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Focus In Sound

Focus In Sound

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The Burroughs Welcome Fund FOCUS Newsletter Podcast Economics
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  • FOCUS In Sound #37: Jennifer Brophy
    Nov 6 2023
    FOCUS In Sound #37: Jennifer Brophy ERNIE: Welcome to FOCUS In Sound, the podcast series from the FOCUS newsletter published by the Burroughs Wellcome Fund. I’m your host, science writer Ernie Hood. In this edition of FOCUS In Sound, we welcome a young investigator who is pioneering in the field of plant tissue engineering—a remarkable emerging technology that just might eventually save the human race. Jennifer Brophy received one of the Burroughs Wellcome Fund’s Career Awards at the Scientific Interface, or CASI, in 2019. She is an Assistant Professor of Bioengineering at Stanford University, and is a Noyce Family Faculty Fellow and a Chan Zuckerburg Biohub Investigator. Jenn received her BS in bioengineering from the University of California, Berkeley in 2009 and her PhD in biological engineering from MIT in 2016. She did her postdoc work at Stanford, where she started looking at plants. Today in her lab, she and her colleagues are developing technologies that enable the genetic engineering of plants and their associated microbes with the goal of enabling innovation in agriculture for a sustainable future. Jenn Brophy, welcome to FOCUS In Sound! JENN: Thank you, I’m happy to be here! ERNIE: To get us started, Jenn, why don’t you give us a quick overview of your field, which is known as synthetic biology? JENN: Certainly. Synthetic biology can mean a lot of different things to different people. In my lab, we think of it as advanced genetic engineering, which is essentially applying the principles of engineering to biology in order to reprogram living cells or organisms to do something new. In our lab, that means changing the shapes of plants as they grow, but for different people they engineer organisms to do different things. ERNIE: I see. Building on what you just told us, I’d like to find out more about one of your major areas of research, which is called synthetic gene circuits. I know that it was the subject of one of your most important publications to date, which came out in Science last year. Please explain… JENN: In that work, using synthetic genetic circuits to control gene expression patterns in multi-cellular organisms. This work is really borne out of the observation that gene expression patterns are important for development. In the 1980s—I’m going to do a little historical bit—in the 1980s, scientists discovered a gene in Drosophila called antennapedia that controls the formation of legs, and stunningly, if you express that gene in cells on the head of a fly, you can actually get it to produce legs where it would usually have antenna. Now that’s shocking, but it’s also really highly conserved across organisms. Where you express genes in the body affects the way it develops. And so we were interested in trying to control where in an organism we’re expressing genes in order to change its development. But it raised this question of how do you control gene expression across the body of a multi-cellular organism? So what people usually do when they want to pick out specific cells within a body to express a gene in is they look for a promoter, a region of DNA in that organism’s genome that usually drives expression in only those cells. And that’s great, it works well, but there are a limited of characterized promoters, characterized tissue-specific promoters, that have this capacity to control gene expression so precisely. And so we looked at that, and we were like, well, we can use synthetic genetic circuits to take a limited number of tissue-specific promoters and combine their activities in new ways in order to generate new patterns of gene expression. So the circuits that we built perform Boolean logic operations. They can take two different tissue-specific promoters, for example, and then say, okay, we only want to express our gene of interest where those promoters are both on, in cells where those promoters are both on. And using this type of Boolean logic, we’re able to generate new patterns of gene expression, which we then use to control development, and we demonstrate in this paper that a combination if tissue-specific control and control over gene expression levels allow us to tune a single aspect of a plant’s root system. We can change how many root branches the plant makes, and that changes that we made don’t affect any other aspect of the plant. So it’s kind of allowing us to do a little bit of design of the structure of the organism. ERNIE: Jenn, it all sounds kind of mundane and esoteric until we get to the unbelievable implications of your work. Can you give us that incredibly exciting outlook? JENN: Yeah, we’re excited about controlling development in plants, controlling the size and shape of plants, because of how important the structure and the shape of the plant is for survival in a challenging environment. So unlike animals, plants can’t run away when conditions get bad, right. If it...
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    17 mins
  • FOCUS In Sound #36: Leenoy Meshulam
    Aug 29 2023
    FOCUS In Sound #36: Leenoy Meshulam Octopus during active sleep video: https://www.oist.jp/video/octopus-during-active-sleep Welcome to FOCUS In Sound, the podcast series from the FOCUS newsletter published by the Burroughs Wellcome Fund. I’m your host, science writer Ernie Hood. In this edition of FOCUS In Sound, we get to know a young researcher who in 2022 was the recipient of a Burroughs Wellcome Fund CASI award, the Career Awards at the Scientific Interface. Those awards recognize outstanding scientists who have made significant contributions at the interface of biology and quantitative sciences, bridging the gap between disciplines, and fostering innovation. It’s a five-year grant totaling $500,000. Leenoy Meshulam is a theoretical physicist who is also interested in biological phenomena, especially nervous systems and the brain. She explores the interface between physics and neuroscience. She received her PhD from Princeton University, after completing her master’s degree in physics and biology at Tel Aviv University. She is now a Swartz postdoctoral fellow at the University of Washington in Seattle. Leenoy’s research endeavors have already taken her in some fascinating directions, which we will hear all about, including a remarkable recent publication about the sleeping habits of octopuses. Leenoy Meshulam, welcome to FOCUS In Sound! LEENOY: Hi Ernie. It’s very nice to be here. ERNIE: Let’s start with your latest accomplishment as a co-author of a paper in the journal Nature called “Wake-like skin patterning and neural activity during octopus sleep.” Tell us about the overall findings… LEENOY: So this paper concentrates on a main finding where we saw that the octopus, much like in other animals, actually has two stages of sleep. So we managed to prove that every about hour the octopus goes into a different kind of stage of sleep—an active sleep bout, where similarly to REM sleep for humans, for example, the type of brain waves and the neural activity changes, and this is accompanied by a lot of color and pattern changes on the skin of the octopus while the octopus is still asleep. And so the way the cycle looks is, we have about an hour of sleep that is not the active part, and then a few minutes bout kind of like REM, with lots of color changes on the skin, different kind of neural activity that accompanies it, and then back to the stage that is most of the sleep. Something to keep in mind is that this is the first time that neural activity was recorded in this way in the brain of an octopus. So this is a sleeping octopus we managed to put a Neuropixel in, which means that there is an electrode inside the brain of the octopus that’s, we’re able to filter brainwaves out of to see what the signals look like. Also to see spikes in the brain of the octopus. And we can really see the activity of the brain while this is happening. So it’s both the underlying activity of sleep and the behavioral aspect of the two stages of sleep, and very high-resolution filming of the pattern changes on the skin of the octopus. The skin of the octopus is normally a system that we’re looking at for things like the camouflage of the octopus, right. This is why it has the ability to change so much color to have these coordinated, beautiful patterns that look like the coral reef that it is trying to match behind it. It also has texture changes there. And we just didn’t know before that this happens during the sleep of the octopus. So there are just these bouts of color changes that happen during sleep. ERNIE: So you were really able to correlate the visual and the brain phenomena? LEENOY: Exactly. So this is the underlying neural activity to this active sleep bout that makes it so interesting, because we can actually look at what is happening in the brain and show that this is really sleep. You can really see when you’re looking, if you look at the plotting in the paper, you can see the immediate, sharp transition into active sleep that is change in the neural activity, and if you’re looking at the brightness of the color of the body of the octopus, you can immediately see a drop, because it starts having color instead of being transparent. So the transition is immediate and is completely synchronized. ERNIE: Just so everyone is aware, we will post a link to video of the sleeping octopus along with this podcast. It’s well worth seeing! Leenoy, I understand that these findings point to the idea of convergent evolution. Would you elaborate? LEENOY: There are multiple elements of the system of the octopus that are similar to what we see in other animals. And because the cephalopods, which is the family the octopus is part of, so that’s cuttlefish, octopus, and squid—these are the cephalopods—the convergence in the evolutionary tree from us, for example, we’re talking 600 million years ago. That is around the time that on earth we moved from ...
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    28 mins
  • FOCUS In Sound #35: Michael Ferdig
    Aug 25 2023
    FOCUS In Sound #35: Michael Ferdig Welcome to FOCUS In Sound, the podcast series from the FOCUS newsletter published by the Burroughs Wellcome Fund. I’m your host, science writer Ernie Hood. In this edition of FOCUS In Sound, we welcome a biomedical scientist who in 2022 was the Burroughs Wellcome Fund’s first Resident Faculty Scholar. Michael Ferdig is a Professor of Biological Sciences at the University of Notre Dame, where he has been on the faculty since 2001. He specializes in the genetics and genomics of drug resistance and virulence in the malaria parasite. Malaria is a parasitic infection transmitted by the Anopheles mosquito. Malaria drug resistance is an ongoing topic of major importance in global public health, where the disease is still a significant worldwide contributor to mortality, with nearly a half-million deaths annually. Mike received his BS and MS degrees from the University of Nebraska-Lincoln, his PhD from the University of Wisconsin-Madison, where he also served a postdoctoral fellowship. He also did a postdoc at the National Institute of Allergy and Infectious Diseases from 1997 to 2001. Michael Ferdig, welcome to FOCUS In Sound! MIKE: Oh it’s a pleasure to be here, nice to meet you, Ernie. ERNIE: Mike, there is so much for us to talk about, but I’d like to start with what brought you to the Burroughs Wellcome Fund to be its first Resident Faculty Scholar… MIKE: Well, I love the question, because it makes me smile. I was sitting up there in South Bend, Indiana with the fall season approaching, and going into another teaching semester, and putting in another load of grants, trying to get them renewed. And I was in this mental place of, you know, getting to this place in my career where I’ve had plenty of success and things are going well, and I just felt like I was turning the crank and perpetuating myself, and looking around and realizing, in my business, in the business of academic research science, it tends to be what we do. We get to a career place where we almost are content to settle into this safe bubble of self-perpetuation. And I had almost a little bit of a panic about, oh no, is this it? And it happened to be at the same time I was noticing that—I was familiar with the Burroughs Wellcome Fund, just like we are out there as scientists—had just announced this Resident Faculty Scholar. And I thought, this is what I need to do. I need to step away. I had been 20 years at Notre Dame with no request for leave or what they call sabbatical sometimes, and I thought, I need a place where I’m not just going to go make more versions of me, I’m going to go try to find the next version of me, and sort of move into this later phase of my career, and hopefully do things a little more useful and interesting. So it was just kind of magic how it all fell together, I reached out. I had known Victoria McGovern at the Fund for years. She had long been an advocate for infectious disease research, and she said, “Oh yeah, by the way, we do have this fellowship, why don’t you look into it and see if it might fit?” So I applied, and a summertime later, there I was. ERNIE: I know Mike it’s been quite a formative experience for you. Can you tell us a little bit more about some of your activities during the scholarship? Did you have a specific project that you worked on during the sabbatical? MIKE: I did. As imagined in the first place, I do need to strengthen my program, basically I wanted to expand and extend my lab science. We’ve always been what they call bench scientists, experimentalists in the lab. But I work on malaria, which is an organism that infects people around the world and has caused devastating disease for millennia, and I really feel the need to move my work towards the field. So that kind of relevance and extending. But I’d also really noticed, I do a lot of teaching, a lot of moving toward more administrative roles, and I just noticed that this problem of needing to bust out of our bubble, out of our cocoon, was really pervasive across all the things I was working on. So I set up some aims. Aim One of my project was just very literally to take what we do in the lab and move it into a more field and clinical relevant place. Which is a pretty big, it’s a very different way of doing our workaday. And I knew down here in the Triangle, there are some really good researchers who do more clinical work in the malaria world, so I thought, a-ha, this would be a great chance to pull some of those people together, bring in some outside experts, the people I admire and respect, and sort of bring everybody together, and it just has been amazing how things fell into place. And then I had a little more aspirational goals, and one was getting more out of my immediate research focus into where is the field going, what is malaria, [what does] the future of malaria research look like? And these are more community oriented, open science...
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    30 mins
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