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UT Southwestern’s New Microscope Center Zooms In On The Unknown

Breakthroughs.KERA.org 41

UT Southwestern Medical Center just opened a $17 million microscope center – not the kind we used in science class, but super-powered microscopes. Michael Rosen with UT Southwestern talks about what these microscopes will find.

The KERA radio interview

Interview Highlights: Michael Rosen …

… on the equipment at the new center: “Two of them are what are called cryo-electron microscopes. These are very powerful microscopes that allow us to study essentially proteins and cells at very high levels of resolution. The third piece of equipment — that is something that is more unique. Many places have cryo-electron microscopes. The third piece is something called a focused ion beam mill or a ‘cryoFIB mill’. That allows us to essentially take a sample that is normally too big to analyze with cryoEM [and] mill it down — essentially sandblast away parts of the sample — so we have a very thin wafer that we can then analyze.”

… on how the cryoEM microscopes compare to others: “When most people think microscopes, I think they think of a light microscope. That is you use light waves to irradiate a sample with it, and you observe this sample with normal light. Electron microscopes is a similar idea, but instead of using light, you use electrons. Those can then penetrate, those can then give you much, much higher resolution than light can.”

With the opening of UT Southwestern’s new cryo-electron microscope facility, researchers can now view 3D images of objects as tiny as an atom to intact cells like the propelling tail of a sea urchin sperm cell shown in this video. The work may provide insight on how to develop more effective treatments for particular human lung and other diseases. (This video appears courtesy of the Nicastro lab)

https://vimeo.com/165437722/d335c3b062

… on the size of the new microscopes: “These microscopes are enormous. One of our microscopes stands about 14 feet tall. It has a 6×6 footprint. It weighs a couple of thousand pounds and sucks through huge amounts liquid nitrogen to keep it cold because all of the samples are analyzed at liquid nitrogen temperatures, several hundred degrees below zero. The reason you have to do that is that you have to freeze your samples in a way that ice crystals don’t form. If you slowly cool your samples down, the water in them will crystallize and that will essentially destroy cells; it will wreck molecules. If you so-called ‘flash freeze’ them … the water molecules essentially freeze where they are without forming long crystals.”

… on the potential for the new center: “I think there are going to be a lot of discoveries. The idea is that we can study essentially vast swaths of basic biology. We can study how proteins work to transmit information across the cell membrane. We can study how proteins work to get molecules from one place to another; for example, from inside the nucleus to outside the nucleus, we can understand how molecules come together to create metabolic pathways. All of those are really of the essence of basic biology. I give you an example from a new faculty member, Xiao-chen Bai. We just recruited him into biophysics and cell biology; he’ll be arriving in December. Xiao-chen is interested in a family of proteins called transmembrane receptors. The basic idea is these are proteins that sit in the outer membrane of the cell, they bind to molecules outside of the cell; for example, there are some that bind insulin, and they transmit that binding inside the cell to cause the cell to change itself, to express different genes, to divide. … And what Xiao-chen is going to try to understand is how that transmission occurs across the membrane. We understand how the binding outside works, we understand some of the inside mechanisms. But that key question — how do you transmit something across the outer membrane of a cell — remains very poorly understood. So Xiao-chen’s research program is focused on using cryoelectron-microscopy to understand this key question, and those transmembrane receptors are essentially found (in) many different types on all cells in the human body. That will impact our understanding almost anywhere in biology.”

Michael Rosen is the chair of the department of biophysics at UT Southwestern.