Professor Blake Wiedenheft

By Petra Celadova

Professor Wiedenheft is an Associate Professor in the Department of Microbiology and Immunology at the Montana State University. His fruitful career has been marked by a profound interest in the mechanisms that viruses use to subvert the immune response of their hosts, and the incredible systems that microbes mount in their defense against viral pathogens. Dr. Wiedenheft’s focus is to understand the functionality of such cellular machines, with the aim of harnessing this knowledge to engineer molecular systems for practical applications. Among a number of other interesting projects, in response to the current global pandemic, Dr. Wiedenheft’s team is now developing CRISPR-based viral diagnostics for SARS-CoV-2. “We are still in the early stages of development,” Dr. Wiedenheft remarked, “but early indications suggest that this approach will be competitive.”

Dr. Wiedenheft’s career trajectory has been an adventurous one. Upon completing his undergraduate degree, he felt he “wasn’t yet ready for life at the bench”, and even “thought that science might have been a college fling”. In a deeply felt need for an adventure, he went touring in West Africa, crabbing in the Bering Sea and ski patrolling at Big Sky Resort in Montana. The time spent out in the world on adventures helped him to realize that science was not just a college fling after all, and that it might well be a true love. “The longer I was away, the more I yearned to be back in the lab,” Dr. Wiedenheft said. “What I finally realized is that science is an adventure, and I have not stopped trying to climb the next mountain or peek around the next corner.” In keeping with this perception, he offered the following tip to the young scientist: “My advice is to find your own adventure.” And we can safely say following this advice has certainly worked out well for Dr. Wiedenheft, as he concluded: “Eighteen years after starting my PhD, I’m still in love with science.”

After returning into academia for his doctorate at Montana State University, Dr. Wiedenheft’s curiosity about viruses, dating back to his pre-doctoral days, was well nourished by his PhD advisors, Profs. Mark Young and Trevor Douglas, who “fostered his curiosity and fueled his love for science”. Dr. Wiedenheft’s PhD project was a treat for his adventurous spirit, as his “job” was “to hike around Yellowstone National Park, collect samples from boiling acid hot springs and bring these samples back to the lab for cultivation” in search for viruses of thermoacidophilic Archaea. This project kindled Dr. Wiedenheft’s interest in the perennial arms race between viral parasites and their hosts, and paved the way to his postdoctoral position in Prof. Jennifer Doudna’s lab, at the University of California, Berkeley.

“What I finally realized is that science is an adventure, and I have not stopped trying to climb the next mountain or peek around the next corner.”

There awaited him another adventure, as he was the first person in the Doudna lab to work on CRISPRs. How was working on CRISPR while it was becoming a world-wide phenomenon? It was “simultaneously exciting and scary”, remembered Dr. Wiedenheft. “In the beginning, each new experiment nearly doubled what was already known, and it felt like we were riding a scientific catapult, launched each day into a new landscape of discovery. As the field grew and the landscape matured, the chances of a transformative new discovery decreased incrementally, but the competition grew steadily, and the culture of this community evolved accordingly,” he continued. Just as he was ready to set up his own group back at Montana State University, continuing in the CRISPR research, the 2012 publications showing that CRISPRs and Cas9 could be used for targeted genome engineering came out. It was “like dumping white gas on an already hot fire,” Dr. Wiedenheft reflected. “The field exploded, and I was concerned that all the attention, resources, and big labs at marquee universities were about to steam-roll my nascent research program that was just getting off the ground at a small state school in Montana. Coming from Jennifer’s lab, I knew the caliber of my competition (whip-smart and willing to work 24x7), and it scared the hell out of me,” he confessed. Luckily, however, “that fear, some good luck, and many incredibly talented scientists that chose to join my team have helped keep our work at the forefront,” Dr. Wiedenheft concluded.

Unsurprisingly, Dr. Wiedenheft mentioned that stress management has been a major challenge for him. In a piece of invaluable advice from Prof. Doudna, he was once told to ”focus on doing good science and the rest will work out”. Apart from that, he recognized that “making time to exercise in the mountains has always been good medicine. Nature is a great place to blow off some steam and stumble across inspiration,” he added. Apart from nature, Dr. Wiedenheft continues to be inspired by students and viruses. “Viruses, and students, frequently remind me to stay open-minded and to think of new ways to solve problems. Viruses are, above all else, problem solvers. The first problem is entry, then immune evasion, and so on. Viruses have demonstrated that you do not need to be big to be effective.”

Dr. Wiedenheft’s favorites in the RNA world are small RNAs, with CRISPR RNAs in particular. “If you pushed me to be a little more creative,” he added, “I would say modified RNAs. We recently teamed up with Kristin Koutmou’s lab at the University of Michigan to identify RNA modifications and determine the biological consequences of these modifications.” You can follow Dr. Wiedenheft’s lab on Twitter (@WiedenheftLab) or you can get in touch with him using the good old-fashioned email ([email protected]). Dr. Wiedenheft kindly encourages any interested scientists to reach out to him, as the lab is “always looking for scientists that feel more inspired under the shadows of mountains than under cover of skyscrapers.”