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Brian Lehrer: Brian Lehrer on WNYC, and there are geniuses among us. The 2020 MacArthur Fellows were named a couple of weeks ago. That's the official designation of this group of "exceptionally creative individuals", but they are better known as MacArthur genius grants. Our listening area turns out to be home to quite a few of them this year. All week, on the Brian Lehrer show, we have lined up a genius-a-day to end the show with five duly minted genius prize winners, one each day at the end of the show this week, all week.

Today, we wrap it up with Princeton biological chemist Mohammad Seyedsayamdost who was honored to "what the MacArthur foundation had to say for investigating synthesis of novel molecules with therapeutic properties and expediting discovery of new antibiotics." Congratulations. Welcome back, and thank you for joining us today and sharing your genius, doctor.

Mohammad Seyedsayamdost: Thank you very much, Brian. Thanks for having me.

Brian: As I said, the MacArthur grant is for exceptional creativity, and all this week, we've been hearing from artists like writers and filmmakers and singers. I'm glad they also recognize the creativity of scientists, especially now that we're counting on scientists more than ever, but were you surprised therefore to get this?

Mohammad: I think one is always surprised. This is one of the awards where you don't know you're being nominated, you don't know you're being considered, and the first time you signed out is when they make the phone call to tell you you won. Absolutely, I was very, very pleasantly surprised.

Brian: Your work I see is with fighting bacterial infections, not viruses. While you aren't on the front lines of SARS COVID-2 research, the threat from antibiotic-resistant bacteria is not a small problem by any means, and that's what you've made advances in. Can you explain a little bit about your work to our lay audience?

Mohammad: Yes, absolutely. It turns out bacterial infections, infectious disease in general, is obviously one of the major health threats of the 21st century. It turns out that what we have used to fight the bacterial infections are molecules that come from bacteria, innocuous, soil-dwelling bacteria that we use to extract molecules from, and then fight those infections that occur inside our bodies. What we learned around 15 years ago, and I say, we as a community, is that these antibiotics, these low-hanging antibiotics had already been picked.

We learned that there is probably another 5 or 10 times as many antibiotics that these soil-dwelling bacteria can synthesize that conventional methods were not able to access and are not able to access. What we've been interested in and what we've developed is a method that allows us to access these otherwise difficult to reach or difficult to identify antibiotics, and then to examine their properties as potential therapeutic agents.

Brian: I see you've talked about this concept of how molecules talk. Explain for us how your invention of a method called HiTES works and how it's making a big difference in figuring out more about the language of molecules and how they communicate.

Mohammad: Bacteria essentially communicates with the language of small molecules with a chemical language. You can think of the molecules that they exchange among each other as words, and you can think of the function of those molecules as meanings. This really constitutes a chemical language with which bacteria interact and communicate and compete with their environment.

This gets a little deeper into our method, but what we realized is that we needed to coax bacteria into producing these antibiotics that they clearly could synthesize, but were not synthesizing under normal growth conditions. What we did was bombard them with different types of natural molecules and see which ones they reacted to by synthesizing their repertoire of antibiotics. It was essentially getting into a conversation, if you will, with the bacteria, and again, if you will, talking them into producing the antibiotics that they can.

Brian: I see aside from talkative molecules or in addition to them, you've also discovered fratricidal molecules. Oh, what does that mean at the molecular level?

Mohammad: It's something we're still trying to figure out. This was also surprising. It turns out aside from molecules that are meant to kill your competitor, bacteria also make molecules to kill their own kind. It really is a exercise that allows a bacterial population to remain fit. It essentially, so to say, sacrifices sibling cells, freeze up their genetic information, which has been used by the surviving population to make it more genetically diverse. That's what we think is going on, but it's really early days in the research.

Brian: What disease do you think your research is most likely to be productive at discovering something that can fight it?

Mohammad: Right now we're following up on some nice hits that we've seen or nice therapeutic molecules that we've isolated against Clostridium difficile or C. diff. That's one of the infections that occurs in the body when there's an imbalance in the gut microbiome.

Brian: Oh, good, because I know people who've had that and it's no fun. In fact, ironically, as you work on antibiotics, that can be a side effect of antibiotics in some cases.

Mohammad: That's exactly right. Our tools to fight C. diff infections are limited at the moment. That's one area that we are targeting. Another area, if I may add quickly, another area that we that we're targeting is drug resistant Neisseria, the causative agent of gonorrhea.

Brian: You've lived and studied around the world. I see Iran, Germany, Australia, in this country, in Boston, and now Princeton. Do you find science to be a kind of universal language, or do you find, even within science, which is purely objective as anything yet, different styles?

Mohammad: I do find science as a universal language. I think living in those countries, the significant benefit was growing up with and experiencing different cultures, but the scientific language was constant. It was always happening. It was always one way, even if you didn't know the language of the country, it was one way to communicate and exchange with other scientists, so that I have certainly appreciated.

Brian: Do you have a dream discovery when you're working in the lab you run at Princeton?

Mohammad: That's a very interesting question. I think the dream is always to find the truth, right? Find the truth in what you're doing. I think it's a little dangerous to have a dream discovery because then you're predisposing yourself to certain things and perhaps blocking out other things. When you're working in the lab, I think you're trying to be as open as possible and find what the experiment and what the system is trying to teach you, is trying to tell you, and be open to any surprises that you might find.

Just as an example, the fratricidal molecule is something we would have never dreamt of discovering, but it's certainly something we found because we were open to the idea that that is a function that we could identify.

Brian: We're going to leave it there. Thank you, Princeton biological chemist, Mo Seyedsayamdost. We thank all the new MacArthur genius grant winners for coming on, all five of them who came on this week. We're actually going to add one on Monday because that's how many they are, a lot of New York, New Jersey, Connecticut area geniuses, newly minted this week. Dr. Seyedsayamdost, thank you very much for being part of this series.

Mohammad: My pleasure. Thanks for having me, Brian.

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