Researchers at UW-Madison are leveraging a unique quirk of animal biology to improve an imaging technique used to identify targets for drug therapies.
A team led by Prof. Ci Ji Lim recently published a study in the journal Nature Communications detailing this research, which is focused on boosting the clarity of images captured through cryogenic electron microscopy, or cryo-EM.
This imaging technique involves freezing samples in a thin, water-based film and taking images of them with an electron microscope, which enables high-resolution pictures of microscopic structures such as proteins and other cellular structures. One challenge with this approach is that damage to the structures being studied is more common at the edges of the sample, reducing the quality of the image.
“When proteins interact with this interface, they can clump together along the edges or begin to unfold and irreversibly change their form,” Lim said in a statement. “There are many proteins that we just haven’t been able to fully explore the structures of because of this problem.”
To address this issue, the team of scientists looked to an organism called a tardigrade, or water bear. They’re well-known for being among the most resilient creatures in nature, having the ability to withstand some of the most punishing conditions imaginable. That includes extreme temperatures, very high and low pressures, radiation, dehydration and even exposure to the vacuum of outer space.
This ability is thanks to specialized molecules they produce called “late embryogenesis abundant” proteins, or LEA. These proteins “keep the animals’ essential cellular structures and proteins intact” while they dry up and go dormant, making it possible for them to rehydrate and revive when conditions improve, according to the university.
After adding the LEA proteins to microscope samples before cryo-EM imaging, the research team determined this approach results in clearer images without much added effort or expense. The release notes it can also be used alongside other sample protection measures.
“Adding LEA proteins is a readily deployable and cost-effective solution to a bottleneck in cryo-EM research,” Lim said in the release. “It is exciting that we got here using proteins that naturally evolved to do a similar job … There’s the potential for us to learn so much more about the structural biology of many proteins that had been challenging to visualize.”
Lim has filed a provisional patent with the Wisconsin Alumni Research Foundation covering the research.
