Voices Shell === [00:00:00] Agus Munoz-Garcia: And studying animals in the wild is not easy. You have to go to the places find the animals, sometimes catch them do different measurements, et cetera, and then in the lab you have to do other things. But actually, I can tell you that the reward is unbelievable though. So once you complete a research project and you are done and then you take a look at the data and you analyze it... at least in my case, so the level of satisfaction that I get from that is really unbelievable. Jen Farmer: From the heart of the Ohio State University on the Oval, this is Voices of Excellence from the College of Arts and Sciences, with your host David Staley. Voices focuses on the innovative work of Arts and Sciences faculty and staff. With departments as wide ranging as art, astronomy, chemistry and biochemistry, physics, emergent materials and mathematics, and languages, among many others, the college always has something exciting happening. [00:01:00] Join us to find out what's new, now. David Staley: I am pleased to welcome today Agus Munoz-Garcia over Zoom. He is an Associate Professor in the Department of Evolution, Ecology, and Organismal Biology at the Ohio State University Mansfield Campus. He is a physiological ecologist, and I wanna find out a bit more about what that might mean. Dr. Munoz-Garcia, welcome to Voices. Agus Munoz-Garcia: Thank you. David Staley: And that is my first question. Tell us what a physiological ecologist is. I think I know those terms separately. I don't know what they mean together. Agus Munoz-Garcia: The combination of them, yes. Physiology is basically the study of how organisms work. I'm an animal physiologist, so I'm interested in knowing what happens in the body of animals to do whatever they do. So for example, when you eat an apple, for example, so animals are going to get nutrients out of the apple, right, and then they're going to use these nutrients for different things. So I study the processes [00:02:00] that allow animals, first, to extract the nutrients of the apple once the animals absorb these nutrients, so what do they do with them, et cetera, things like that. So, my main interest is basically to study processes that lead to energy balance and water balance in animals, and then the ecology part comes from the fact that classic physiologists, so they study these kinds of things in the lab, so they use animals, they rear them in the lab, they are interested in getting individuals that are actually basically as close as possible to each other, so sometimes, ideally, if, even if they can get clones of the individuals that's best. And these physiologists, so they are interested basically in knowing what are the exact mechanisms, what are the molecules that participate in those processes? How the cells do the things that they do? Physiological ecology. I'm [00:03:00] interested in knowing how animals do all these kinds of things, but in the wild, and there is a lot of diversity, right between, across a species, but also within a species. Every individual is different and physiologists that actually do studies in the lab, they are more interested about finding average processes, this mechanism is like this in all the individuals of these species. I'm actually interested in the variations of these mechanisms that you find among individuals and how natural selection, for example, has shaped all these processes in animals in different environments. So, basically what I am trying to do is to study the interaction between the physiological processes that occur in an animal, how the animal works in relationship with the natural environment in which the animal lives, and that's basically what physiological ecology means. David Staley: In terms of methods, in terms of techniques, what are the, I guess the [00:04:00] challenges of studying animals in the wild versus a lab, versus like a controlled lab setting? Agus Munoz-Garcia: It is more difficult, more challenging because I have, for example, two components in my research, right? So I do field work, but I also do lab work, and then you have to know pretty much a little bit of everything. And studying animals in the wild is not easy. You have to go to the places, find the animals, sometimes catch them, do different measurements, et cetera, and then in the lab you have to do other things. But basically, you have to be proficient in different kinds of methodologies, and to put together all the data that we have is also a challenge. So, when it comes to the analysis of the data and the interpretation of the data it's also more difficult. But actually, I can tell you that the reward is unbelievable though, so, once you complete a research project and you are done and then you take a look at the data and you analyze it, at least in my [00:05:00] case, so the level of satisfaction that I get from that is really unbelievable, so. David Staley: I've been avoiding this, and I was saying before we started recording I came to this interview with a little bit of trepidation. So you study cockroaches, and my first question is, why do you study cockroaches? Agus Munoz-Garcia: The subject of my research right now is a process that is called resource allocation. So for example, you have eaten lunch, I'm assuming. I hope you have. David Staley: I have indeed. In fact, I've had an apple today. Agus Munoz-Garcia: So in animals they get food, right? And then what do you think is happening with the food that you ate today? So once you intake the food, so your digestive system digests the food, which just means to break it down into smaller molecules that we can absorb, right? Then you absorb all these nutrients, as many nutrients as you can from the food items. What do you think it happens with these nutrients once you [00:06:00] absorb them? What are the things that you do with the nutrients? David Staley: I assume my body uses them to perform functions. Agus Munoz-Garcia: So, you have some nutrients are going to be used to get energy out of them, right? David Staley: Sure. Agus Munoz-Garcia: Some nutrients, you don't get energy out of them. You use them to build the structures, like for example, you build muscle, for example. Some other nutrients, sometimes you get an excess of nutrients and then you need to store them in different organs in your body for later use whenever you don't have availability of these resources, right? So, basically your body is taking these resources and then is allocating these resources to different tasks, and there are five main tasks that animals can put resources into it. So, one task is basically what we call maintenance of homeostasis; this is a fancy word to say that we need to remain alive, so [00:07:00] housekeeping. Then another task is growth. Some animals, they grow during all of their lives, humans don't do that, but there is a time during our lives in which we put resources into growth. You need also to put resources into locomotion, right, so we move, we do different kinds of activities that require movement. Then if we get an excess of nutrients, we store these nutrients in different organs, and then you have to put some energy storing these resources. And we also put resources into reproduction. So there are these five main tasks that all animals have to do, and normally these resources, they are not unlimited in nature, right, so your body has to decide, where do you put the nutrients depending on the situations in which you are into, so depending on environmental conditions, you can decide to put more resources into reproduction and less resources into growth, for example. [00:08:00] And depending on the environmental conditions, then you can decide that in next month I'm going to change the allocation of resources. That's a little bit like what we do every day with our budgets, right? And I get a salary and my salary obviously is not unlimited, right? So I can, I need to make decisions. So, if I want to live in a mansion, that's okay, but then probably I'm not gonna have enough money to put into really fancy foods, for example, right, or a very nice car. So, you need to make these decisions and animals do that. And we call this processes allocation of resources or resource allocation. So how does your body decide? So, after you ate your lunch, then you get these nutrients and your body decided to put some nutrients into this, into that, so how does your body decide to put nutrients into, let's say, locomotion and not growth? So for example, I'm not particularly tall, I would [00:09:00] like to add a couple of inches to my height, but I cannot decide that consciously, right? So how does my body decide that the lunch that I ate today, all these resources they have to go to locomotion, maintenance and reproduction, let's say, and not to growth? The answer is that nobody really knows, and this is what I'm studying. David Staley: Do we have any at least preliminary conclusions as to why that might be? Agus Munoz-Garcia: So to answer your previous question, so I use these cockroaches as my model organism because it's very easy to work with them and it's very easy to track these allocation of resources. So, I have to say that when I say that I work with cockroaches, people get this reaction that you had before. There are more or less 60,000 species of cockroaches in the world, and this one is actually very special. It is not like the cockroach that you can find in your kitchen, these big cockroaches that are gross, right, and that [00:10:00] more or less, everybody who is a human being, basically, you are either scared or repulsed by them. So these cockroaches, they are small, they are maybe half an inch in length, and the interesting thing about these cockroaches is that they are viviparous, that's their mode of reproduction. So what does that mean? It means that all the species of cockroach in the world, they are of oviparous, which means that they to reproduce the females lay eggs, and then once the females lay the eggs, then they abandon the eggs, right, so then the eggs hatch, and then you have these little baby cockroaches, we call those nymphs. And then the nymphs basically disperse and they can go, they go on with their lives. This cockroach is the scientific name of this cockroach is Diploptera punctata. These cockroaches, they are native from southeast Asia and the some Pacific Islands, including Hawaii, by the way, they live in Hawaii. And what is interesting about them is that they're not oviparous, [00:11:00] they don't produce eggs, they are viviparous. So, what this means is that the female produces the embryos, right, and the embryos, they stay in the abdomen of the female inside a kind of bag is an organ that is similar to a bag, and we call this organ the brood sac. And the brood sac is, will be basically the equivalent of the uterus in human females. And then the embryos, they stay there. Now the females of Diploptera punctata, what they do is in the epithelium, the lining of this brood sac, they make this secretion, alright, and this secretion contains proteins, fats, sugars, and the composition of this secretion is very similar to the milk of that mammals produce. In actually, we call that the milk that the cockroaches secrete. So the cockroaches secrete this milk, and then the embryos are eating this milk during their development. So the embryos [00:12:00] stay in the brood sac for a couple of months, more or less, and then the females give birth to 10, 12 nymphs, and that's basically what viviparous mode of reproduction means. You can see that is exactly the same as humans and most mammals do. So, what makes these species really interesting is that fact. We have colonies in the lab of thousands of individuals, and whenever we need to do an experiment, then we select some individuals and we put them under different environmental conditions. And the nice thing about studying resource allocation in these animals is that we have very large sample sizes for all the experiments that we do, and it's very easy to work with them. They are very easy to maintain. They eat dog food, they drink water, and we don't need really to change anything. We have these groups of individuals, big groups of individuals in [00:13:00] containers, right, and the only thing that we need to do is twice a week change the water, make sure that they have enough food, and pretty much that's it. So, it's an animal that is very easy to maintain as opposed to, I dunno, lab mice or lab rats that need constant attention. They need hours a day to just to maintain, right, and clean the cages, et cetera, et cetera, and every day, weekends included, holidays, et cetera. So these animals are very easy to maintain in captivity, and it's very easy to track resource allocation in these animals. So what we do is do we measure the amount of food that they eat in given time intervals. We also have in the lab instruments that allow us to measure the energy expenditure of these animals. We do that regularly, every 15 days or so, we measure all of the animals that we have that are part of an experiment, and then we have a very accurate measurement of the amount of energy that they spend. And also we give them food that [00:14:00] we spike with some molecules that actually we can trace later. So, whenever they eat, we know how much they eat, but also we know where the nutrients go to the different organs. And all these measurements combined allow us to know where the resources have been allocated. So, we expose the environmental condition that we use in our experiments, we tried with different environment, kinds of environmental conditions, but actually the environmental factor that we're actually using in our experiments now is food quality. So, we have basically animals that eat dog food, they love it, and actually the dog food has all the nutrients that they need to survive and reproduce, and they're very happy with it, and then what we do is we mix the dog food with cellulose. Cellulose is a molecule that cannot really be digested, cockroaches, they have some microbes in the gut that can digest cellulose, but actually they're not very effective. So, basically [00:15:00] when we mix the dog food with 50% cellulose, basically we are diluting the food by a half, they get half of the nutrients that they will get if they eat the same amount of food, but if it's all dog food. And what we do is we create these diets, right, so we mix the dog food and the cellulose in different proportions, and then we feed the animals to different diets depending on the experiment, and then we study resource allocation, the patterns of resource allocation of the females and their different diets. So, then we can study when the females eat this particular diet, do they change the pattern of resource allocation, do they put more resources into maintenance, do they put more resources into reproduction, et cetera? And we have preliminary results now that indicate that yes, the patterns of resource allocation are different, and what we have seen is that in environments that are not very good, the main pattern that we have detected is that in environments that [00:16:00] animals perceive as not being very good, their metabolic rates decrease, their energy expenditure decreases, so they enter these conservative mode, right, and they put less resources into reproduction. David Staley: You compared these cockroaches to like lab mice or lab rats: is the implication that by studying cockroaches you can learn something, maybe, about human resource allocation? Agus Munoz-Garcia: Yes. So lab mice and lab rats and other species of animals, they are used as what we call in the scientific community model organisms. So ,those are organisms that are sometimes even designed, you control the genes that these animals express, et cetera, et cetera. So, these model organisms are used by lots of scientists to study many different kinds of things. My model organism are these cockroaches. So, there are very few labs that actually use these animals. When we study, when we get the [00:17:00] results from resource allocation and all the studies that we do, we try to establish comparisons ,so we wanna know also if the patterns that we see in these cockroach are equivalent to the patterns that you see in other species of animals, because in the end, I'm not particularly interested in knowing where do cockroaches put resources into, so, this question is not that interesting to me in the sense that, okay, if you can only apply your results to one species, then that's not very interesting to me, to be honest. So, when we use model organisms, it's because we cannot study lots of species in general, right? So, we use these model organisms, we study these processes in these organisms with the hope that what whatever we learn from these organisms is going to be applicable to most of the species that we have in the world. So, I know that these cockroaches, they are insects, lab mice and lab rats are vertebrates, mammals, they are very different classes of animals, [00:18:00] but what we are after is to find like these physiological processes that operate in pretty much all animals that can explain the same results that we get from all these species, no matter which is the species that you study. If you know these mechanism is general mechanisms, then it's very powerful to basically study the interactions between the organisms, even ecosystem dynamics. By studying one organism and studying the physiological processes of that organism, then you can go at higher levels of biological organizations, so you can go from cells to organisms, to species, and to groups of species and even ecosystems. That's basically what we are after. I know that it sounds very ambitious because it is, but in my lab we go after this integration of different biological levels of organization that can [00:19:00] explain basically what are the factors that actually matter in shaping the way in which organisms work, but not just restricted to one species. We are trying to find general patterns that can be applicable to pretty much all organisms. David Staley: I know that one of the big potential applications of your work is in cancer research. Could you say, say a little more about this? Agus Munoz-Garcia: Yes, of course. So, remember that I told you that people don't really know how animals or individuals decide where to put the resources? So we have these hypothesis, cells, I have to explain a little bit about what a cell is and what cells do. Animals are made of cells, basically, the cells are the units that form basically the tissues and the organs of the animals, right, and we have many different kinds of cells. When you take an individual cell, each individual cell uses energy and resources to produce a particular individual, a particular cellular [00:20:00] response. So for example, your muscle cells, that responses to contract and when you have lots of muscle cells forming muscle, the contraction of all the cells allows the muscle to contract, and the contraction of the muscle allows you to move, for example. There are other cells that do many other different things. So, the cells in the reproductive system, for example, there are some cells that they can proliferate and they become an embryo. So, you have different cells in different organs that are going to do different things. But to do the things that these cells are specialized in doing, they need resources and they need to produce energy, right? So, the body in animals that are formed by millions and millions of cells, most animals, right, the insects, vertebras, et cetera. So you need a coordination of where do you want to bring the resources, right? So, all the cells are gonna want their share of resources, right, [00:21:00] but remember that the resources are limited, so there has to be some kind of coordination that tells these cells, okay, so now you are active, so okay, I'm gonna give you more resources. And all these cells that are in organs that are not active now, yeah, you are not gonna get as many resources now, but don't worry, whenever you become active, then you're gonna get more resources. Somebody has to coordinate and somebody has to give. So, the cells are gonna have different demands for nutrients and energy depending on what they are doing, right, and somebody has to control the supply of nutrients to the cells, depending on their activity levels, right? For example, if you wanna put resources into reproduction, then your cells in the reproductive system are going to become very active, and then the body is going to send more resources to these cells because when they are more active, they're going to need more nutrients, so you need to bring more nutrients to these cells. This normally happens at the expense of other cells. [00:22:00] You cannot put energy and resources into all the tasks that you can imagine because you have a limited amount of resources normally, especially in nature, right, so somebody has to decide where the resources go and make some cells happy and make some cells not as happy. Okay, so the organ systems that actually coordinate these things in vertebrates and in insects too, are the nervous system and also the endocrine system. The endocrine system is a system of organs that is formed by glands that secrete hormones, right? The secretion of hormones and the nervous system are going to adjust this supply of nutrients to different organs depending on the needs of the different organs. Now, they do that at the cellular level, right? Then if you distribute the nutrients, so for example, if the cells in the reproductive system, they need more nutrients and you send more nutrients to them, but then you put [00:23:00] less nutrients into growth because you are sending lots of nutrients into reproduction. So at the organ level, you are adjusting the flow of nutrients, right, but what do you see at the whole organism level? What you see at the whole organism level is that the organism is changing its pattern of resource allocation, is putting resources into reproduction and not into growth. Now, how do the individual cells understand these messages? Whenever the hormones are secreted or the nervous system tells a cell what to do, or it brings nutrients to the cell, when you look at an individual cell, the cells have these molecules that act like a sensor molecules, they detect what's going on in their surroundings. And the cells are formed basically by lots of proteins, lots of different classes of proteins. Proteins are molecules that you find in cells that actually do the jobs that cells do, and when the cells detect their [00:24:00] surroundings, for example, they see that there are lots of nutrients, then the cells, they control the expression of some genes to use these nutrients. And the genes are basically sequences of DNA, they are like small books that contain instructions on how to do some stuff. So, for example, if you wanna know how to drive, you can read a manual and then you learn how to drive. So the genes are like tiny manuals that the cell has, and when the cell needs to produce energy, for example, okay, I'm going to express these genes, which means basically I'm going to get these books, open them, and then know how to produce energy, or if the cell needs to produce a particular protein, then you take the gene that codes for that particular protein, and then you express it, you activate that. It turns out that this job of regulating the [00:25:00] expression of genes is done by these groups of proteins, right, that tell other proteins what to do. So, there is like a hierarchy. The proteins that tell other proteins what to do, they are called regulatory proteins. There are a few classes of regulatory proteins only and they are activated or deactivated depending on some environmental conditions, so for example, under environmental conditions of temperature, there is a family of regulatory proteins that is activated and then the cell responds in a particular way. If it's too cold, the cell responds in a particular way, if it's too hot, the cells responds in a particular way, and all this is driven by the regulatory proteins which can feel the environment and then tell other proteins in the cell what to do. So, remember that this happens at the cellular level, right? When you have lots of cells that are doing more or less the same thing, then you get the response at the organ level, right? So, we have [00:26:00] found that there are these proteins that are regulatory proteins, they are called sirtuins, and these regulatory proteins, they are activated depending on the nutritional status of the cell. So, when there are lots of nutrients around the cell, then they are activated when, there are less nutrients, then they are deactivated, and then by getting activated or deactivated, then they influence the job of other proteins, and then as a result you get a particular cellular response that depends on the nutrients that are available for the cells. So, what we have found is that since these sirtuins, they are depending on the nutritional status of the cells, and we are studying how organisms respond to different availabilities of nutrients, then we thought that maybe these sirtuins are the links, the proteins that are acting as a link between the environmental conditions [00:27:00] and the response of the organs in the animal. So through the sirtuins, the animals know how to respond to different environmental conditions of nutrient availability. When the nutrients are scarce then the sirtuins are gonna feel that, and then they're going to tell the cells, hey, there are not that many nutrients, let's slow down our energy expenditure because we need to conserve energy and we don't know when the environment is gonna get better. When there are lots of nutrients available, then the sirtuins are telling the cells, Hey. There's plenty of nutrients and you can do the jobs that you are supposed to do. Another interesting thing that we found is that the sirtuins, they tell cells of different organs different things under the same environmental condition. So in conditions of high nutrient availability, the sirtuins that are in the cells of the liver, for example, they don't tell the same to the cells in the liver as the sirtuins that are in the kidneys, for example, or in the brain. And that's super interesting because [00:28:00] this means that under conditions of lots of resources, for example, so the body prioritizes the activity of some organs over others, right, presumably because these activities are going to produce a larger reproductive output in the long term, for example, or you're gonna leave more offspring, right, which is a measurement of success that biologists will use to know how successful an animal is basically by survival and reproductive output. So, that all these things combined led us to believe that, okay, so the hypothesis is that basically you have the different classes of sirtuins in different cells in different organs, right? And we think that fact alone can explain the patterns of resource allocation that you see in organisms, so for example, why organisms put less resources into reproduction when the quality of the food is very low. So our hypothesis is that these [00:29:00] conditions of low nutrient availability, the sirtuins are going to feel that in the reproductive system, the sirtuins are gonna feel that in the digestive system, the sirtuins are gonna feel that in different organs, and then there's sirtuins in the digestive system because the food is low quality, the animals need to eat more to get the same amount of nutrients. So the S in the digestive system are going to activate the digestive system. The digestive system is gonna be better processing food, extracting more nutrients. But you are using a lot of energy there, so you are not interested in putting as much energy into the reproductive system and the sirtuins in the reproductive system are going to tell the cells in the reproductive system to slow down. So under the same environmental condition, the sirtuins in different organs are gonna tell different kinds of cells, different things. And then the end result, what in the whole organism is a change in the pattern of resource allocation. How is that related to cancer? So [00:30:00] the relationship with cancer is that, if you think about it, cancer cells, there are cells that actually they are different from the cells in the body. So at some point, the cells in your body, they can experience mutations or something that makes them different. And what do they do? They proliferate, they grow, they proliferate, and their cell division rates are really high, right? There is a problem with this is that when you are a cell and you want to divide and divide, then you need a lot of energy. So basically the cancer cells, they produce molecules and they produce different things that tell the body to put resources into them, and basically, when you have cancer, you can die because of two different things: one thing is that the cells that were supposed to be, let's say liver cells, they're not liver cells anymore and they don't do what the liver does, and the second thing is that all the, you put lots of resources into these cells that are not doing really anything for the body, right? So the idea behind the use of sirtuins is [00:31:00] to basically use the sirtuin s to tell the cancer cells or to tell the cells in the body not to put resources into the tumor and to put resources into something else. So if actually the sirtuins are the proteins that are actually running the show, what we can do is to manipulate the expression of sirtuins in different parts in the body, so then we force, basically the body to adopt a different pattern of resource allocation, and we can tell the body where to put the resources and where not to put the resources. David Staley: And you've done this successfully? Agus Munoz-Garcia: We are now. So right now this is a hypothesis, and right now I'm collaborating with a Professor in the neuroscience department at Ohio State, his name is Karl Obrietan, and we are collaborating in a project in which we are going to basically force the expression of sirtuins in cancer cells and in normal [00:32:00] cells, and then we're gonna see what are the changes. And the hope is that if it works, we're gonna see a reduction in the proliferation and growth of the tumor cells. David Staley: Well, so my final question to you is how did you end up as a physiological ecologist? Of all the things in the world that you could have studied, classics, physics, how did you end up, how did you end up as a physiological ecologist? Agus Munoz-Garcia: The short answer is that I don't really know because since I was five, six, I don't even know, I was always interested in nature. I was fascinated by animals, plants, I was buying all these books about animals, for my birthday, my parents, instead of giving me, I don't know, toys or whatever, they will buy me plants or fish. I don't know. So it was weird. So I wanted to be a biologist even before I knew what biology . Then I had this friend that had a distant cousin that came to visit once and she was in [00:33:00] college and she was studying biology, so I talked to her a little bit and then I was telling her, oh, you study animals, so what are you doing? And she's doing, oh, my major is biology, and biology means this and that. And then I remember that I was seven or eight, and then I decided, okay, I wanna be a biologist, so this is what I like and I wanna become a biologist. And biology has many different branches, so then I did high school, I went to college, I graduated as a biologist, and then I came to do my PhD here in the US actually at Ohio State University. And the research project that actually caught my attention was about physiological ecology, I was doing this study in which I was comparing birds that live in extreme environments, in this case, it was deserts with the physiology of birds that were living in temperate environments. So actually Ohio and other places in Europe. And we were studying energy balance and water balance, and I [00:34:00] was really fascinated by that, and then that is what make me decide about my specialization. But actually it's very funny because when I was in college, I was a pretty good student, but do you know which is the course that I failed five times before I passed? David Staley: Physiological ecology. Agus Munoz-Garcia: Animal physiology. David Staley: Sure. Agus Munoz-Garcia: So it took me five attempts to pass the course. I had never believed that actually out of all the branches of biology, I was going to be a Professor in physiological ecology for whatever that's worth. David Staley: Well, Agus Munoz-Garcia, thank you. Agus Munoz-Garcia: Thank you very much for having me. Jen Farmer: Voices of Excellence is produced and recorded at The Ohio State University College of Arts and Sciences Marketing and Communications Studio. More information about the podcast and our guests can be found at go.osu.edu/voices. Voices of Excellence is produced by Doug Dangler. [00:35:00] I'm Jen Farmer.