Senior Natalie Meckel per­formed research in a lab at Uni­versity of Nebraska-Lincoln this summer. Natalie Meckel | Courtesy

Over the summer, senior Natalie Meckel was admitted to a research program, spending the summer crys­tal­lizing pro­teins for neutron dif­fraction exper­i­ments at the Uni­versity of Nebraska-Lincoln to take part in the 10-week Redox Biology Center Summer Research (REU) Program.

“I’d planned on doing research ever since I was a freshman as part of my bio­chem­istry major,” Meckel said. “There were a ton of pos­si­bil­ities in the Redox Biology Center.”

Her research focused on struc­tural biology regarding human DJ‑1, a protein that plays a sig­nif­icant role in Parkinson’s Disease. Meckel explained that “familial Parkinson’s disease is caused by muta­tions in the human genome, a col­lection of which desta­bilize human DJ‑1 and impair its function.”

According to Meckel, this is what makes human DJ‑1 of interest in factors leading to the neu­rode­gen­er­ative disease. Although it is known what causes this in familial Parkinson’s disease, it is unknown what the cause is of spo­radic Parkinson’s disease.

“In order for us to under­stand exactly how DJ‑1 plays a role in spo­radic Parkinson’s Disease, we need to under­stand what other factors might lead it to be deac­ti­vated besides mutation,” Meckel said.

She said under­standing the “struc­tural nuances of DJ‑1 will help us determine what envi­ron­mental factors cause it to be desta­bi­lized,” and that is why the hydrogen bonds in the protein are key com­po­nents to study. Meckel’s research con­cen­trated on devel­oping a crys­tal­lization pro­cedure for the protein. If the crystals are large enough, they can be used for neutron dif­fraction exper­i­ments to locate the hydrogen bonds. These exper­i­ments are only pos­sible with a nuclear reactor.

“You actually shoot neu­trons at it, and the neu­trons bounce off of mol­e­cules based on their nuclei,” Meckel said. “Hydrogens are really sen­sitive to this type of exper­iment.”

In the exper­iment, it is important to localize hydrogen bonds because “current models predict several key hydrogen bonds” sur­rounding an amino acid called Cys­teine 106, she explained. Cys­teine 106 is critical to DJ‑1’s activity, and “factors that might affect its reac­tivity, such as nearby hydrogen bonds, likely have a role in the cause of Parkinson’s.”

“That’s why the whole goal of my pro­cedure was making crystals that would enable us to localize hydrogen bonds,” Meckel said. “If we were able to totally under­stand what causes DJ‑1 to be dis­abled or inac­ti­vated in people with Parkinson’s, we could work on con­structing a phar­ma­ceu­tical that would pos­sibly prevent that from hap­pening.”

Meckel’s crys­tal­lization pro­cedure that would allow researchers to perform the exper­iment and locate the hydrogen bonds was simple but del­icate. She expressed the protein in E. coli bac­teria and purified the protein for crys­tal­lization exper­i­ments.

After the protein was con­cen­trated, she placed a tiny drop of oil in a well of a plastic tray, and on the bed of the oil, she put tiny drops of poly­eth­ylene glycol, a solution known to cause a protein to pre­cip­itate into a solid. Using a cat whisker, she put miniscule amounts of crushed up protein crystal on each drop.

“By varying the type of oil and the con­cen­tra­tions of protein, poly­eth­ylene glycol, and crushed crystals called microseeds, I opti­mized the pro­cedure to produce large tetragonal crystals,” Meckel said.

Dean of the Natural Sci­ences Christopher VanOrman, Meckel’s junior research adviser who reviewed her junior thesis on the role of DJ‑1 in Parkinson’s, said Meckel had been inter­ested in the DJ‑1 protein the year before, and she was well pre­pared to do this type of bio­chem­istry research.

“Natalie excels in critical thinking, quan­ti­tative rea­soning, sci­en­tific inquiry, and her written com­mu­ni­cation,” VanOrman said. “She is one of our best and brightest stu­dents.”

Assistant Pro­fessor of Chem­istry and Meckel’s aca­demic adviser Courtney Meyet agreed, saying that Natalie has been a teaching assistant for her this year and last year.

“Natalie is approachable and has a pos­itive attitude,” Meyet said. “It is no doubt these attributes served her well during research.”