Nature publication

Weston McDonald (Left), Nick Keul (Center) and Zachary Wood holding Nature, the magazine where there research was published. 

When Nicholas Keul, a graduate student studying biochemistry, and Zachary Wood, a professor of biochemistry at the University of Georgia, learned their research paper was to be published in Nature, one of the top academic journals in the world, they couldn’t contain their excitement.

“[Wood] called me, and I woke up at, I think it was 2 a.m. with seven or eight missed calls,” Keul said. “We knew we were going to hear [about the acceptance] late in the night.”

Wood had been corresponding with Nature and would be the first to hear the news from the London-based organization.

“I tell my family about it,” Keul said. “You say, like, the discovery of DNA, Watson and Crick that was published in Nature journal. That just gives a perspective.”

The process from experimenting to publishing was a long one.

“It was about a four-year project,” Keul said. “There were a lot of road blocks along the way … We were kind of stuck, and then we’d refine our hypothesis … I’ve seen the sunsets from [the Davison Life Sciences Complex] many times.”

Receiving peer reviews was a large part of the process, involving feedback from professionals in the field.

“We went through three rounds of peer reviews, which about took a year,” Keul said. “Because you’re getting the best critics in the world basically who are looking at your paper and critiquing the data and asking more questions, so we had to address all those questions.”

After these revisions, along with additional experiments, there was a long period of waiting. Their research was officially accepted on Sept. 10.

Keul and Wood, along with eight other UGA students, conducted experiments about the function of unfolded parts of proteins called intrinsically disordered segments. For more than 50 years, the central dogma of biology has been that the folded structure of proteins is important for function. The small unfolded portions were considered “junk segments” left over from evolution, and in some cases, they are actually removed when proteins are being studied.

Keul’s paper, titled The entropic force generated by intrinsically disordered segments tunes protein function,” shows that these intrinsically disordered segments are actually important.

These unfolded bits of protein make use of entropy, the energy that arises from the Universe’s natural tendency toward disorder.

“They act kind of like sails on a boat,” Wood said, comparing the force of wind on a sail. “Instead of catching wind, these disordered bits harness entropy to subtly change the structure of the protein, which gives it a new function.”  

Keul explained that similar disordered segments are found about 40 percent of proteins in the human body, which suggests that nature has been using this entropic force mechanism in the evolution of proteins.

This finding is important because it identifies a new way that proteins can evolve. It also changes how scientists study proteins. These disordered segments can no longer be dismissed as junk.

“To give an analogy, in the 90s, there was this idea that rDNA was full of a bunch of junk DNA. Like, we had genes, but there was a whole bunch of DNA … that weren’t assigned to genes, and now we know that it’s definitely not junk,” Wood said.

The process of using enzymes to produce chemicals has been slow or inefficient using modern chemistry techniques. Using this group-effort discovery, it might be possible to engineer better proteins for industrial or medical applications.

“We can now leverage our discovery to make these enzymes faster and more efficient,” Keul said.

Research on this is expected to continue in the future, with various other proteins being used against the original hypothesis.

“In biotechnology, we like to make proteins and use them to do chemistry in bioreactors,” Wood said. “People in industry want to make better enzymes and there are very intensive computational programs to try and do that with a lot of trial and error. This is a new tool that they can use.”

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