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Big-Time Byline

By Mick Kulikowski

For many scientists, it’s a pinnacle achievement: seeing your name listed as a co-author in Nature, the highest of high-octane scientific journals.

But for NC State graduate student Benjamin Wheeler, publishing in Nature is a study in serendipity.

A Ph.D. student in bioinformatics, Wheeler joins more than 70 co-authors from 20 academic or research organizations on the Nature paper, “The Dynamic Genome of Hydra,” published March 14.

And while the paper lifts the veil from a tiny sea creature that serves as a model organism for studying stem cell biology, it also stands as a powerful example of how a chance meeting got Wheeler involved in the project in the first place.

Ben Wheeler with Nature cover
A series of fortunate events led Ben Wheeler to a master's project that landed him in Nature, an achievement that is often decades in the making for scientists.

Collaboration and Coincidence

The path to Nature began off campus, when Dartmouth College biologist Dr. Kevin J. Peterson met Dr. Brian Wiegmann, an NC State entomologist, at an academic workshop on patterns in evolutionary history.

"Kevin and I found common ground through our interest in searching for new information from genome projects to support hypotheses about long-term evolution of animals,” Wiegmann says.

Peterson, who studies microRNAs – RNA snippets that regulate some cellular processes – and the ways they’ve evolved in animals, and Wiegmann, who is crafting the evolutionary “tree of life” for flies, decided to collaborate.

Peterson needed help in his investigation of animal evolution. Wiegmann consulted his computer science colleagues and found Dr. Steffen Heber, who works on statistical genetics and computational biology – studies that compare sets of genes, which requires making sense of large data sets. Heber, in turn, suggested Wheeler, one of his new graduate students in computer science.

So Wheeler set out to create a computer program that could help Peterson find microRNAs in animals whose genomes had not been sequenced. One of these was Hydra. The project became the focus of Wheeler’s master’s thesis and would eventually land him in the granddaddy of science journals.

Mining for MicroRNAs

Studying microRNAs is a good way to learn more about evolution because the snippets are passed on by ancestors without much change. However, microRNAs are added as an organism evolves, so new snippets are apparent when organisms branch out on their family trees.

Wheeler’s computer program, called miRMiner, examined RNA sequences to find new microRNAs.

“We couldn’t have done our microRNA work without it,” Peterson says. “Ben was very easy to work with – the major difficulties were in trying to conceptualize what the data would look like before we had it.”

“I didn’t think anything of it at the time; it was just one more set of data to run through the program,” Wheeler says about his work on the Hydra microRNAs. “I e-mailed the information back to Dr. Peterson, and, two years later, there’s something in Nature.”

School Serendipity

The serendipitous nature of research and collaboration – knowing a person who works with a person who may be able to help – is clear in Wheeler’s role in the Nature paper. But it also took a bit of serendipity to deliver Wheeler to Raleigh and NC State in 2006.

A high achieving computer science and math student at Thiel College in Pennsylvania, Wheeler initially applied to four graduate schools. When he didn’t receive an acceptance letter, Wheeler sent out another round of three applications, including one to NC State.

Ben Wheeler in office
Ben Wheeler has moved on to doctoral research at the Bioinformatics Research Center on Centennial Campus. He's studying alternative splicing, linked to human disease.

“NC State admitted me and gave me funding,” he recalls. “But I needed to give NC State a quick decision on accepting the offer. I hadn’t heard from the other schools yet, so it was a somewhat easy decision. ‘Here’s a bird in the hand, so I’ll come to State.’”

The proximity to Pennsylvania was important to Wheeler and his wife, Katie, too. As an added bonus, she quickly found a job in D.H. Hill Library on campus.

Good thing for NC State. It turns out that Wheeler eventually was accepted to and received funding from his other two choices. Score another victory for being in the right place at the right time.

From Sea Creature to Splicing

For his doctorate, Wheeler’s work in the Bioinformatics Research Center on NC State’s Centennial Campus has turned his focus to what is known as alternative splicing.

In cells, genetic information is used to make proteins, which direct the chemical reactions of cells. During this complex process, strands of RNA are spliced.

Wheeler and Heber are studying whether alternative splicing, in which RNA is spliced in more than one way to form multiple proteins, plays a functional role in a cell or if it is a processing error.

In humans, alternative splicing has been linked to disease – errors in splicing lead to errors in protein production, which  has harmful effects on people, the hypothesis goes – but research is just beginning to scratch the surface of this problem.

This time, Wheeler is working on the lab rat of the plant world, Arabadopsis thaliana, or mustard weed, which has high rates of alternative splicing. He’s trying to gauge whether alternative splicing serves as an off switch for functions in the plant or is just a random mistake.

Wheeler anticipates receiving his doctorate in bioinformatics in two years and says he’d like to perform research at a university or laboratory.

That’s time enough for Wheeler to make even more contributions to science as an NC State student, serendipitous or not.