Season 4 - Episode 420
Mosquitoes are massive global agents of the spread of diseases like malaria and the West Nile virus. Cheolho Sim, associate professor of biology, has dedicated his research towards suppressing mosquito populations and slowing the spread of disease, recently earning a grant from the National Science Foundation to advance those efforts. In this Baylor Connections, Sim shares how genomic research into a mosquito’s circadian rhythm could be key to slowing the spread of disease, and examines how his lab lives out its motto, “driven by science, guided by compassion.”
Derek Smith:Hello and welcome to Baylor connections, a conversation series with the people shaping our future. Each week, we go in depth with Baylor leaders, professors, and more discussing important topics in higher education, research and student life. I'm Derek Smith and today we are talking about research from Baylor's department of biology. That takes a look at something we'll all be seeing this summer, and that is mosquitoes, but it goes way beyond that and we're going to learn about that from Dr. Cheolho Sim, associate professor of biology at Baylor. Dr. Sim's research focuses on vector-borne diseases and genomic studies that can help slow the spread of diseases like the west Nile virus into the suppression of mosquito populations. Dr. Sim leads Baylor's vector biology laboratory, whose motto is driven by science, guided by compassion that captures the spirit of research that can help people around the world from capturing these infectious diseases. A member of Baylor's tropical disease biology group, he is also part of a $532,000 plus NSF grant funding research into the roots of diapause. Which is the process by which mosquitoes prepare for the winter. And we're going to learn about that and more in the next 20 minutes or so with Dr. Cheolho Sim. Dr. Sim, thanks so much for joining us. It's great to have you here on Baylor connections today.
Cheolho Sim:Thanks Mr. Smith for having me.
Derek Smith:Yeah, that's really great to have you here and to learn more about research you've recently received this NSF grant, another piece of external funding for your work that we can dive into. And I want to start off by asking, I mentioned your lab slogan is driven by science, guided by compassion. When you think of the way you approach your work, you and your students in your lab, what does that phrase mean to you? Cheolho Sim: Yeah, in many cases, the researchers, scientists like me can be tracking on my own words in a small labs and immerse myself in my own research. So therefore, it is easy to get trapped in my own small worlds and forget the true meaning of research and life. Not only on the research, but I believe that the meaning of everything depends on how personally I grow through everyday work and how many people's lives get better by my work.
Derek Smith:Well, and we're going to find out more about that because obviously we're talking about tropical diseases. That's something that impacts billions of people around the world. And to zoom out from that a little bit, if you met a colleague from another department, maybe another department on campus and other discipline, and they ask you, what do you do? What's your research all about? How would you respond? Cheolho Sim: Yeah, the answer depends on who you talk to, but if you people is familiar with my research, like so-called expert, I say I'm studying the genetic control of mosquito factor, many infectious. If the other person is not an expert, I say the simply I research on mosquitoes in general.
Derek Smith:Mosquitoes and research in general. And if they said, well, what does that look like? If you told me it's mosquitoes and they said, well, what, what aspect, how do you research mosquitoes? What would you say? Cheolho Sim: Yeah. So mosquitoes on the venture goal is to control vector-borne disease, which is transmitted by mosquitoes. So including West Nile virus. And we know that Zika virus was a big issue a couple years ago. And also the most notorious one is a malaria, malaria can cause more than half million deaths per year. So the best way is to control vector-borne disease is a historic police, suppress and control mosquito population.
Derek Smith:Visiting with Dr. Cheolho Sim and Dr. Sim, when did you first become interested in mosquitoes and vector-borne diseases? Where did that spark for you? Cheolho Sim: Yeah, it started from humble beginnings. My hobby is actually collecting insects. It was, has been my hobby since I was a very young child. I love to go out in the field, collect butterflies and looking for flowers, other insects. There was, it was my hobby when I was very young and eventually there was a lead to decide my major in biology and entomology in college. So I finished my undergraduate and master's degree in biology and entomology major. When I was in, I was born in South Korea. Then I decided to join Dr. Frank Colin's lab at University of Notre Dame. And he was a leading expert in mosquito genome studies. And also he was a director of center for tropical disease and research at University of Notre Dame. I did my doctoral degree and it was like a yesterday. It was 20 years ago and this research center, center for tropical disease and training. They completed many of the mosquito genome, which is a DNA map. The mosquitoes, including Malaria Mosquito, Anopheles Gambiae, Dengue Virus, Vector Mosquito, Aedes Aegypti and my mosquito, west Nile virus back the mosquito Culex pipiens and many other mosquito genome. So this is where my research began, start with the interest in mosquito genomics and the infectious disease transmitted by mosquitoes.
Derek Smith:So from Notre Dame, what, what brought you to Baylor? How did you join the Baylor faculty? Cause it seems like when you talk about being guided by compassion and helping people, that's something that's a great fit here at Baylor. Cheolho Sim: Baylor has a long history, the many of the former professors working on vector-borne disease. So there is a tradition, you know, Baylor and really good setting in terms of research lab. And so there was a time when I found this is a good place to study vector-borne disease.
Derek Smith:Visiting with Dr. Cheolho Sim associate professor of biology at Baylor. And and you mentioned that the role malaria can play in deaths around the world a moment ago, but I want to ask you most of us know mosquitoes spread disease, but maybe for those of us, you know, many of us don't understand the full impact. When you think as a scientist, when you think of the role that mosquitoes play in the spread of disease around the world, are there numbers or images? What, what comes to mind? Cheolho Sim: Yeah, that's a good question because of COVID epidemic, many people have become aware of more of the importance of infectious disease research now. And in addition, mosquito can transmit many infectious agents, such as viruses, including west Nile virus, Zika virus, and also infectious bacteria and infectious nematodes, which is called Wuchereria Bancrofti, Brugia Malayi. And these are parasite is infectious. And also most notorious one is a malaria parasite, which is plasmodium species. And Malaria alone can cause more than half a million deaths every year. So this is a very big issue. And these vector-borne disease are transmitted in mostly less developed countries and tropics and subtropics regions where mosquito grows well higher. However, due to continued climate changes, we know very well in Texas. The disease is spreading more and more new regions and other countries also, including the United States.
Derek Smith:Dr. Sim, what are some of the questions with that now, as you've described the, the problem and the challenge, what are some of the questions that you're specifically driven to answer the drive, you and you go into work in the morning. Cheolho Sim: Yeah, as I mentioned earlier, that controlling effective mosquito population, which we can stop factor one disease, including Malaria, West Nile, Zika virus, and has been the most successful way is to control vector-borne disease so far. So it was to use a chemical such as a pesticide. This is the most effective way so far. However, in this chemical method, the mosquito population evolves into a resistance mechanism against the pesticide. Which is usually average, it takes about every two years, it's getting very fast. So eventually chemicals, including pesticides cannot be used to control mosquito populations. So in our laboratory, we conduct first the basic research about mosquito development process, such as the diapause and the other one is a sex determination processing the mosquitoes. As these research, basic research accumulating, then we eventually seek to find a way to control mosquito population, not by chemical approach through biological or genetic approaches. That's the main goal in the lab.
Derek Smith:I know I spoke to you, it's been a few weeks ago now about your, NSF grant. And it's fascinating to think about, you know, like you said, if they can keep a couple of steps ahead of the chemicals every couple of years, they've got to find a way to get out in front of them. And that's what you're working to do. So let's dive into these different ways that you just described, whether sex determination or diapause, let's start with, with diapause, because I know that's a, a big part of the NSF grant that, that you've received. Tell us a little bit about that and what the NSF grant, what kind of research this is funding. Cheolho Sim: Yeah. So you showed an NSF research grant focusing on basic science studies. In my case, I'm answering the question of which genes play an important role in mosquito dipoles. So to answer that question, I use the, one of the modern mosquito Culex Pipiens. It is also the main mosquito vectors transmitting west Nile virus in the United States. So that is a main, the question that I try to answer through these NSF research grant.
Derek Smith:Well, let's what is diapause exactly? What, what is diapause and what role does it play in the life cycle of a mosquito? Cheolho Sim: Yes, mosquito diapause is a similar to how polar bear hibernate to get through the winter seasons. So in diapause mosquito in a field, usually their lifespan is around about a month. But when they started this diapause Geri program, they can survive a five or six months. So this diapause is extending their lifespan by five, six, times more to solve so that they can survive through the over winter. And the diapause in mosquito begin to store two or three times more body fat. It start from late summer and also in the fall. So use that body fat in the winter because they cannot find the food into winter season. In addition, it increase resistance to low temperature. So increase the stress tolerance, you know, cold temperature. And the most important thing is there is a mechanism to suppress virus replication during diapause time. So nothing's containing known about the mechanism, how this mosquito inhibiting virus replication, including west Nile virus in other vitals. So that's a spring, they carry over this virus when they stop diapause in a spring, the virus replicating again. So, you know, springtime, they can transmit it or gain those virus. So does the identifying find out which gene plays on important role in each of these diapause trait, can lead us to new approach or new insight controlling mosquito populations in a winter system. Which is the most vulnerable time in terms of mosquito population growth.
Derek Smith:So we've all Dr. Sim, probably misjudged the weather at some point and Ben needed a jacket, but we had short sleeves on an outdoor event. So what you're basically trying to do is is that on some level, mosquitoes are getting fat and warm and happy for the winter. And you're trying to find out where that gene is to shut that off. So they don't do that. And all of a sudden, Cheolho Sim: Yeah, they cannot survive.
Derek Smith:yeah, they're, they're left, they're left exposed. So if you, know this process happens, but it's complex mysterious Dr. Sim, where do you begin looking for the roots of this? Cheolho Sim: Yeah. The previously many scientists shows them mosquitoes perception of environmental cue is from summer to winter is a change in the day, a nice cycle, which is called photo period. So see glaring that the photo period that decreases the mosquito begin to prepare for winter through a number of different feature, logical changes such as, as I mentioned, increase the body fat stress polos, extended lifespan, suppressed by replication. In addition, the molecular mechanism for lack colonizing the change in the photo period, which is, you know, from the summer to fall to winter season, they, they lie cycle getting shorter and shorter and shorter. So somehow they understand mosquito is very interested in how these mosquito understand that they like change. Right? So this changing of photo period is very well known, which is called polar clock clock system, or called a circadian clock system. So the, in this grant, we proposed these circadian clock genes, you know, blue collar crack system is actually initiating mosquito tire post program. So there's one of the key and key questions. We try to answer which teaching actually controlling diapause program.
Derek Smith:We are visiting with Dr. Cheolho Sim, associate professor of biology here at Baylor. And so, you know, that's a phrase most of us have heard in our own lives. When we think about our circadian rhythm, you know, sometimes if we're not getting enough sleep or staying up too late, people will talk about that. So when we talk about these clock genes that impact this, they can have a 24 hour cycle impact, but maybe even a much larger impact than that, but the seasonal impact. Cheolho Sim: Yeah. So that is still a mystery. We tried. This hypothesis is, has been in a science group more than 50 years. So ladies scientists propose that circadian clock, not only daily life, daily changing the wake and sleep cycle, but also it can has an impact on seasonal change. As we know, many human disease has a seasonal change. There are more depression in a winter season, something like those kind of a seasonal change, but it wasn't quite, we don't have any clear answer for, is there any clear, tangible link from the circadian clock system to the seasonal chain? So we are focusing on basic science in mosquito, but impact B show the link from daily life, daily cycle, change the clock genes somehow how they link to the seasonal change, which is we have no clue between these huge puzzles there. So we hope they try to find out that some basic science.
Derek Smith:You talked about, you know, genomic studies, as it relates to mosquitoes and sequencing. You talk about the puzzle there. What tools in genomic studies allow you to kind of search for the pieces of the puzzle that fit together. If we were to peek over your shoulder, as you and your colleagues and students were conducting this research, what might we see you? Cheolho Sim: Yeah. So the basic question we are focusing right now is a food genes in a circadian clock system, which is the gene name is very interesting gene name, which is timeless period. PVP one is cycling, which is transcription factors. So we try to understand that, you know, to legislate the expression and inhibition of these core clap genes, we need a gene genome, which is a DNA map, which will provide will each region located in the mosquito chromosome. Since the genetic information of culex pipiens mosquitoes was already the Code to 10 years ago. So we can get the information, what we want through genome database, which is called vector base. So it's a more like if you want to get to your dollars in a certain, the more you use a Google map. So you get to the point where you want to go. And which is a very similar way that you can have new genetic information using this genome database, which is we use recorded vector-based is more like using Google maps.
Derek Smith:Visit with Dr. Cheolho Sim from Baylor biology. And I think that's such a mysterious process to most of us. You know, you describe it so well, it's like Google maps, but what are some of the things you look for as you study the map? Are there things that when you see them, makes your antenna go up, but makes your pulse quick and a little bit, what are some of the things you keep an eye out for as you look through this very, very big map. Cheolho Sim: Yeah. So actively find out these location of each gene. Each gene has a unique structure. We call the Exxon and interferon and five-prime UTR. The priorities is a little bit of complex structures. Now we have a new tool. It's like we call the genetic Caesar. So you can precisely caught an insert, a certain DNA in the, those, your target gene. So this is called CRISPR CAS nine system. So you're caught in a certain part of the DNA sequence so that they, it cannot produce a certain, their target, you know, at PDP proteins. So then means we call it a disease, a gene laptop. So you suppress certain gene, your target genes, so that you want to find out what their functions are. If there's no in activities gene then means they cannot perform their expression. So they might lose the daily cycle or weight and sleep cycle, which might lead to the stopping diapause phenotypes. So this, we are trying to use that CRISPR, personalized genetic Caesar. The other technology right now is that when we have a human genome, one human genome cost more than close to the more than $2 billion, but now we have next generation sequencing technologies. So if you want to have a, your own gene, it costs $1,000. See that last 20 years, the technology is revolutionized the whole field. So this next generation sequencing and allow us to look at the whole genome, not in a one gene hold, you know, what change happens. So do using those next generation sequencing technology, we can actually find out aging how they control other genes. So those are the two things that we use in the lab.
Derek Smith:That's great. Well, Dr. Sim, as we head into the final couple minutes, I want to ask, you know, your research, you know, you mentioned that some of these theories have been around, you know, for 20 or 50 years, but technology is advancing so rapidly that it changes your ability to determine things. I know you're kind of in, this is a long game that you're playing, right? This is a long haul haul kind of game. How should we view the timeline now on this and the work that you and people, you know, who do similar work are doing as you fight vector borne diseases and tropical diseases. Cheolho Sim: Yes. To answer the complex issue, it takes a long time. So yeah, this surgeon was still diapause, and we'll have a clap has now just started. So next 10 years, we, our lab is, will focus on foundational research, which teaching control these types of phenotype diapause. And after that, we hope that we can apply this new knowledge, apply this in the, as I mentioned before on biological tools and genetic tool. So we're back here and sets way should change a scheme. We hope to apply this technology to endemic regions. So, vector won't disappear in next ten years.
Derek Smith:That's great. Well, we'll look forward to seeing, you know, as you work on this NSF grant in the years ahead, what comes of that. And continuing to follow along and says you fight tropical diseases with your colleagues around the world. For sure. Well, Dr. Sam, thank you so much for taking the time to take something complex and break it down for us so we can understand and share in the work you do. I really appreciate it. Cheolho Sim: Thank you. Thank you for having me,
Derek Smith:Dr. Cheolho Sim, associate professor of biology at Baylor, our guest today here on Baylor connections. I'm Derek Smith arrived reminder. You can hear this end of the programs online, baylor.edu/connections. Thanks for joining us here on the Baylor Connections.