By Bukre Coskun, Cell Biology, ‘18
“As a student in Professor Walter Leal’s biochemistry class, I was inspired by his dedication to motivating students and obvious enthusiasm for his field of research. Professor Walter Leal has achieved international recognition for his research on the molecular basis of insect communication and insect olfaction. Leal, a professor in the UC Davis Department of Molecular and Cellular Biology and former chair of the UC Davis Department of Entomology, has made significant strides towards understanding how chemicals deter mosquitos. He has identified key mosquito receptors that can guide the development of better mosquito repellents to prevent the spread of deadly diseases. He is a past president of the International Society of Chemical Ecology, an elected fellow of the American Association for the Advancement of Science (AAAS), and the first non-Japanese scientist to earn tenure in the Japan Ministry of Agriculture. I had a conversation with Professor Leal about his path to research, his philosophy on teaching, and the significance of his work with insects.”
BC: Did you have a moment where you thought, “This is the subject I want to study?”
WL: When I went to college, I was not sure what I wanted to do, to be honest. Initially, I wanted to do electronic engineering, which was a mistake! So, I changed my mind and did some chemical engineering. I got my first degree in chemical engineering, but did not enjoy my interaction with industry. For my PhD, I changed my route to pesticide chemistry and then to biochemistry. . . . It’s ok if you don’t know what you want to do, it’s very normal. Once you get in, you find out what it’s like. Some people look at a parent as a model, but most people don’t have much information about the field and if it’s what they want to do for the rest of their lives. So, they keep changing. I changed and I’m very happy that I changed.
BC:You invest a lot of time preparing videos and providing office hours for your biochemistry students. What’s your teaching philosophy?
WL: First of all, I want to motivate students. I try to sit in the place of the students. Whenever I prepare lectures, I think, “. . . If I was in the place of the students, would I be able to understand this explanation?” So, my philosophy is that I have to motivate the students and they have to continue the work by themselves. If they are not interested in the subject, they will just invest time to pass the exam. Motivation, I think, is the most important thing.
BC: Is that also why you do the Skype interviews with people from industry?
WL: Yes, because I think that the textbook can be boring since it doesn’t have much new information. So much happens in life in every aspect of science that we study. Skype interviews are a way to tell people, “You see, what I said here is not just textbook, it’s real life, it’s going on in the industry.” For example, we are going to study purification of proteins and the industry is doing this every single day. They are making new proteins for medicine and if you bring some of these examples to class, the students will realize this thing is not only for the exam. . . . That’s why I invited Renner Burkle from Genentech. His examples from the Vacaville plant were right on target.
BC: You do research with insects. Most people see insects as pests. What sparked your interest in them?
WL: I started with an emphasis on agricultural pests. When I studied pesticide chemistry…I started to use environmentally friendly strategies to control insects. In other words, I identified chemicals and pheromones that insects use in communication that can be a tool to interrupt that communication. When I moved to Davis, there was this West Nile Virus that came into California, so I thought I would. . . emphasize a bit more on insects of medical entomology, like mosquitos. There are a number of diseases mosquitoes carry. There is malaria, dengue, West Nile Virus and now Zika. I thought focusing on medical entomology would be very useful for society. . . . We have been working on repellants and attractants and many other things with mosquitos.
BC: You do research on the olfactory receptors of mosquitos. Can you talk a bit about the life cycle of mosquitos and how they utilize smell in this life cycle?
WL: The female needs blood to provide the nutrition for what will become the larva of mosquitoes. Mosquitos use a combination of many things to tune in on the host. They have senses for temperature, for humidity, for carbon dioxide and for chemicals that are coming out from our skin. The biology of mosquitoes is such that they are in the environment and they try to find a mate. . . . in mosquitos and most insects, the female keeps the sperm for later. In the case of mosquitos, she holds this sperm and goes to find the blood meal she needs to fertilize her eggs. Once the eggs have become very rich in nutrition, they come down from the oviduct into the water and are fertilized one by one with the sperm that she accumulated. It’s amazing biology!
The problem is that she might infect someone with a virus or pathogen that causes some disease when she goes for her blood meal. That’s not her “intention,” she just wants to try to get a meal. But let’s say that she bites you and you are infected with the Zika Virus. The female does not lay eggs only once, she has what we call multiple gonotrophic cycles. . . . She might mate a second time. She needs another blood meal, so if she had a virus that replicated in her body, she becomes the bridge in between people. That’s how you transmit a virus. . . . That leads to another type of research that we do with repellants. We want to find how these repellants work and what kinds of repellents we can make that are better for people to use. People don’t like some of the repellents because it smells bad and things like that. So, we are looking into this.
BC: With the study of repellants, what kind of behavioral assays do you do with the mosquitos?
WL: We don’t want people to put their hand inside of the cage. . . . we do some research with mosquitos that are infected so it would be immoral, at least unethical, to put someone there! Also, a human hand is not reproducible. One day we may attract mosquitos and one day we may not. That’s when the biochemical engineer in me came to help. I was able to develop a device that mimics the human hand and attracts mosquitos. . . . On one side we put this artificial hand and on the other side we put this artificial hand plus some chemicals that we know might be a repellant. Then we compare the response of the mosquito to one side or the other. This way, we can assess whether a certain chemical is a repellant and knock down receptors using technology that is available. . . .
BC: Do you collaborate with other labs?
WL: These days no one can do science on their own. I do all my work with infected mosquitoes in Brazil. . . . Last year, I went maybe four or five times for my research on the Zika Virus. I could get permission from UC Davis to get mosquitoes and infect them here, but it’s a more realistic situation when you have the virus that is circulating in the mosquitos in the moment. . . . In Davis, for example, I would get a virus from Puerto Rico or Africa and I would have mosquitos from Davis, but they’ve never seen each other! It’s not the real answer for the question. There are lots of surprises in science. We think, “Ah, that’s fine, we can use that mosquito from Davis and a virus from Africa,” but they have never seen each other. They probably won’t react the same way. So, collaboration is very important and we have to keep the doors open.
BC: You also have a study with moths and the pheromones they use in mating. It’s chemically very complicated. What are some challenges you face?
WL: It depends on the moth. We have done work on the receptor side but I have also done lots of research on identifying those compounds. Sometimes these compounds are very complex and the major challenge is that insects use very minute amounts. If the amounts were very large, any chemist would be able to identify those compounds. . . . we have to use some resources and techniques that allow us to guess those structures without seeing anything. Some well qualified scientists spend twenty years trying to find these compounds and they never do! In a couple of years, we were able to break down these structures. Sometimes persistence and luck is what you need.
BC: Speaking of structures of compounds, you found that the repellant DEET has a structure that is similar to a chemical that plants give off to defend themselves. How often do you see evolutionary connections like this?
WL: The question of DEET is not entirely resolved but. . . we found the exact receptor for DEET. DEET is not a natural compound, so we wanted to know why it repels mosquitos and the foundation for this. We made the connection that mosquitos also go to plants for a bit of nectar to have energy for flight. . . . We decided to take a look at the structures of a plant compound. We found that the receptors for DEET also respond to a compound plants use to repel enemies. But there is still a lot more to find out.
Questions of evolution are complicated because it’s all hypotheses and we test these hypotheses. A good way to find a solid answer is if we find different kinds of mosquitoes with the same pathway. All these mosquitos come from an ancestral species that separate at some point but we have a good answer for just one group. We don’t know if our findings are applicable to malaria mosquitoes, for example. So, we still have a little bit more work to do. The good thing about science is that the answer is never over. . . . We are never satisfied, there is never an end, there is always a little more. . . .
BC: Where do you hope you research will take you five years down the road. Where do you hope to be?
WL: My goodness, that’s a very difficult question! I have no idea what we are going to be doing five years from now. Every day in the lab we discover something new. If we discover something new and it takes us in a completely different direction, we are going to follow that direction. . . . For example, as we look at those receptors and we find something there that is maybe different in known biology, I want to go deep into that question.
BC: Who, scientists or otherwise, have inspired you in your life?
WL: There are so many people. A famous professor in chemical ecology at Cornell [Jerrold Meinwald] is one of the people that inspired me. He is 90 years old. . . I spent some time in his lab many years ago, he is a very inspirational person. There are lots of people but I don’t want to say names because I might forget someone. He is just one of the people whose line of thought I follow but we do completely different research now. He does more organic chemistry and I’m doing more molecular work.
If you ask me about a teacher, I would say that the person who influenced my teaching philosophy the most was my high school chemistry teacher [Aloisio Sotero]. . . . He was a very vibrant teacher and liked to motivate students and get everyone engaged. I probably got a lot of influence from that. My second year [of college], he quit his teaching job. Brazil didn’t have a lot science teachers so they got permission for high schools to hire university students. The high school hired me as his replacement. I was in college and I was teaching high school for a number of years. Maybe 75% or more of my Facebook friends are my high school students from when I was teaching them. I was very young and almost the same age as these students. . . .
BC: What is one piece of advice you would give to young researchers?
WL: Tomorrow I will have the Nobel laureate Jules Hoffmann answer exactly that question in class! Why don’t you take his advice from tomorrow’s lecture? He is one of the few people that got the Nobel prize for things related to insect in recent years.
Author’s Note: Jules Hoffmann advised us to find a good topic of research not yet covered by too many other people. He told us to work hard and remain connected with art and literature. He warned us that it’s not a good idea to dedicate your life to just one thing; variety is the key to success.
Editor’s Note: This conversation has been lightly edited for clarity and brevity.
Edited by Lauren Uchiyama & Lo Tuan