JESSE: I want to transition a little bit and talk a little bit about your research. It seems like from your kind of CV background page you sent me you've done a lot of different things. I will probably have to stop you at various points and ask explanations on various pieces of jargon, as I try to work my way through what you done. So, can you start with what you worked on as your dissertation for your Ph.D. and we’ll kind of try to move forward from there or hit the high points, I guess? CHERYL: Sure. So, I did-- I will preface this by saying I did wind up doing my Ph.D. postdoc and then my current position all at Penn State University. That was not my original plan is discouraged, especially in life sciences and some other fields as well to stay in the same spot. This considered that you are not really broadening your horizons and your ability to contribute intellectually could decrease the longer you're staying at a certain place, but I stayed-- I made the decision to stay for personal reasons. You know, I met my future husband as I was finishing up my Ph.D. So, that's why I stayed and I'm fine with my choices in that respect. So, when I was in-- did my Ph.D. I studied muscle development in fruit flies. And the first thing that a lot of people are like “Oh, muscles? Fruit flies have muscles?” But they fly, they walk so yeah. And we specifically studied embryonic muscle development, so that the muscles that would form when it's a developing embryo, and that the larva would use to crawl around on the meat or whatever they're going to eat. And I studied a gene called Nautilus. And what we realized that that gene does, they’re several they called paralogs. And what that means is related genes in like vertebrates, and they're like muscle regulatory factors. And we, the gene that we studied ?? 02:11> was responsible for differentiation of muscle precursors. So, when muscles are first forming, they don't look like a muscle, they don't look like a ?? 02:22> muscle, right, it just looks like a round cell that might express some muscle proteins like myosin and actin, but when you're actually differentiating or forming into the more mature muscle type, what are the genes responsible for that process? And we found that this gene Nautilus that I worked on, was responsible for a subset of muscle differentiation in the embryo. And we used a variety of different approaches, a lot of genetics and molecular biology. I did a lot of microscopy during that time, so I really felt like it was a really good experience. I felt like I learned a lot. And I came out of there though, and kind of wanted to switch things up a little bit. Like I said, I stayed here at Penn State, so I wanted to broaden my knowledge and my experience bases as much as possible. So, I actually switched-- I did switch fields. Some people will actually stay in the same field that they get their Ph.D. in. And for me, I decided to switch and did gab receptors in mice. And gab receptors are responsible for the majority of inhibitory neurotransmission in the central nervous system. So, to kind of calm things down, right. And so that again, was-- I did a lot of work with mouse neurons, primary mouse neurons that we had to dissect out of these tiny little 14 day embryos, which I felt very bad about. But the worst thing actually was when I was doing these mouse dissections is doing these with little forceps and I had to do it under a dissecting scope. And every time we did dissections, I could not drink any caffeine that morning. That was probably the worst thing about it, right? I was like, I really want a cup of coffee, but it was so tiny that you really did not have the control to really get in there and do these dissections. JESSE: So, your dexterity would be affected by the caffeine ?? 04:30> CHERYL: Yeah, I mean, because not any noticeable. It's not like I would notice it if I was taking notes with a pencil or doing anything else. But when you're actually trying to dissect really, really small things under a microscope, it is just enough that you did you lost a little bit of that control. So, that was-- but I studied that for a couple years and I wound up studying this one, so that these gab receptors, the gamma unit, so the gap receptors are made up of a number of different proteins that together form the receptor. And one of those proteins is gamma sub unit. And I worked on trying to find various proteins that might interact with this gamma subunit to try and control-- just to try and learn more about how these gab receptors cluster in synapses. So, what you in general, right, so receptors, neuron receptors will be at synapses, where you have an axon, and then you have your dendrite, and your receptors will cluster together underneath the axon to receive input. And what we were trying to figure out is what are the mechanisms behind the clustering of these gab receptors at synapses. And so I did some screens to look for interacting proteins and I discovered the first mammalian ?? 06:02> transferees. And what that means is, it is an enzyme that attaches - group which is a fatty acid to this gamma subunit which would then affect its clustering. It would allow-- affect how the receptor gets to the cell surface and gets recycled back and so forth. So, that's sort of what I worked on as a postdoc. So, I kind of I did a couple ?? 06:31> switching model system, worked with fruit flies and I worked with mice, and I enjoyed both those things. And after that, I kind of felt like I needed a break from academia and I thought, oh, I just, I need to kind of get out here and see what else is out there. Unfortunately a year in State College, Pennsylvania, I mean, Penn State is the largest employer of science people. There are few companies around There's really not a lot of options as if there would be in a bigger city where there might be pharmaceutical companies or biotech, and we just don't really have that here. But I did work for a small company who did mitochondrial DNA forensics. So, this is back, 2004 and we tried to remember when the human genome was sequenced, I want to say 2001. JESSE: That's what I wanted to say offhand. But I would trust you more than me on that. CHERYL: Say that, around that, yeah, a little before that, but it really wasn't-- Nowadays, you can do whole genome sequencing pretty fast. In fact, that's what I do for a living now, but its DNA sequencing, but back then it was harder to sequence DNA from blood and so forth. But the other thing too is that mitochondria, so red blood cells do not have mitochondria-- Well, they don't have nuclei. So, you have if you wanted to isolate DNA from red blood cells, you could get mitochondrial DNA, but you're not going to get your nuclei gene, so genomic DNA. But anyway, we would-- So, a lot of what we would do would be to get, like samples of bone and hair in. Especially like hair samples, and a lot of it was cold cases where we would isolate mitochondrial DNA from old hair samples and a lot of it was trying to more like exclude people as being, you know, exclude people from committing the crime, right, so where they get convicted and based on some evidence. But there was not any DNA evidence and there might have been some old hair samples or blood samples or something from the case and a lot of times, we would test those and look to see whether they were a match to the person who was being accused of the crime. So, it kinda, it was interesting. I learned a lot about quality control at that point and really taking-- Not that I was not careful as a scientist, but when you're thinking that you might have somebody’s, not actual survival life on the line, but their livelihood in terms of whether or not this person is in jail or not, right, you realize you take a lot of responsibility for that and be like, wow, I am really affecting-- potentially really affect somebody's life. And I think it really kind of stepped up my awareness in terms of sample handling and quality control and things like that. So, I think that actually, that made for pretty good, for me, a good transition to my current position, which I’ll go into a minute. But I actually wound up after I left there, I took a couple years off from that. I sort of stayed at home and worked part-time when I had my son in 2005. And I never really left science. I taught a couple of classes in the evening, a couple of molecular biology classes, and I did some freelance work for some publishing companies, where I wrote some test questions for online material, studying material and things like that. Before then I got my current position as an associate research professor, and we study blood cell development. And mostly I do a lot of DNA sequencing, which is really kind of fun. JESSE: So, I want to back up a little bit. You were talking about--
Smart Athlete Podcast Ep. 39 - Dr. Cheryl Keller Capone - GENOME SEQUENCING - Part 2 of 3
I want to transition a little bit and talk a little bit about your research. It seems like from your kind of CV background page you sent me you've done a lot of different things. I will probably have to stop you at various points and ask explanations on various pieces of jargon, as I try to work my way through what you done.