The Power of Genetics with Robin Cooper

The Power of Genetics with Robin Cooper - Podcast Transcript

Have you ever wondered who was doing the research that will impact your future? The research podcast lets you met those people, and learn how the University of Kentucky is exploring and strengthening our understanding of the world through research and discovery.   

Here's Alicia Gregory, director of Research Communications. 

Alicia: Today we’ll meet Robin Cooper, an associate professor of biology in the UK College of Arts & Sciences. He talks about his genetic research with fruit flies and crayfish. And Cooper shares what his work has in common with Nobel Prize winner Thomas Hunt Morgan.

Robin Cooper: So as you’re whacking around these fruit flies that are flying around the lab, you can see our primary research animals is a fruit fly, Drosophila melanogaster, and another animal that we use in the lab are crayfish. And those are the primary research organisms we use. The fruit fly, as you might know and many people have recognized the department of biology, because we call this the Thomas Hunt Morgan School of Biological Sciences. We changed it from a school to a department a while, a number of years back. But it is still the Thomas Hunt Morgan building that we’re in right now. This is because Thomas Hunt Morgan was an undergraduate at the University of Kentucky, and then he went on for graduate work and he was awarded the Nobel Prize, working with Drosophila as a model organism.

A lot of people don’t realize though, Thomas Hunt Morgan, some of his first work was actually on regeneration in crustaceans. So he was interested in the regeneration of limbs in crustaceans. So I kind of find this a bit interesting that we’re working with crustaceans, as well as fruit flies, and it’s the same as what Thomas Hunt Morgan used 100 years ago, but we’re not in such the old research questions, more modern research questions. But the power of genetics allows us to work with the Drosophila and do things really you can’t do with any other organism, in the sense of rapid development, manipulate genes very quickly, and test out many different aspects from behavior to how the neuro circuits are formed. And you can relate whole animal behavior to the mechanisms behind that behavior, and I think that’s really the power of a lot with the genetics with fruit flies. The crayfish is just a really nice preparation to understand some of the physiological principles.

Robin Cooper: In particular, we are interested in synaptic transmission. And our past NSF funding has been looking at the differences in high-output and low-output communication between synapses, such as when a nerve communicates to a muscle, or to another nerve, there are differences in the synaptic structure, and the proteins involved. So we- we’re interested in understanding that difference in high-output, low-output synapses, but also how they could be modulated differently. So, as an example, you think about the human brain, and you might have heard about people on medications, maybe anti-depressants for example, like prozac or fluoxetine, that can alter the mood of somebody, but mechanistically how does that work? And does it work on all synapses the same way?

We’re a much more complex organism in our brain as well; the fruit fly and crayfish the reductionists approach. But we can address some of the same principles as these organisms and then see how they translate to humans, for example. But our work in the lab for the last 20 years is basically on basic science and understand these fundamental principles, and people can extract information from that.

For example, the fruit fly, I think now that the count is up to about 60 human diseases that are now modeled in Drosophila. Everything, from diabetes to neurological issues, learning and memory for example. Can they be treated? Can they be modified? And those are some of the fundamental questions we are interested in. We also like to play around and I think that’s really important to play in the lab for undergraduate and graduate students because when they play on something a little bit different outside of the primary goals, they learn new things and they come up with new questions.

Robin Cooper: For example, we had this one undergraduate a number of years back, Nick Badre. He was just phenomenal. He asked a simple question about why is it that CO2 knocks out Drosophila, and I said, “Well, I really don’t know.” So we went around and asked some of the geneticists around the department, and as well as elsewhere, and nobody had an answer for the mechanism. Here’s this undergraduate freshman, he was in my freshman class, 350 students in this room he sat right up front. He asked these questions every day in class, and I said, “oh my gosh, I’m never going to get through this lecture.” But it was very good, and afterwards he came and asked could I work in the lab? And with his inquire and just inquisitive nature I said “of course.” I think he published three papers from the lab as his undergraduate work and first author on some, that we followed up on some of that research and it’s led to new things. Actually we put in an NSF proposal, a grant proposal, based on some of the findings that we had from that project relating to CO2 and ph differences, and intercellular as well extracellular environments and how those influence synaptic transmission. So it’s been really, you know, engaging, you have to keep an open mind and listen to people’s questions and wonder can I really answer that or just not to negate it but actually think about what these students are interested in.

Robin Cooper: Some of the most exciting results we’ve had recently was with some new techniques that we started in the lab. And it’s just gone every direction actually. It is called optogenetics. And it is where you can take a gene from say a blue-green algae, and people have been able to put that into the Drosophila genome and that gene expresses a protein that is sensitive to light. An example is that the one that were using is chandler rhodopsin, and that is sensitive to blue light, and there are some other proteins that are sensitive to different wave lengths, that you can target that particular gene to very defined cells. In our case, we are looking at neurons that express and produce serotonin, or dopamine, or acetylcholine. These are neurotransmitters but also neuromodulators. And if we go back to our interest is on modulating synaptic transmission, these give us a lot of power of, in the intact animal you can shine blue light on the animal and then activate just their serotonergic neurons. So instead of using pharmacological approaches, it can use more of an intrinsic approach, activate that neuron, and then see how that changes the animals’ behavior.

What’s really quite interesting about this is that what about during development? If we altered the serotonergic pathways, or the level of serotonin being released, how does that affect the neuro circuit, the formation? Now we’re looking at it at a basic science level, but you think about maybe a mother that just gave birth and she’s undergoing postpartum depression. And she needs to take an anti-depressant, like fluoxetine or Prozac. Some pediatricians say it doesn’t really matter that much if you wanted to keep breastfeeding, and we know that Prozac will get into the breast milk. What are the impacts on that fetal development?

And these are the questions that people haven’t really addressed yet fully, it’s very complex in a human system because the brain’s so complex. Behavioral changes might take years to actually manifest themselves. Learning deficits in school, for example, or maybe social behaviors. And so those are very fine subtle affects that are hard to pick out in a human population, also in animal models, but at least we can address some of the very pronounced effects. If a serotonergic neuron is stimulated and it’s releasing a lot of serotonin. If the target cell doesn’t branch as much because it is getting so much activity, that’s a structural change that we can pick up. And so with optogenetics, we are able to target these particular neurons like serotonin, dopamine, acetylcholine, look at changes in behavior of the animal, as well as developmental aspects.  

Robin Cooper: What’s been fun about this for us as a research tool we have actually taken it out to schools. So we have a paper we’re working on right now where we’re putting that out for teachers, science teachers. We published a paper two years ago that went into the national Science Teacher, so every high school science teacher in the U.S. gets this journal. It is called The Science Teacher. And actually it’s been quite interesting, because that paper has resulted in more emails and more questions than any primary research paper that we’ve actually put out. So here I think that has had a very large impact, and Cole and myself, and past graduate students, have actually gone out to schools. We’ve gone out to Dunbar here in town. We’ve gone to duPont Manual in Louisville. We’ve gone to Louis County High School, Garrard County, Lancaster High, and Somerset High recently, and actually worked with their high school classes for those teachers then to use this technique. So it’s cheap. We’ve had students ask their own questions, and then be able to follow up on primary research with this.

So I think these latest techniques available to the researchers with optogenetics and using Drosophila has really been kind of the new changes that we’ve been pursuing, and it’s just- it’s fun!

Robin Cooper: Some of the work we’ve done too with another graduate student is looking at the effects of the heart with optogentics. What is really interesting about this is in flies, you can have this blue-green algae protein expressed in the heart of Drosophila you can shine the blue light on it and the heart will beat faster. So we think about what’s happening with humans, for example. Right now if we put a pacemaker on a human heart, or even a ventricular pacemaker, they sew those on to the heart, and it some cases that can actually cause injury on the heart tissue.

Now those are life, you know, needed implementations for the people, but think about what one could do with optogenetics. If one could express these proteins in the heart with a virus for example, and there are examples of this being used in rodent models already, then all one has to do is shine a light on and off, on and off, and you could actually pace the heart. We’ve used the Drosophila as proof of concept. When we put that publication in for review, the editor actual wrote back and said, “Oh, this is a wonderful technique that you’ve been able to show. We’re going to get this reviewed very quickly.” And I think it only took about a week in the review process and it was out, so I think the community is really excited about this as well.

Robin Cooper: I’m going on my 21st year here at the university. The past 20 years has been just wonderful. Wonderful graduate students, undergraduates to work with, and I think that has been the real joy the last 20 years. When you get to see an undergraduate, not just in your classes that you’re teaching, but in the lab primarily, when you see an undergraduate say “Oh I get it” and they are poking an electrode inside of a cell and they finally measure an action potential that looks just like the textbook, and you hear them say, “Wow, that’s just like my textbook figure.” Yeah, where do you think it comes from (laughter)? So it’s great when they get to see these results that they’re able to obtain themselves, and then it really empowers them and they’re encouraged to continue to go on with their research.

In the 20 years I’ve been here, I think we have about 150 publications, 50 of those are actually with undergraduates as first author or co-author on our papers. So we’ve published papers, I think three or four now, with high school student’s names on the paper. Our last paper was actually with a high school student as first author. And it’s kind of interesting because she developed a new saline that is used to keep the Drosophila heart alive, so we can do experimentation with it. Well, I was invited to a seminar to give a talk in Krakow, Poland, with an international physiology conference, it’s only once every four years. So this person emailed me and then I didn’t respond back right away, so she called me, was from Poland, they said, “We would like for you to come and present this research on this latest paper that you just put out.” I said, “I really can’t make that particular time for the meeting, how about if I send my high school student that’s been working on this project.” She said, “Oh no, a high school student. We want to understand about the latest saline that you developed,” and I said, “Well, she is first author on the paper. She’s the one that developed it.” And so she was really quite taken aback. But she actually went to Poland and she presented her research at this international meeting with people from all over the world. I heard back from the people that were there and said, “I’m so glad you sent her, she was just a wonderful person” and the presentation that she gave, an oral presentation, went over really well. And so promoting the students, if it’s their project, they take it and embrace it and you know they’re engaged. This is another example of keeping people, you know, engaged in their research and spark their interest.

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