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In this episode of Brains, Black Holes, and Beyond, we sit with Dr. Cameron A. Myhrvold, an assistant professor in the Molecular Biology at Princeton whose research is concentrated on using CRISPR to develop new technologies to detect pathogens.
Brains, Black Holes, and Beyond (B Cubed) is a collaborative project between The Daily Princetonian and Princeton Insights. The show releases 3 episodes monthly: one longer episode as part of the Insights partnership, and two shorter episodes independently created by the 'Prince.' This show is produced by Senna Aldoubosh '25 under the 147th Board of the 'Prince.' Insights producers are Crystal Lee, Addie Minerva, and Thiago Tarraf Varella. This show is a reimagined version of the show formerly produced as Princeton Insights: The Highlights under the 145th Board of the 'Prince.'
Please direct pitches and questions to podcast@dailyprincetonian.com, and any corrections to corrections@dailyprincetonian.com.
Senna Aldoubosh 0:13
Hi everyone, welcome to Brains, Black Holes, and Beyond–a collaboration podcast between the Princeton Insight newsletter and the Daily Princetonian. From the prince, my name is Senna Aldoubosh. My name is Ketevan Shavdia. Today's guest on the show is Dr. Cameron A. Myhrvold, an assistant professor in the Molecular Biology department. Dr. Myhrvold got his bachelor's at Princeton in Molecular Biology before going to Harvard for his PhD in Systems Biology. He did his postdoc in Harvard and MIT before coming back to Princeton in January of 2021, where he now runs his own lab, which develops CRISPR based technologies for studying viral and host RNA, as well as detecting and destroying viral RNA. Dr. Myhrvold, thank you for joining us.
Ketevan Shavdia 0:59
So our first question is more of a general interest question. But how did you choose Molecular Biology specifically CRISPR related research as a field you wanted to pursue?
Dr. Cameron Myhrvold 1:06
That's a great question. So when I was a sophomore at Princeton, I was actually trying to figure out, you know, what to major in, as I'm sure many of you who are listening now are and initially, I came into Princeton thinking that I was more interested in Physics. But then I started taking classes in particular, I took the Integrated Science Curriculum here at Princeton, and it was, that really kind of taught me that there were so many more like new unanswered questions in biology, whereas a lot of the stuff in Physics I was learning, you know, was from like, the 19th century or the early 20th century. And so I just got a lot more excited by all these unsolved problems in biology. And so that's what kind of shifted in my mind. And then I realized, hey, that's really what I want to pursue, you know, going forward.Now, by the time I graduated Princeton, so in 2011, CRISPR, really wasn't that big of a thing. It wasn't until 2012, that there was the kind of major breakthroughs by Jennifer Doudna, and Emanuel Charpentier, that really kind of kick started the field. So, you know, in graduate school, I got really excited by Synthetic Biology, and kind of was pursuing that for a while. But then I saw what was happening, you know, in the CRISPR field, and kind of how revolutionary it was. And right, as I was wrapping up my PhD, there was a new CRISPR protein that was discovered, which at the time was called C2C2, it's now called Cas13, which was the first sort of RNA targeting CRISPR effector protein.
And so then I saw that, and I was like, wow, this is really exciting. There's a lot of potential here to use this as a tool to study RNA in lots of different settings. And so when I was looking at labs, you know, to do up to a postdoc, and I really got excited about the possibility of kind of working in that space and working with this newly discovered, you know, protein.
SA 2:41
That's awesome. So we had a question specifically about one of your papers. We saw one of your studies that discussed using something called like microfluidic combinatorial arrayed reactions for multiplexed evaluation of nucleic acid, which mCARMEN a lot easier to pronounce,
to diagnose up to 21 viruses, including COVID. Could you talk to us about what mCARMEN is and how you went about conducting this research?
CM 3:07
Yeah, definitely. So the mCARMEN story really starts a few years earlier, when we were developing the kind of original CARMEN technology. And the inspiration for that was basically that whenever you go to get tested, you know, at hospitals, they're typically testing for like one thing at a time. So you might get like a TB test, or a strep test, or a flu test or something like this. But there's really not a lot of testing for multiple things at a time. And we sort of felt like there was an important gap to be filled there, to enable things like disease surveillance, but also to test for unknown infections, where you don't really know what's making someone sick. And so you want to test a whole bunch of things at once. And so that's kind of what originally inspired us.
We sort of did that using this droplet based, you know, approach, which was the sort of original CARMEN technology. And that was really exciting. And we were able to demonstrate, you know, lots of detection of more than 100 different viruses at a time. But that technology had some key limitations, namely, that it relied a lot on kind of custom equipment. And the protocol was not very easy for people to use. And so we realized that that was gonna be a major bottleneck in terms of, you know, the technology, but we're getting used more widely.
And at the time, you know, the CARMEN paper came out in like May of 2020. At the time, we realized, Oh, my goodness, there's this huge need for something that is, you know, that can actually be scaled and used more widely, but that has similar principles as the original kind of karma technology. And so that's where the idea for mCARMEN really came along. We sort of figured, Hey, I wonder if we can use an existing, like microfluidic platform, which was made by a company called Fluidyne. They're not called standard bio tools, but it's basically the platform consists of these integrated fluidic circuits that allow you to take a series of inputs like different samples. And then, you know, in the case of mCARMEN, different CRISPR RNAs to kind of probe those samples for the presence or absence of different, you know, pathogens. And so that was very much in line with this original common vision, but it was using kind of the Fluidyne to help make that a possibility. And so, with mCARMEN, we were able to greatly simplify the protocol to something that could be conducted in a clinical lab, and also develop not only respiratory virus panel, but also panel detecting viral variants, that which became really important as Omicron, spread through Massachusetts, back in December of last year.
KS 5:40
So what are some future implications for your research? Do you think mCARMEN and some other technologies to develop or co-developed, like CARVER and SHINE could be used to treat COVID and other viral infections? Or are they intended as solid detectors of viral RNA?
CM 5:55
Yeah, that's a great question, I view them as two sides of the same coin. So we, as COVID showed us, we really do need to get better at doing testing and testing for lots of things. And so that's what, that's why we think that detection is such an important part of the problem, you need to kind of catch these pandemics before they spread to everybody.But I'm also really excited about CARVER, which is the more antiviral therapeutic technology that we developed, and actually recently started to commercialize. So I co founded a company last year that's trying to commercialize CARVER called Cargo Biosciences is the company. And the idea there is can we actually take that approach and really develop it into a drug that could be used against a variety of different, you know, RNA viruses that infect people, such as influenza, or SARSCOVID , or various other RNA viruses.
SA 6:47
So what are the next steps in your research? I know you kind of touched up on this with CARVER, but what are you currently working on? And what do you hope to accomplish?
CM 6:55
Yeah, that's a great question. So I think, you know, what about half of my lab does is really building on the work that I did as a postdoc. So continuing to push the forefront on the nucleic acid detection side of things, there's so many different applications there. And so many different pathogens, we want to be able to detect, you know, things like tuberculosis, or monkey pox, or influenza that we really hadn't dove into as much back when I was a postdoc. And then I'd say the other half of the lab is really investigating new areas, kind of developing new technologies. And those are very kind of early stage. So it's hard to say where those are going to go. But I'm really excited there. Because, you know, when I started the lab, I really felt and I still do strongly feel that Cas13 has this kind of broader potential than just detecting and destroying nucleic acids. I mean, that's what I focused on previously. But it's really a way to direct Cas13 to RNA and that could be any RNA inside of a cell outside of the cell, what have you. So there's a lot more applications that I think are just beginning to get explored.
KS 7:51
Our last question is more of a general ending question. But what is the most misunderstood thing in your field or misconception the general public may have about your field of study?
CM 8:02
Great question. Let's see. Yeah, I think probably the biggest misconception stems from, you know, a few years back when CRISPR babies were in the headlines and all of that.And so I think that there is this kind of misconception that CRISPR is all about, you know, gene editing, or genome editing. And while that's obviously a super important, you know, part of what CRISPR has done for biology, I think the technologies that have been able by by CRISPR, and that's both Cas9 and C13– all sorts of things go well beyond just making edits to DNA, or the RNA. There's been an explosion of technologies for enriching nucleic acid sequences for imaging and all sorts of other things. And I think that's kind of underappreciated by the general public, because the headlines are so focused around, you know, editing, and, you know, to the exclusion of all else, basically.
SA 8:58
Cool. Is there anything else you wanted to be included in this podcast? Maybe like, any advice for anyone listening or just like any other bit about CRISPR?
CM 9:09
Yeah, great question. I think, you know, one of the things that excites me about it so much, and I would encourage, you know, students who are thinking about research to, you know, kind of get involved. This is, you know, people often think that you have to come in with all of this expertise to be successful at research, and really, particularly in a field like, CRISPR, that's not totally the case. I mean, yes, you need to learn a lot, you need kind of that foundational knowledge, but it's also a pretty new field. And so, you know, people can often come in and make a really big, you know, impact. And that's particularly the case you know, for interdisciplinary work, which I'm a huge fan of, so we do a lot of that in the lab, and I encourage people with all sorts of different backgrounds to consider, you know, research.
SA 9:52
Oh, awesome. Dr. Myhrvold, thank you for joining us today. It was really awesome learning about your research and best of luck with all your work this
SA 10:00
This episode of B-Cubed was hosted by me and Ketevan Shavdia, sound engineered by Oyshee Lahiry and produced under the 146 Managing Board of the Prince. For more information about Dr. Mhyrvold’s research, visit the links in the podcast episodes description. From the Prince, my name is Senna Aldoubosh. Have a great rest of your day.
Transcribed by https://otter.ai