Scientists See the Details with High-Resolution Crystals

Multi-chamber crystallization plate with porous plastic inserts placed in the precipitant reservoirs to reduce wicking. (Credit: Kristofer Gonzalez-DeWhitt)
Multi-chamber crystallization plate with porous plastic inserts placed in the precipitant reservoirs to reduce wicking. (Credit: Kristofer Gonzalez-DeWhitt)

HOUSTON (NASA PR) — Protein crystals tend to grow larger and more perfectly in space than on Earth, where gravity and other forces interfere. For scientists studying protein crystal structures, the difference is like watching high-definition television on a large screen versus standard-definition on a tiny screen.

“If you’re watching a hockey game on a small screen at low resolution, you can see the players and hockey sticks and maybe, just maybe, the puck moving around,” said Kristofer Gonzalez-DeWhitt, a scientist at Eli Lilly and Company. “But in high resolution on a large screen, you can see sweat on a player’s face.”

In other words, large, high-quality crystals allow scientists to see details in the physical arrangement of the molecules. This detail at near-atomic resolution could contribute to better medicine design back on Earth.

Gonzalez-DeWhitt is principal investigator for CASIS PCG 4-1, an experiment currently aboard the International Space Station. Using the microgravity environment of space, it aims to form crystals of proteins involved in the development of disease together with various investigational medicines. Back on Earth, scientists will X-ray the crystals to learn more about interactions between each potential medicine and protein.

A related investigation, PCG 4-2, crystallizes a human membrane protein involved in several types of cancer together with a compound that could serve as a drug to treat those cancers. In microgravity, these crystals will form without defects and irregularities that are typical of those on Earth and that make it harder to examine their structures.

The team from Eli Lilly and Company and CASIS, Kevin Tyre, Kristofer Gonzalez-DeWhitt, April Spinale and Michael Hickey, at launch site of their investigation. (Credits: Eli Lilly and Company)
The team from Eli Lilly and Company and CASIS, Kevin Tyre, Kristofer Gonzalez-DeWhitt, April Spinale and Michael Hickey, at launch site of their investigation. (Credits: Eli Lilly and Company)

Both investigations advance an approach called structure-based drug design. It uses information on the detailed structure of proteins and investigational medicines to guide design of more specific, effective and potent drugs.

“Structure-based design is a particularly powerful and insightful approach when detailed structural information is available,” said Gonzalez-DeWhitt.

For scientists, higher quality space-grown protein crystals may translate to higher-resolution structures, which they can use for insight into the spatial relationship between protein and medicine. Growing crystals with different compounds in reduced gravity also helps identify those selective to an intended protein target, much like creating a key that can open only one specific lock. This may lead to more effective medicines with fewer side effects.

Mission patch and the PCG investigation hardware. (Credit: Kristofer Gonzalez-DeWhitt)
Mission patch and the PCG investigation hardware. (Credit: Kristofer Gonzalez-DeWhitt)

It also accelerates the process of drug development, according to Michael Hickey, principal investigator for PCG 4-2 and a research scientist at Lilly.

“The beauty of all this is that by growing crystals in microgravity, we may be able to get to a potential medicine sooner,” said Hickey.

Gonzalez-DeWhitt and Hickey also are examining crystallization in various types of hardware. One is a commercially available plate that can accommodate a large number of samples in a relatively compact size, which maximizes use of available room on the space station. This plate is on its first trip into orbit and may become a viable alternative for future investigations on crystal growth in space.

The Center for the Advancement of Science in Space (CASIS), which manages the International Space Station U.S. National Laboratory, worked with the researchers to determine priorities for their investigations and translate those to the space environment.

“With these investigations, the idea is to take advantage of what has previously been demonstrated in terms of protein crystallography in microgravity,” says Michael S. Roberts, who holds a doctorate in microbiology and is deputy chief scientist at CASIS. “The microgravity environment will enable much better structure and better physical data.”

Everyone, it seems, appreciates high-definition images.