Montana State University

Spring 2017

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Mountains and Minds

Insatiable curiosity June 06, 2017 by Emily Stifler Wolfe • Published 06/06/17

Blake Wiedenheft was working as a ski patroller and guide in Big Sky when he chose science.

Originally from Fort Peck, a tiny town in northeastern Montana, Wiedenheft, now 42, earned his bachelor’s degree in biology from Montana State University in 1998. He worked as a fisheries biologist on a crabbing vessel in the Bering Sea and spent a summer teaching school in West Africa. He said he was hooked on adventure, motivated by an insatiable urge to climb the next peak or see around the next bend. But, a chance encounter with Mark Young, a professor at MSU, completely reoriented his compass for adventure.

“Mark Young is a scientific pioneer and at the time he was chasing viruses that thrive in the boiling acid environments of Yellowstone National Park,” Wiedenheft said. “Before meeting Mark, I had never really considered how microbes would live in such extreme habitats, let alone think about viruses that infect these microbes. Mark’s excitement for understanding how these biological machines work was, literally, infectious.”

Now an assistant professor in the MSU Department of Microbiology and Immunology, which is part of both the College of Agriculture and the College of Letters and Science, Wiedenheft runs a research program focused on CRISPR, which stands for “Clustered Regularly Interspaced Short Palindromic Repeats.” These repeated DNA sequences are part of a sophisticated adaptive immune system that bacteria use to fight off viruses by slicing the viral DNA.

Wiedenheft explains the CRISPR process like this: Viruses are the most abundant and diverse biological agents on the planet, and most viruses infect bacteria. But bacteria are not defenseless. During an infection, bacteria steal short pieces of the viral DNA and record this DNA in the CRISPR in their own genome. Upon a subsequent infection, the bacteria uses genetic information stored in the CRISPR as a molecular record of previous infections.

“This memory is used to create molecular guides that direct cleavage of the viral DNA,” Wiedenheft said.

In the beginning, Wiedenheft’s work in the area was motivated by a desire to understand “what happens when bacteria get sick (i.e. infected by a virus),” but understanding how these immune systems work has led to a transformative new technology, he said.

“By studying how these systems work in bacteria, we learned that they function like programmable molecular scissors,” he said. “The bacteria use these systems to cleave viral DNA, but scientists are now ‘borrowing’ the CRISPR system from bacteria and reprogramming these systems to cut plant, animal and human DNA with precision.”

Among the many possibilities, CRISPR technologies are being used to try to cure diseases such as cystic fibrosis, sickle cell anemia, HIV and cancers.

“But with any transformative new technology comes an awesome responsibility,” cautions Wiedenheft, who has published 40 papers on the topic and speaks on the subject at universities and biotech companies worldwide.

“(CRISPR) has the potential to cure genetic diseases by correcting broken pieces of DNA, but this same technology can also be used to selectively eliminate certain species from the face of the earth.”

Wiedenheft’s contributions in the CRISPR arena are so significant that in January, President Barack Obama awarded Wiedenheft a Presidential Early Career Award for Scientists and Engineers, the highest governmental honor for early-career independent researchers.

Wiedenheft has been researching CRISPR since 2007 when he teamed-up with Professor Jennifer Doudna at University of California, Berkeley. At the time, Doudna’s lab was focused on the role of ribonucleic acid, or RNA, pathways in humans, and Wiedenheft’s background in viruses made him a good fit for the new project.

“He’s tenacious and fearless,” Doudna said of Wiedenheft. “He was willing to tackle a really big project when not a lot of others would. At the time, we knew CRISPR systems existed, but we had very little understanding of what they did, much less their potential applications.”

Gradually, Doudna’s lab shifted to focus primarily on CRISPR, and in 2012, Doudna and French scientist Emmanuelle Charpentier were the first to show CRISPR’s potential as a genomic editing tool. Doudna is now a Nobel Prize contender, thanks in part to foundations Wiedenheft laid while he trained in her laboratory.

Ross Wilson, a scientist in the Doudna Lab at Berkeley, remembers Wiedenheft’s intense passion and drive. There was one weekend, Wilson recalled, when Wiedenheft spent a straight 48 hours doing an experiment. He literally slept next to it.

That work ethic, Wilson said, was also coupled with a play-hard sensibility. After lunchtime road bike rides, Wiedenheft would start doing science immediately, still wearing his cycling gear. Sometimes he’d walk around the lab for hours in his helmet.

As a leader in one of the hottest fields in life sciences today, Wiedenheft could likely work anywhere he wanted. But he has chosen MSU, drawn home by deep roots and a connection to Montana.

The son of a fisheries biologist and a soil scientist, Wiedenheft grew up spending time on Fort Peck Reservoir, working on friends’ ranches, doing 4-H, running track, playing football and wrestling. As an undergrad and graduate student, he skied and ran the trails near Bozeman.

“At a time when technology allows such facile communication between scientists in different locations and from different disciplines, there’s no reason you can’t do cutting-edge work at a small land-grant institution, and the students at MSU are second to none,” Wiedenheft said.

Yet, Wiedenheft is a researcher who loves teaching and is a mentor to his students, as Young once was to him.

Josh Carter, who as a freshman heard Wiedenheft speak, immediately signed on to work in his lab, because “Blake’s passion was infectious.” Carter graduated this May with degrees in mechanical engineering and microbiology, and the research he performed in Wiedenheft’s lab helped him win a 2017 Rhodes Scholarship, as well as a Goldwater Scholarship.

“He gives 120 percent to everything, and he pushes you to give 120 percent, as well,” Carter said. “He genuinely wanted to help me be a better student and researcher, and a better all-around person.” ■