The University of Utah is one of just five institutions in the world to be awarded a $2.5 million grant to purchase a state of the art cryo-electron microscope (cryo-EM), the Beckman Foundation announced today. The microscope, which will be able to visualize the structure of proteins and DNA at an atom-by-atom scale, will be installed in the Crocker Science Center, currently under construction on Presidents Circle. The microscope’s resolution is fine enough to see details such as the double-helix and ladder structure of DNA, said biochemistry professor Wesley Sundquist.
“Biochemistry and molecular biology take place on the atomic scale, enzymes work on the atomic scale, drugs bind on the atomic scale – so that’s information that’s really critical for understanding how biological processes work,” Sundquist said.
Within the cells of our body are dynamic worlds that have remained largely enigmatic because they are so small. Though much of the cell’s machinery is only a few billionths of a meter in size, these machines are essential. For instance, proteins work together to literally build the fibers of our being, to defend us from foreign invaders that cause disease, and to shape our DNA blueprints throughout life.
But as they say, a picture is worth a thousand words. With the specialized microscope, scientists can see the miniscule machines with their own eyes, directly documenting what they look like and how they work.
Before cryo-EM microscopy, researchers hoping to discern the atomic structure of proteins, molecules, drugs or DNA relied on X-ray crystallography, a labor-intensive process that required growing crystals of pure samples of the protein or molecule.
In cryo-EM, samples are not stained, treated or enclosed, as they are in traditional microscopy or in X-ray crystallography. Instead, they are frozen instantly. Further, the sample does not need to be as pure as in X-ray crystallography. The microscope takes many two-dimensional images of a molecule or protein that are then computationally combined to create a three-dimensional image. The new instrument will be more powerful and precise than the U’s current cryo-EM unit, which is housed in the Aline Wilmot Skaggs Biology Building.
The new instrument is an FEI Titan Krios, and is scheduled to begin installation in November 2017, shortly after completion of the Crocker Science Center. Because the instrument must be assembled on site, installation will take two to three months.
The microscope’s extreme sensitivity dictated the design of the room it will eventually occupy. “We need the instrument to have stable electronics and operating temperature and to hold the specimen very still. The instrument’s components do these things very well,” said David Belnap, director of the Electron Microscopy Core Laboratory.
The temperature in the room will be held to daily fluctuations of no more than 0.8 degrees Celsius (1.4 degrees Fahrenheit), Belnap says. The ventilation system is designed to avoid blowing on the microscope, since air breezes could disturb it. Even talking in the room during microscope operation would produce undesirable air movement and vibration, so operators will control the microscope from a separate room.
Further, to isolate the instrument room from all other vibrations in the building, the microscope will sit on a specially-designed concrete subfloor pad.
The cryo-EM instrument will be the most precise microscope in Utah. Researchers from other universities have already expressed interest in scheduling time on the microscope. In comparison with peer institutions, Sundquist said, “it catches us up to the very best of the Pac-12 and other leading research institutions throughout the world.”
“Proteins form complexes in cells that perform the functions that are necessary for life,” Belnap said. “If we need energy, proteins catalyze chemical reactions. If we need DNA copied, proteins catalyze that. The new instrument will enable us to study these structures at a level of detail that has not previously been possible.”
Researchers from across campus came together to complete the grant application. Below are three examples from U researchers of the type of research that a cryo-EM microscope makes possible.