FOCUS In Sound #37: Jennifer Brophy

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...