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Mitch 翱鈥机辞苍苍别濒濒: A serendipitous path to CRISPR

Mitch O鈥機onnell joined the Center for RNA Biology at the 人妻少妇专区 Medical Center in 2017. (人妻少妇专区 photo / Matt Wittmeyer)

The Aussie native originally thought of becoming an astrophysicist. Now, he鈥檚 exploring the intricate universe of protein structures.

CRISPR regularly graces health and medicine headlines, with no sign of stopping. Within the sprawling field, 人妻少妇专区 professor and researcher is creating a niche by zeroing in on CRISPR-Cas13. His goal? To better understand prokaryotic antiviral immunity and RNA-mediated gene regulation, and to inform the development of RNA detection tools that could improve clinical diagnostics. The assistant professor of biochemistry and biophysics recently published two in Nucleic Acids Research, and聽in a found that this same Cas13 protein partners with a unique membrane protein to stop viral infection.

O鈥機onnell joined the University鈥檚 in 2017. Get to know him better as he shares his professional and personal path to Rochester.

WHAT鈥橲 UNEXPECTED ABOUT YOUR TWO NEWEST PAPERS?

翱鈥机辞苍苍别濒濒: We went in trying to understand allostery鈥攈ow something that happens at one site in a protein (say, a drug binding) affects what happens at a different, distant site in the same protein. We identified a central communications hub and discovered that single amino acid substitutions (in what is a huge protein) altered the transmission of information across the protein. We were shocked that such a simple change made a difference and were able to use this strategy to create new variants of Cas13 that are more sequence-specific with respect to RNA recognition, and show these can improve our ability to discriminate between closely related SARS-CoV-2 strains using a CRISPR-based diagnostic test.

Mitch O'Connell poses with the members of his lab need a helix-shaped sculpture.
Harnessing a range of interdisciplinary approaches, the members of the are working to understanding the biochemical mechanisms of RNA-mediated gene regulation. (Photo provided)

How鈥檇 you get into the CRISPR field?

翱鈥机辞苍苍别濒濒: I鈥檓 originally from Australia and got my PhD in Sydney, but wanted to do a postdoc in the US. I contacted a bunch of people, including Jennifer Doudna, to get interviews. I didn鈥檛 hear back, so I emailed Jennifer again and she asked me to visit her at Berkeley. This was back in 2012, and a week after our correspondence she published the Science study on CRISPR-Cas9 that won her the 2020 . I guess it was serendipitous that she replied to my email and I was able to join her lab; it was a really inspiring and invigorating time to be there.

Mitch O'Connell with his partner pose with their two-year-old, who is sporting ice hockey gear.
BRING YOUR A GAME: O鈥機onnell鈥檚 young son is a big fan of ice hockey, so don’t be surprised if you see the family at an area skating rink. (photo provided)

Outside of your own, what areas of research do you find most interesting?

翱鈥机辞苍苍别濒濒:聽Many things! I loved learning about astrophysics and the universe as a kid and went to college with the hopes of becoming an astrophysicist. However, in my first year, I fell in love with protein structure and function and quickly decided that鈥檚 the path I wanted to take.

In terms of recent research, I鈥檝e been fascinated with how we have greater than 1,000 different odorant receptor genes in our genome but each of our approximately 10 million olfactory neurons decides to randomly select and express just one gene from this gene family. How this regulation is thought to occur is fascinating and still a bit of a mystery, although scientists have made some .

What鈥檚 your favorite thing about Rochester?

翱鈥机辞苍苍别濒濒: How easy it is to live and work here, thanks to the quick commute and affordable housing. In terms of the University, I think our collaborative nature, collegiality, and support from the institution stand out as our biggest strengths. As do all of our undergraduate and graduate students鈥攖hey are excellent.

When you aren鈥檛 in your office or lab, where can we find you?

翱鈥机辞苍苍别濒濒:聽My two-and-a-half year old is obsessed with ice hockey, so I鈥檓 usually taking him to skating lessons. I鈥檓 also a big music head; I love seeing local bands in the area, or traveling to shows in Buffalo or Syracuse. I have a pretty extensive record collection, so I spend time buying and selling. I like most kinds of music, but have a particular penchant for anything that is dark, mysterious, and noisy.


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