Flaminia Catteruccia

Spectrum

Flaminia Catteruccia discusses the molecular basis of mating and reproduction in Anopheles gambiae mosquito. Her research provides insight into the mosquito reproductive biology to better develop vector control. Catteruccia is Associate Professor of Immunology and Infectious Diseases at the Harvard School of Public Health.

Transcript

Speaker 1: Spectrum's next.

Speaker 2: [inaudible] [inaudible] [inaudible] [inaudible]

Speaker 3: [inaudible].

Speaker 2: [inaudible].

Speaker 1: [00:00:30] Welcome to spectrum the science and technology show on k a l x Berkeley, a biweekly 30 minute program bringing you interviews, featuring bay area scientists and technologists as well as a calendar of local events and news.

Speaker 4: Good afternoon. My name is Brad swift and I'm the host of today's show. Our interview is with Dr Flaminia cutthroat Chia associate professor of immunology and infectious [00:01:00] diseases in the department of the same name at the Harvard School of Public Health. She is also an associate professor at the University of [inaudible] in Italy. Malaria is a leading cause of death in tropical and subtropical regions. The plasmodium parasite that causes malaria is transmitted by the biting of female [inaudible] mosquitoes. Dr Cutthroat Chias group studies the molecular basis of mating and reproduction in both the female and male of [00:01:30] four species of mosquito. They are looking for the most effective and robust strategies to frustrate mosquito reproduction. Overall, they aim to provide insight into the reproductive biology of this malaria vector, which until recently remained largely unstudied. So the new targets for vector control can be developed. And Dr Cutolo Chia was in the bay area recently for a conference and I was able to arrange an interview Flaminia Katja, welcome to spectrum. [00:02:00] Thank you. What'd you give us an overview of your current

Speaker 3: object? Yes, sure. So my research group is based at the Harvard School of Public Health, uh, is working on, uh, the biology of the mosquitoes that transmit malaria in Africa. And mother is still a massive problem for tropical and subtropical countries, but in particular for Africa as it scales almost a million people every year and infects not 200 million people [00:02:30] every year. So it's a massive social and economical problem and malaria is transmitted by mosquitoes. So we believe that if we can stop mosquitoes from transmitting malaria, then we can solve a big problem for the countries that are affected. Three particular, my group focuses on studying some aspects of the mosquito biology that are important for malaria transmission and will focus on reproduction on how mosquitoes reproduce, what makes them fertile. Because [00:03:00] at the end of the day, our goal is to develop novel methods to control mosquito populations. And we think that we could control them by introducing sturdy to international populations as an alternative to what's already been done now, which is mainly based on the use of insecticides to kill them.

Speaker 3: And, but they have to be quite targeted ways to use the insecticides by pushing these insecticides on mosquito nets. So that mosquitoes that try to bite on night while people are asleep and the nets get killed [00:03:30] or through sprays or insecticides inside and house walls to kill mosquitoes at arresting indoors. But these methods are not sufficient to stop moderate transmission. And also mosquitoes are becoming resistant to the action of insecticides, which means they're not killed anymore and they change their behavior rather than biting at night inside houses to start by the outdoor and during the day so that insecticides can not get to them anymore. So our thought is our instead is on the idea that, uh, rather than killing [00:04:00] mosquitoes, we can sterilize them so that then there'll be fewer mosquitoes out there. They can transmit malaria and then eventually malaria transmission will stop.

Speaker 3: And so we study how mosquitoes reproduce, what's important for their reproductive biology. And we have three major avenues or research. The first one is we try to understand what's important for reproduction because one tracking aspects of reproduction in the malaria mosquitoes is that the females have sex only once in their lives and after that they [00:04:30] completely switch off. They're not interested in more. And so this is quite a vulnerable step in the life cycle of our mosquito because it happens on once. So we are very much interested in understanding what is it that happens to females, what's the switch that completely abolishes that their receptivity to compilation. Because in principle, if we could understand what are the refactoring is as a call to further copulation, then we could induce the same mechanisms in variant females [00:05:00] and trick them into thinking that they've made it. And so they would make any model contributed to the next generations.

Speaker 3: So that's a big area of our research where we try to understand what happens to females after copulation after sex so that we can identify what are those factors that change that behavior so that we can induce them. The second area or research and studies is a more translational side. We are interested in developing tools to induce the reality [00:05:30] in male mosquitoes. One idea of control is based on the release of males that are sterile. This males will of course try to find females to have sex with them and eventually those fund them. But there'd be no project coming out of these compilations. And so if we keep doing this over and over again, if you keep releasing sterile males, then we can sterilize most of the females that are natural populations and so the population will crush. And so with malaria [00:06:00] transmission, and so we are trying to find ways to serialize males in a genetic way, introduce genetic stability rather than using irrigations or chemo sterilizations as it's done for other insects.

Speaker 3: Because it's important that whatever we do to fertility, it doesn't affect biology. The general biology of this mosquitoes and their behavior and also their fitness and that of competitiveness in terms of meeting and normally irritation or chemo sterilizations, those [00:06:30] can cause severe fitness costs to these mosquitoes. And so we got a little more subtle than we tried to study. So the mosquito DNA and understand what are the factors that are important for my facility so that we can interfere specifically with those factors. And so develop a male mosquito that is sterile and then we can release in the field. So that's our second area of research. And then a newer area research that we're interested in is in understanding what's the impact of what we do in terms of malaria transmission in particular, in terms [00:07:00] of what would be the impact of these measures on the ability of the female to transmit malaria.

Speaker 3: Because if we introduce sterility in a population, how does that effect the partial development within those females? We don't want to develop mosquitoes that are sterile, but at the same time that are better at transmitting malaria. And so one new aspect of our research is trying to understand what's the link between reproduction and mosquitoes and Parkside development inside the female. So this [00:07:30] is broadly what our love is doing. Why is it that malaria is so lethal? Well, the mother has been eradicated from large parts of the world, has been eradicated from the u s from Europe and we are actually quite close already getting malaria in Africa as well in the fifties and sixties with the use of insecticides use a queening. And so drugs to kill the precise insecticides to kill mosquitoes. But unfortunately [00:08:00] those programs were stopped because of a number of reasons. And within a few years the number of Americans really went back to what it was before these programs were even started.

Speaker 3: So one of the problems with malaria said it's a very dynamic disease from one single case, you can have tens and hundreds of secondary cases that can spread very quickly. So it's very difficult to control. So the synergy between the mosquito and the malaria [00:08:30] is the enabling factor in principle is a preventable and curable disease. It shouldn't be so deadly. However, our ability to control it in the countries where it's presence at the moment is limited by logistic reasons, lack of hospitals, lack of resources, and the fact that the mosquitoes are very efficient at transmitting the parasite. [inaudible]

Speaker 4: [00:09:00] you were listening to spectrum on KALX Berkeley. Our guest today is Flaminia Qatari Chia molecular entomologist at the Harvard School of Public Health, researching mosquito reproduction as a way to combat malaria. How long has your project been going? We've been working on it for six [00:09:30] years. So that's kind of new. Yeah. And does it have a length of time or is it pretty open ended?

Speaker 3: It's open-ended until I get funded. It's the funding. Yes, yes. Always is, isn't it? Yes. And of course, until it's relevant release, I think the funding will be there until this was a breakthrough. Yeah. A solution. Yes. Yeah. Yeah. And Udall, was that a completely empty niche? No one was doing that. So we are really the first ones looking at reproductive biology in this mosquitoes from a molecular [00:10:00] and genetic point of view. Most of the studies before us were performed at the ecological level. So there's actually quite a lot knowing about the ecology of reproduction, but not much known about genetic factors and the pathways that are important for fertility. That's something that is completely new. So whatever we find is novel. So it's exciting for us, but at the same time, we have to do everything you know, is, we have to start from scratch. So it's more challenging maybe

Speaker 4: once [00:10:30] the mosquito has ingested the parasite, the malaria parasite from a human, how does it interact with the mosquito?

Speaker 5: Okay.

Speaker 3: The parasite has a complex life cycle inside the mosquito vector, and it takes a few days to complete from when the mosquito ingests the parasite. When the mosquito can inject the parasite into the next person, it takes about 12 days. And that's the time that the press site needs to go through different developmental stages. [00:11:00] And so once some mosquito takes sliders infected, then the process will have to leave the blood environments. There'll be a stage that happens inside the mosquito midgut and then the prosight will have to leave as quick as possible. Uh, the makeup before he, it gets killed by the mosquito enzymes, digestive enzymes particular, and then it'll have to find its way to the salivary glands, which are these tissues where saliva is produced by the mosquito. And once it reaches the Salami Glands, then [00:11:30] it can be injected into the next person because during blood feeding, the female will inject a little bit of saliva into the team of the person that is this biting.

Speaker 3: And so during that process the process can be transmitted. Actually most mosquitoes don't even live long enough for the proceeds to develop. So that's a major roadblock or process in development. Is there any thought to trying to alter the parasite itself? There's a lot of research on modifying [00:12:00] the mosquito so that rather than allowing person development, they'll kill the parasite. And of course there's a lot of research on finding drugs that can kill across sites in people that are infected. And there is research on malaria vaccines as well. We don't have a vaccine yet. There is a vaccine that is now in Stage three trials that could be promising in combination with other control measures. It's quite clear that malaria will not be defeated by using a single measure. So [00:12:30] the use of insecticides, possibly the use of sterile males, hopefully combined with the use of drugs to confirm [inaudible] in people and hopefully also without, without vaccine that could be effective for awhile. We will need all these measures to control the spread of the disease.

Speaker 4: How large your group is, is the group that's working on your project.

Speaker 5: Okay.

Speaker 3: My group is composed by about 10 people at the moment.

Speaker 4: And what are the different scientific disciplines you've brought together [00:13:00] with that group?

Speaker 5: Yeah,

Speaker 3: well it's a combination of molecular biology and genetics and biochemistry. Also evolutionary biology, big of ecology as well.

Speaker 5: Okay,

Speaker 4: and within the group, how do you orchestrate the workflow of all that? How do you decide which thing you're going to focus on at what point in time

Speaker 3: to go ahead and go forward with the research? Oh yeah, those are actually tough decisions sometimes because there is so much [00:13:30] that we can be doing, just so many different ideas. It's circulated in the lab and sometimes it's difficult to prioritize them. So in general, we do discuss ideas all together. I can come up with some ideas and then we discuss, uh, with the group and some we like the brainstorming and then more ideas emerge. And then we focus on what's more important according to our priorities. We always have to make choices. We tried to have projects that are most solid in a way that we [00:14:00] know will give us results quite quickly. And then at the same time also establish longer term projects for maybe bigger goals. So it's a combination of all the two.

Speaker 4: What is the life cycle of this mosquito?

Speaker 3: So the mosquitoes we work on, um, anopheles mosquitoes that, that are not fillings are the only mosquito, second trust mates, uh, malaria to humans and draw about 30, 40 and awful in species that transmit malaria. And we study in particular, um, our mosquitoes called [00:14:30] Anopheles Gambiae and that's the most important vector in Africa and therefore the most important actor in the world. But we also start in some other mosquitoes out important vectors in other parts of the world. We are now interested in southern American vectors, Asian vectors. So we have four different mosquito species in our lab for comparative studies and Life Cycle is from a female that is, I've been intimidated by a male. Then this female will need to feed them blog to develop eggs. And that's the step that is exploited [00:15:00] by the plasmodium parasite of malaria to be transmitted. And so the female will feed on blood preferentially on, on men, on humans.

Speaker 3: She will develop her eggs and then the eggs will be fertilized by the sperm that is transferred from the male. The eggs will be laid water, so the eggs will hatch and give larvae. And then a pupa will with form that doesn't feed. And then after two days and adult will emerge from the PUPA. And so our, as a, as that [00:15:30] little step, males and females will have to find each other for copulation and then the female will have to block feed again. And so that the cycle can start all over again. So overall from egg to egg is about a couple of weeks. The Life Cycle

Speaker 2: [inaudible]

Speaker 6: this is k a l x Berkeley. The show is spectrum. Our guest is Flaminia [00:16:00] [inaudible]. She's working to eradicate malaria.

Speaker 2: [inaudible].

Speaker 3: Is there a side effect to affecting the mosquito population so thoroughly? Yeah, that's a very good question. What are the possible effect on the ecosystem of mosquitoes? Useful for anything? Do we need mosquitoes in this world? And these are very good concerns, very reasonable concerns. [00:16:30] However, the Fallon sets targeting fertility is a very specious Pacific control measure. Unlike the use of insecticides where you kill everything that comes in contact with insecticide, if you use mosquitoes to eradicate mosquitoes, that's a very selective way to do that. It's a very specific way to do that. So I think that the effects on the ecosystem will be very marginal, but of course that's something that will have to be followed and would have to be monitored, will be a very insane eco-friendly way to reduce monitor transmission because you would, [00:17:00] we would only target those pieces that cosmic me [inaudible] thousands of mosquitoes species on the planet and only 20 or 30 I at transmitting malaria so we wouldn't kill all mosquitoes and we would only have to target those that ugly at transmitting the disease.

Speaker 3: With the mosquitoes that you're growing in the lab, how are you feeding them? We feed them differently depending on their developmental stage, so we, the larval stages, the early stages, we feed them with fish food or cat food and for the adults [00:17:30] we feed them with sugar solutions that both the male and the female will feed on. So it's water mixed with sugar and then the females, we have to feed them on bloods for egg developments, we feed them with blood that we buy from blood banks. So we've completely eliminated the use of animals for that, which is we are very pleased with.

Speaker 4: Do you feel you're close with the sterilized male part of the project and do you have plans to try to take it to the next level?

Speaker 3: Yeah, we, we are thinking [00:18:00] a lot now about how we can make our system more effective because the way we in use steroids in this males, it's very inefficient in the lab. We need more than a day's work to get 20 or 30 males that are sterile to how do we scale this up. We really need to push and hopefully we can work with engineers and find the best way to scale this up and do the automated way that can be much more effective.

Speaker 4: [00:18:30] You're continuing to pursue the female side of it.

Speaker 3: The female side of it is what's more exciting for us in a way because there's more biology behind it, but we're also very much interested in understanding what are the determinants of fitness in the males because when we make them sterile, we'll still need to make sure that there will be competitive for meetings with feel females. And so apart from studying the biology of reproduction in females, we're also very much interested in that in what makes a meal good [00:19:00] meal, a fit meal that will have good chance of success once it's released. So yeah, that's why we are studying both male and female reproductive biology. We are not just selling waist to induce 30 but also what are the determinants of fertility?

Speaker 4: If you succeed in creating a sterilized male or a female that doesn't lay eggs, do you have a plan or is there a plan for how to introduce them into the wild [00:19:30] or is that something that would need to be developed when the time comes?

Speaker 3: We don't have a plan as such, but we are starting to think about a plan in terms of the logistics of it. There is a lot of know how that comes from the release of sterile males for targeting other insects, species, insects, pieces that are mainly agricultural pests like fruit flies, Milo flies, school worms, potato. We will do that. Old insects that cause the via damage [00:20:00] to the agriculture. It's a drug programs and based on the release of millions of sterile flies all over the world really. And so all the issues concerning the mass production of these insects, the packaging and the distribution of these stallions, six to the places where they're needed and then the release, all those issues have already been sorted out for other insects and so in principle shouldn't be too difficult to transfer that expertise onto mosquito work. It [00:20:30] should be feasible. We don't have the expertise in ourselves, but working in collaboration with the people that have it, that should be possible. I'm optimistic that that could be done without huge efforts.

Speaker 4: Are you teaching as well as doing your research?

Speaker 3: Yeah, I have some teaching to do is not massive. I mainly teach postgraduate students and I teach while they work on, so it's infectious diseases. My teaching load is not very big. Maybe it will get bigger in the next few years because [00:21:00] I've just started a year ago and I'm enjoying it. I enjoy teaching postgraduate students very much because they're small groups and normally they're very interested, very dedicated and also they ask amazing questions. So it's actually quite fulfilling. I know that some of the Harvard students are just brilliant, so it's a different experience from what was used before. I like it very much. Yeah. But I really prefer doing research. You know, it's, it's like that's my first, uh, my [00:21:30] top priority is to do good research, but of course we have a mission to encourage the next generations to get into science and getting into research. I like the idea of contributing to that. Flaminia Katya, thank you very much for coming on spectrum. Welcome. Good luck. Thank you.

Speaker 7: I'm gonna [inaudible]

Speaker 3: um,

Speaker 6: if you would like to hear a previous [00:22:00] spectrum show, they are archived on iTunes university, go to the calyx website, calix.berkeley.edu. Click on programming, select news, scroll down to spectrum and that section. There's a link to podcasts or send us an [e-mail] and I'll send you the link.

Speaker 2: [inaudible]

Speaker 8: [00:22:30] a feature of spectrum is to present news stories we find interesting. When the news are Renee Rao and Rick Karnofsky,

Speaker 9: the UC Berkeley habitus will play host to the first ever dreambox a three d printing bending machine. By the end of this month, the machine will allow users to take advantage of three d printing technology without paying steep up front costs for the machinery [00:23:00] to use. The machine users will first choose an item model within Dream Boxes Catalog upload one of their own via the web. Next, the print command is given and the order is sent to a cloud based print queue before being directed to the vending machine. Once the item has been created, it is put into a locker with a unique unlock code that is texted to the users. The creators estimate that each use of the printer will range from two to $15 on average depending on the complexity of the object and the materials used.

Speaker 8: [00:23:30] A team from New Castle University reported in science that honeybees are three times more likely to remember a learn floral scent when they are rewarded with caffeine. Caffeine occurs in coffea and citrus species and to be pharmacologically

Speaker 9: active but not repellent to the bees in higher concentrations. It is known to be toxic and repellent due in part to the bitter taste, but in lower concentrations that occur in nature. It offers a reward. [00:24:00] The team also applied caffeine to the brains of the insects and observed that it increased activity aiding the formation of longterm memories.

Speaker 2: [inaudible].

Speaker 9: A [00:24:30] regular feature of spectrum is dimension. A few of the science and technology events happening locally over the next few weeks. Rick and Renee present the calendar this March nerd night. East Bay will feature UCB associate Professor Matt Walker on Sleeping Memory Guy Branum on the invasion of Canada and the Chabot space and science centers. Jonathan Bradman on the night sky. This will happen Monday, March 25th at the new Parkway Theater in Oakland. Doors will open at seven show begins at eight. [00:25:00] Tickets are available online for $8 and all ages are welcome. Past spectrum guests, Michael Isen will be speaking to the Commonwealth club on the subject of reinventing scientific communication. While most scientific literature is now online, it remains as inaccessible to the public as it was centuries ago. With the physical limitations of print journals replaced by expensive publisher paywalls, [inaudible] who cofounded the Public Library of science. [00:25:30] We'll discuss the scientific journals and new open access models. Tickets are $20 or $7 for students with valid id.

Speaker 9: The talk is on Wednesday, March 27th in San Francisco. There is a [e-mail] for tickets and more info this April 2nd the ASCA scientist lecture series. We'll discuss tiny creatures with the ability to invade your body, [00:26:00] hijack your cells, change your DNA, and modify you physically and behaviorally to suit their own devious goals. Jack Mackarel, director of the Center for discovery and innovation in parasitic diseases will lead the talk on the parasitic organisms that live among and inside us. Some of the world's most pernicious diseases are caused by these supreme sophisticated organisms, but according to evolutionary biologist, parasites have also played a significant role in shaping the human species. The event will be held Tuesday, April 2nd [00:26:30] at 7:00 PM in Soma Street food park near the corner of 11th and Harrison. Leonardo art science evening rendezvous or laser has several talks this month.

Speaker 8: Jess holding explains the use of light and other natural phenomenon to explore perception. NASA is Chris McKay will speak about the curiosity. Mars mission, USF Vagina and Nagarajan presents embedded mathematics in women's ritual [00:27:00] art designs in southern India. She'll talk about the geometry of rice powder paintings. Finally, Nikki, you Layla will discuss the mechanics and construction of marionettes. Laser takes place@stanforduniversityonaprilfourthfromsevenpmtoninepmmoreinformationaboutthelaserseriescanbefoundonthewebatleonardo.info.

Speaker 9: That's pretty good. Tuesday, April 16th in the Tuscher African Hall, Mary Roach [00:27:30] will lead an unforgettable tour of the human insides. Questions inspired by our insides are taboo in their own ways. Why is crunchy food so appealing? Why doesn't the stomach digest itself? How much can you eat before your stomach burst? Can Constipation kill you? Did it kill Elvis? Roche will introduce her audience to the scientist who tackle these questions. She will then take the audience through her experiences in a pet food taste test, lab of bacterial [00:28:00] transplant and alive stomach. This lecture will take place Tuesday, April 16th at 7:00 PM in San Francisco for more information and to get tickets in advance, go online to cal academy.org

Speaker 2: [inaudible] [inaudible] [00:28:30] music card during the show is by Lasonna David from his album folk and acoustic made available by a creative Commons license 3.0 attribution. Special thanks [00:29:00] to David Dropkin for helping set up the interview. [inaudible] thank you for listening to spectrum. If you have comments about the show, please send them to us via our email address is spectrum dot [e-mail] join us in two [00:29:30] weeks at this same time. The [inaudible] [inaudible] [inaudible].

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