MSU NEWS SERVICE
BOZEMAN — Blake Wiedenheft didn’t set out to be involved in the development of a gene-editing tool that could eliminate numerous diseases.
Instead, he was simply following a passion that started with studying the microbes found in the extreme environments of Yellowstone National Park’s hot springs.
“I set out in one direction, and the road turned,” said Wiedenheft, associate professor in MSU’s Department of Microbiology and Immunology in the College of Letters and Science and College of Agriculture.
Now an internationally recognized expert on Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), a bacterial immune system that has been repurposed into a molecular scalpel for editing DNA, Wiedenheft tells the tale to illustrate the power of scientific inquiry that isn’t intentionally geared toward application.
“The scientific community didn’t discover CRISPR’s by looking for ways to edit genomes,” he said. “CRISPR’s were discovered by scientists who were trying to understand what happens when bacteria get sick.”
In the last installment of the 2018-2019 MSU Provost’s Distinguished Lecturer Series on April 9, Wiedenheft will share his personal story and explain how basic research on CRISPR’s has led to the transformative new technology. The free, public talk begins at 7 p.m. in the Hager Auditorium at the Museum of the Rockies and will be followed by a reception at 8 p.m.
Wiedenheft got his first taste of research as an MSU undergraduate, studying plant viruses in the lab of Mark Young, a professor in the Department of Plant Sciences and Plant Pathology. After earning his bachelor’s degree in 1998, wanderlust led him to work on a crabbing vessel in the Bering Sea, teach at a school in West Africa and work as ski patrol at Big Sky Ski Resort before he chose science as a professional path.
In 2002 he was back in Young’s lab as a doctoral student, studying viruses and bacteria that have evolved to thrive in Yellowstone’s thermal features. By day the researchers ventured into Yellowstone’s backcountry in search of yet-undiscovered microbes; by night, the exploration happened through a microscope. According to Wiedenheft, “Young’s enthusiasm is captivating, and his approach to science is unlike anything I had ever seen. He was embarking on an adventure and was willing to bring us all along.”
Expertise with viruses launched Wiedenheft into a postdoctoral research position at the University of California, Berkeley, in the lab of Jennifer Doudna, now a well-known name in the CRISPR world. The year he left for the position, researchers discovered that when the bacteria in yogurt were infected with a virus, they acquired snippets of the viral DNA and developed resistance to further infections.
“How any of that worked was not understood,” Wiedenheft said.
CRISPR is an acronym describing how bacteria essentially vaccinate themselves against viruses by incorporating fragments of viral DNA into their own genome, according to Wiedenheft. This sophisticated, adaptive immune system produces proteins that, like molecular scissors, recognize and snip the DNA of invading viruses to render them harmless.
By the time Wiedenheft returned to MSU in 2012, Doudna and her collaborators had found a way to tweak one of those proteins, called Cas9, so that it could be programmed to recognize and cut other specific DNA sequences, not just those of viruses.
Since then, the technology has been used to produce mushrooms that resist bruising and sheep that have longer wool, among other breakthroughs. While technical challenges remain, it’s reasonable to anticipate that CRISPR will have wide-reaching applications in human medicine and agriculture.
“In the future, I think most, if not all, genetic diseases will be curable with CRISPR,” Wiedenheft said. CRISPR will enable doctors to not just treat conditions like sickle cell anemia but to cure them, he said.
While much of Wiedenheft’s research involves fundamental science about how viruses subvert the bacterial CRISPR defense, he is also advancing CRISPR’s medical applications. Last year, his lab received $440,000 from California-based biopharmaceutical company Amgen to help refine the gene-editing tool. The funding was coordinated by the MSU Technology Transfer Office and the MSU Office of Research Compliance, and MSU will own the technologies developed by Wiedenheft’s lab.
As with any major technological breakthrough, there are risks, Wiedenheft said. He wants to help inform people about CRISPR so they can weigh the risks and the benefits based on accurate information.
And at root, he said, he is still a scientist fascinated with the complex microbial world that most people never see. “I was, and still am, fascinated by the outcomes of molecular warfare.”