Molecular biology department plans to bring new microscopy technique to UT

October 12, 2016

A new, higher-resolution microscope coming to UT in May 2017 will help the Department of Molecular Biosciences revolutionize its study of cellular functions.

Cryo-electron microscopy, or cryo-EM, is a method of imaging biological molecules that involves trapping particles in a thin layer of ice and shining a beam of electrons through them. The electron beam interacts with the particles to create a projection image of the sample, according to molecular biosciences professor David Taylor, a new faculty member who worked with cryo-EM for his postdoctoral research.

“This technique changes everything,” Taylor said. “I wouldn’t say easy, but it’s a generally usable technique, it’s applicable to a lot of different complexes of many different sizes and in any pathway that you can imagine.”

Light microscopy, the current method used by scientists, can only show objects about the size of 200 or 300 nanometers, but cryo-EM can show structures at three-tenths of a nanometer: that’s six times the size of an hydrogen atom. Taylor said the microscope can also show chemical reactions as they happen.

Cryo-EM can show smaller objects in greater detail than light microscopy because the wavelength of the electron beam is smaller than the wavelength of visible light, according to molecular biosciences department chair Daniel Leahy.

This ability to view structures at a more detailed level and understand the three-dimensional arrangement of atoms gives molecular biologists a better idea of how cells function, Leahy said.

“In a way, I think we’re analogous to kids growing up taking apart a clock to figure out how [it] works,” Leahy said. “In this case the clock is a cell, and the pieces of the clock are the molecules. We are essentially looking at the pieces of the cell and trying to figure out how they fit together and work to make a living cell.”

Taylor said the cryo-EM technique can help scientists study diseases caused by cellular malfunctions because it helps them understand the structure and function of cell parts and how the malfunction or mutation occurred.

Molecular bioscience professor Tanya Paull will be collaborating with Taylor to use cryo-EM for her research on MRN, a protein that repairs double-stranded DNA breaks and prevents cancerous cell development.

“We don’t have a complete picture of how [MRN] looks in the human,” Paull said. “There are a lot of structural questions we don’t have the answers to right now, and cryo-EM is really good at getting high-resolution structures of complexes.”

Before joining UT, Taylor did his postdoctoral research at UC Berkeley studying CRISPR DNA molecules, which scientists can use to edit the DNA of an organism. He used the cryo-EM imaging technique to visualize the structures of the different subtypes of CRISPR Cas systems.

The cryo-EM facility at UT will let Taylor continue to research CRISPR structures. He plans to study another recently discovered but poorly understood type of CRISPR Cas system.

“It’s still mysterious, no one knows how it works, so we’ll figure out how it works and how it functions using cryo-EM,” Taylor said. “There’s lots of different flavors of [CRISPR Cas systems], and my goal is to solve as many different structures as I can and understand how they work and how they are related to each other.”

The new microscope facility and the hiring of Taylor are part of a long-term plan for the molecular biosciences department to bring cryo-EM capabilities to UT, Leahy said.

“This is a revolutionary moment, and we have to have this technique,” Leahy said. “If we were to be a serious research institution, then our scientists would be left behind and they would not be able to study their systems at the same level of detail as scientists elsewhere without having access to this capability.”

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