a type of scanning probe microscopy, which forms images of surfaces using a physical probe that scans the specimen. Both types of instruments provide imaging at far greater resolution than light microscopy, allowing ultra-fine details of individual cells to be revealed and macromolecular structures to be solved.
City of Hope’s Electron Microscopy (EM) Core is exceptionally well-equipped, with specialists who can assist with many types of specimen preparation. One service particularly relevant to projects at City of Hope is preparation of samples for 3D quantitative ultrastructural analysis. Investigators apply these methods to learn the metabolic state of cells under a variety of conditions, and they are especially valuable when combined with “molecular tags” to localize certain molecules within ultra-fine cell structures that can only be observed with an electron microscope or to localize nanoparticles being investigated as tools for cancer drug delivery. The EM Core is also one of a few labs in the country that can perform serial blockface 3D electron microscopy.
In addition, core members can preserve the ultra-fine structure of tissues and cells using the latest cryofixation methods such as high-pressure freezing and freeze substitution methods. They can also prepare macromolecules using state-of-the-art cryo-EM to view specimens under ultralow temperature conditions. The aim of this freezing method is to minimize structural distortions otherwise inherent in preparative methods for electron microscopy. Cryo-EM has revolutionized how the structure of molecules are solved and its importance has been made clear by the 2017 Nobel Prize in Chemistry being awarded to the scientists originating this elegant technique.
While sample preparation, data collection, and imagine analysis are the key resources that the EM Core provides, the expert staff also provide training for researchers who want to learn how to do their own sample preparation and/or how to operate both electron and atomic force microscopes.
“The EM Core is in an enviable position in being able to assist in testing hypotheses in a variety of projects brought to the core by City of Hope investigators,” said Marcia Miller, Ph.D., director of the Electron Microscope Core. “The three of us in the core — Manager Zhuo Li, Ph.D., Staff Scientist Ricardo Zerda, and myself — draw on our diverse training and experience to assist in the design and completion of experiments.”
Recent projects that utilized the services of the EM Core include projects on developing better means for delivering drugs to kill cancer cells, developing more sensitive imaging techniques for detecting breast cancer, learning more about how to grow insulin-producing cells in the laboratory so that they might be used to treat type I diabetes, and efforts to minimize serious side effects that sometimes occur in hematopoietic stem cell transplantation for the treatment of lymphoma and leukemia.
City of Hope and Beckman Research Institute of City of Hope offer nearly 30 shared resources to meet researchers’ needs for specialized equipment, services or expert consultation — crucial tools for the pursuit of new treatments and potential cures. These core services, including the Electron Microscopy Core, are key to City of Hope’s status as a National Cancer Institute-designated comprehensive cancer center and serve as resources for the greater Southern California research community.
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