Naoki Yamanaka, an assistant professor at UC Riverside (UCR), is known for his innovative and creative research. In fact, the National Institute of Health (NIH) just awarded him a $2.4 million grant in its High-Risk, High-Reward Research Program to study the role of steroid hormone transporters in insect development and reproduction. A UCR news release pointed out that he will "translate that knowledge into new ways to combat the spread of mosquitoes, which are among the deadliest animals on the plant."
Fast forward to today--actually next week! And this time, it's about fruit flies. Steroid hormone transporters in fruit flies.
Yamanaka will discuss "A Membrane Transporter Is Required for Steroid Hormone Intake in Drosophila" at the UC Davis Department of Entomology and Nematology seminar, set from 4:10 to 5 p.m., Wednesday, Oct. 24, in 122 Briggs Hall. Host is seminar coordinator and medical entomologist Geoffrey Attardo, assistant professor of entomology.
"Steroid hormones are a group of lipophilic hormones that are believed to enter cells by simple diffusion to regulate diverse physiological processes through intracellular nuclear receptors," Yamanaka explains. "We recently challenged this model in the fruit fly Drosophila melanogaster by demonstrating that a membrane transporter that we named Ecdysone importer (Ecl) is involved in cellular uptake of the steroid hormone ecdysone.Eci encodes an organic anion transporting polypeptide of the evolutionary conserved solute carrier organic anion superfamily. Results of our study may have wide implications for basic and medical aspects of steroid hormone research."
Yamanaka, who received his doctorate in biological sciences in 2007 from the University of Tokyo, says that his lab is "focused on identifying and characterizing neuroendocrine signaling pathways that regulate physiological and behavioral changes during insect development. Similar to humans, where physical and mental development during juvenile stage (puberty) is controlled by the neuroendocrine system, insects also have a sophisticated hormone signaling network that regulates their developmental transitions. Mainly by using fruit fly molecular genetic tools, we would like to understand what kind of hormones and receptors are involved in this system, how they work at the molecular level, and how such knowledge can be applied to develop new approaches to control animal development."
This is exciting research.
What exactly are "steroid hormones?" As author Sarah Nightingale explained in the UCR news release:
"Steroid hormones mediate many biological processes, including growth and development in insects, and sexual maturation, immunity and cancer progression in humans. After they are produced by glands of the endocrine system, steroid hormones must enter cells to exert their biological effects. For decades, the assumption has been that these hormones enter cells by simple diffusion, but preliminary work in Yamanaka's lab suggests a defined passageway controlled by proteins called membrane transporters."
Said Yamanaka: "The overall goal of this project is to challenge the conventional paradigm in endocrinology that steroid hormones freely travel across cell membranes by simple diffusion. We will also screen chemicals that inhibit steroid hormone entry into cells, with the goal of developing new pest control reagents.”
The NIH High-Risk, High-Reward Research Program is quite competitive. This year NIH officials granted only 89 awards and they were to “extraordinarily creative scientists proposing highly innovative research to address major challenges in biomedical research.”
Yamanaka's research may lead to important pest control strategies for mosquitoes that transmit deadly diseases. As Nightingale explained: "Using the simple but powerful fruit fly model, his team will study how the insect steroid hormone ecdysone is transported in (and potentially out) of cells with the help of membrane transporters. Since ecdysone controls metamorphosis and molting as an insect moves from one stage of its life cycle to the next, blocking its transport could offer a new way to inhibit insect growth and development. The team will then study the same transport pathway in the mosquito that causes yellow fever, hoping to identify chemicals that inhibit steroid hormone transport as a pest control strategy. Worldwide, mosquito-borne diseases cause millions of deaths each year, with malaria alone causing more than 400,000 deaths, according to the World Health Organization."
Bottom line: “By targeting the membrane transporter from outside the cells, we may be able to circumvent common pesticide resistance machinery provided by proteins within the cells, such as detoxification enzymes and drug efflux pumps,” Yamanaka pointed out in the news release.
His seminar at UC Davis is the fifth in a series of fall seminars coordinated by Attardo. (Note: The Yamanaka seminar will not be recorded.)
Upcoming seminars include:
4:10 p.m., Wednesday, Oct. 31
Fred Wolf, assistant professor, UC Merced: (tentative title) "Drunken Drosophila and the Coding of Brain Plasticity"
Host: Joanna Chiu, associate professor and vice chair, UC Davis Department of Entomology and Nematology
4:10 p.m., Wednesday, Nov. 7
Lark Coffey, assistant professor in the Department of Pathology, Microbiology and Immunology, UC Davis School of Veterinary Medicine: "Zika Virus in Macaques, Mice and Mosquitoes: Contrasting Virulence and Transmissibility in Disparate Hosts"
Host: Geoffrey Attardo
Meet Olivia Winokur, an enthusiastic, dedicated and multi-talented medical entomologist whose childhood curiosity about a yellow fever vaccination sparked her interest in 'skeeters.
In her youth, Olivia traveled with her parents and brothers to “off-the-beaten-path” locations. “So I was exposed to vector-borne disease awareness from a young age,” she recalled. “When I was 8 years old, I remember getting the yellow fever vaccination and being curious about why I had to get it for a trip to Southern Africa. I think that was my defining moment when I learned mosquitoes are more than just annoying. Since then, I've slept under many mosquito nets and am no stranger to mosquito bites.”
“I didn't think much about making a career out of those 'skeeters, though. I attended Cornell University as undergraduate, where I studied global public health from multiple perspectives. It wasn't until I became a research assistant in Dr. Laura Harrington's lab that I became fascinated with mosquito biology and decided to pursue a career in medical entomology.”
Winokur, who received her bachelor's degree in 2015 from Cornell University, majoring in Interdisciplinary Studies and focusing on the environmental effects on human health, enrolled in the UC Davis graduate program in 2016 as a Ph.D entomology student with a designated emphasis in the biology of vector-borne diseases.
She studies with major professor and UC Davis alumnus Christopher Barker, associate professor and associate researcher in the Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, who doubles as a graduate student advisor in the UC Davis Department of Entomology and Nematology.
Earlier this year, Winokur received a three-year National Science Foundation Graduate Research Fellowship. A 2017 Bill Hazeltine Memorial Award also helps fund her research.
Her research at UC Davis mainly involves Aedes aegypti, also known as the yellow fever mosquito. “At present, most of the research done on mosquito-borne virus transmission is done under a very narrow range of conditions that reflect a particular mosquito species' 'optimal' rearing and adult environment,” Winokur said. “I'm interested in how conditions outside of this optimal range at both the larval and adult stages affect mosquito-borne virus transmission. I work mostly with Aedes aegypti, which transmits diseases including dengue, Zika, yellow fever, and chikungunya viruses. Currently my research is focused on Zika virus. I hope to determine how the range of conditions mosquitoes encounter outside of the lab alter their life history traits, such as survival and blood feeding behavior, as well as viral transmission so that we can better understand geographical and seasonal mosquito-borne virus risk and eventually mitigate the risk.”
What fascinates her about mosquitoes? “People are usually wowed when I tell them there are over 3500 species of mosquitoes!” she said. “But don't worry.. not all of them transmit human pathogens. I love telling people about the natural history of different genera and species and how this affects the likelihood of pathogen transmission to humans. I'm continually fascinated by how resilient mosquitoes are, how successful they've been throughout history, and how they've completely altered human history. I actually gave a lecture on how vector-borne diseases have altered human history last quarter (Winter 2018) to an undergraduate class led by UC Davis entomology graduate students (Ent10: Natural History of Insects).”
Born in Long Beach, Calif., Olivia grew up in Laguna Niguel, Calif., where she focused on science as a part of the Dana Hills High School Health and Medical Occupations Academy. Olivia also played basketball at Dana Hills and helped the team win its first league title.
What drew her to UC Davis? “I grew up in California so I was familiar with UC Davis from a young age. I actually applied to UC Davis as an undergraduate, but decided to try life on the East Coast instead and attended Cornell University. While at Cornell, I learned a lot about UC Davis as most of my professors had spent some time at UC Davis during their academic tenure, and a lot of the research I was reading was coming out of UC Davis. I was excited to come back to the West Coast for graduate school so UC Davis seemed like an obvious choice!”
Winokur is a co-author of “The Impact of Temperature and Body-Size on Flight Tone Variation in the Mosquito Vector Aedes aegypti (Diptera: Culicidae): Implications for Acoustic Lures," published in April 2017, in the Journal of Medical Entomology. Several other manuscripts are accepted or in preparation.
She has given presentations at the Mosquito and Vector Control Association of California and the American Society of Tropical Medicine and Hygiene.
Dedicated to helping high school girls transition into STEM (Science, Technology, Engineering and Math) careers, Winokur is a founding board member and publicity co-chair of GOALS (Girls' Outdoor Adventure in Leadership and Science). The organization seeks “to cultivate and embolden the next generation of STEM leaders through a free, immersive, field-based summer science program for high school girls.”
“GOALS is for high school girls, inclusive of cis, trans, and gender nonbinary youth who identify with girlhood, to learn science hands-on while backpacking through the wilderness,” Winokur related. “I have worked with an incredible team of UC Davis affiliates to create GOALS to increase opportunities for high school students who identify with girlhood from backgrounds traditionally underrepresented in STEM. Our first trip is happening this summer!” This year's program takes place July 21 to Aug. 5.
Winokur is also a part of the Letters to a Pre-Scientist program “so I get to be a pen-pal to an elementary school student to talk about science!” In addition, she serves as the treasurer of the UC Davis Entomology Graduate Student Association.
Delighted to return to California after being on the East Coast, Winokur spends her leisure time outdoors hiking and backpacking “and exploring the beautiful places near Davis like the Lake Tahoe area and Yosemite. I taught backpacking and wilderness survival skills for Cornell Outdoor Education during college. Additionally, I'm a trivia nerd so I watch a lot of Jeopardy! and play pub trivia with my entomology colleagues weekly. I also enjoy drawing, reading, playing board games, and doing jigsaw puzzles. When I get the chance I enjoy traveling as well--I just returned from Belize and I'll be in Denmark in July!”
After finishing her Ph.D., Winokur plans to remain in academia, but “I'm unsure exactly what that will look like! I really enjoy research, teaching, and mentoring so I'd like to have a career where I can do all of these. I also plan to have a career where I can conduct translational research with broad global health implications, engage non-scientists, create tools to help decision makers mitigate vector-borne disease burden worldwide, and encourage interest and diversity in STEM.”
What does climate have to do with it? And other factors?
Kilpatrick will present a seminar, hosted by the UC Davis Department of Entomology and Nematology, on "Climate, Chemicals and Evolution in the Transmission of Vector-Borne Diseases" at 4:10 p.m., Wednesday, Feb. 7 in 122 Briggs Hall.
"I will integrate findings from multiple systems, including West Nile, Zika and dengue viruses, and mosquito communities more generally, to explore the role of climate, insecticides, host-pathogen interactions, and evolution in driving spatio-temporal patterns of transmission, and the impact of vector borne diseases on their hosts," he says.
Kilpatrick says "the globalization of trade and travel will continue to move viruses, vectors and hosts to new continents and result in the emergence of vector borne diseases, as exemplified by Zika, Chikungunya and West Nile viruses. A sound understanding of the ecology and evolution of these systems is needed to address this challenge."
Kilpatrick received two bachelor's degree from UCLA (one in mechanical engineering and the other in philosophy), a master's degree in mechanical engineering from Massachusetts Institute of Technology, and a doctorate in zoology from the University of Wisconsin, Madison. He joined the UC Santa Cruz faculty in 2008 after working as a senior research scientist in the Consortium for Conservation Medicine in New York.
"My research unites theory and empirical work to address basic and applied questions on the ecology of infectious diseases as well as population biology, evolution, climate, behavior, genetics, and conservation, and I would be excited to develop collaborations and advise graduate students in any of these areas," Kilpatrick says on his website. "A key aim is to understand the underlying drivers of pathogen transmission and the impacts on host populations. My general research philosophy is to begin each project by developing a model of the system to generate hypotheses and then test these hypotheses by gathering empirical data. My current research can be divided into three general areas:
- Local determinants of pathogen transmission,
- The impact of disease on animal populations, and
- The spread of pathogens to new regions.
He focuses much of his current work in disease ecology on West Nile virus, "a mosquito-transmitted pathogen that currently causes thousands of human cases each year, as well as affecting millions of animals. However, I also work on several other pathogen systems including chytridiomycosis, Lyme disease, Brucellosis, and avian influenza."
The American Ornithologists' Union awarded him the Ned K. Johnson Young Investigator Award in 2008. The award recognizes outstanding and promising work by researchers early in their career. "Kilpatrick's research on avian influenza ("bird flu") has led to predictions about the global spread of the virulent H5N1 strain of the virus," according to a UC Santa Cruz news story. "His research on West Nile virus includes a recent study on the effects of higher temperatures on transmission of the virus by mosquitoes. He has also shown a connection between increases in human infections and dispersal of American robins, the preferred host of a mosquito species that is an important vector of West Nile virus."
Travelers know Iquitos as the "capital of the Peruvian Amazon" but scientists know it as a hot spot for dengue, a mosquito-borne viral disease with raging outbreaks in many tropical and subtropical countries.
Amy Morrison, stationed in Iquitos full-time, has directed dengue research activities there for the past 15 years. An epidemiologist who joined the UC Davis laboratory of medical entomologist Thomas Scott (now professor emeritus) in 1996, she's a project scientist and scientific director of the Naval Medical Research Unit No. 6 (NAMRU-6) Iquitos Laboratory.
Morrison is back in the states to present a UC Davis seminar on "Targeting Aedes Aegypti Adults for Dengue Control: Infection Experiments and Vector Control in Iquitos" from 4:10 to 5 p.m., Wednesday, Jan. 10, in 122 Briggs Hall, Kleiber Hall Drive.
Hosted by the UC Davis Department of Entomology and Nematology, it's the first in a series of winter seminars coordinated by assistant professor Rachel Vannette and Ph.D student Brendon Boudinot of the Phil Ward lab.
Dengue is a threat to global health, says Morrison, who holds a doctorate in epidemiology from Yale University and a master's degree in public health from UCLA. According to the World Health Organization (WHO), the incidence of dengue has increased 30-fold over the last 50 years and almost half of the world population is now at risk. It's ranked as "the most critical mosquito-borne viral disease in the world."
"Each year, an estimated 390 million dengue infections occur around the world," according to the World Mosquito Program. "Of these, 500,000 cases develop into dengue hemorrhagic fever, a more severe form of the disease, which results in up to 25,000 deaths annually worldwide."
Of the dengue project in Iquitos, Morrison says: "Comprehensive, longitudinal field studies that monitor both disease and vector populations for dengue viruses have been carried out since 1999 in Iquitos. In addition, to five large scale-vector control intervention trials, ongoing data collection has allowed the evaluation of Ministry of Health emergency vector control using indoor ULV space sprays with pyrethroids in concert with larviciding through multiple campaigns, as well as characterize local DENV (dengue virus) transmission dynamics through two and one novel DENV serotype and strain invasions into the city."
"Our research group has also been conducting contact cluster investigations on DENV-infected and febrile control individuals since 2008," Morrison relates. "These studies demonstrated that attack rates were consistent between houses where cases were first detected and recently visited contact houses independent of distance between these locations. Furthermore, contact cluster investigations allow us to identify viremic individuals across the spectrum of disease outcomes including inapparent infections."
"Using DENV positive individuals captured through these and other febrile surveillance protocols, we exposed laboratory reared (F2) Aedes aegypti mosquitoes directly on their arms or legs, and obtained blood samples with and without EDTA for exposure of mosquitoes in an artificial membrane feeder. After a 58-participant pilot study comparing feeding methods, we initiated a direct feeding protocol exposing participants (78 feeds in 31 participants to date). Feeding, survival, midgut infection and systemic dissemination are all higher using direct feeding than indirect feeding methods. Of 22 participants without detectable fluorescent focus assay titers in their serum at the time they were exposed to mosquitoes, 14 infected mosquitoes by at least one method."
"Although virus titer was a predictor of mosquito infection, mosquitoes became infected at low or undetectable titers and with subjects experiencing mild disease. We have evaluated insecticide-treated curtains and a novel lethal ovitrap (Attractive Lethal OviTrap = ALOT) for dengue control. Only the ALOT traps showed a significant impact on dengue incidence corresponding to a modest decrease in vector densities and a shift of the mosquito population age structure in the trap area to younger mosquitoes. Recent evaluations of indoor ULV interventions with pyrethroids suggest that ULV campaigns that reduce Aedes aegypti for at least 3 weeks through multiple fumigation cycles can mitigate DENV transmission during the same season."
Bottom line: "We argue that Aedes aegypti control should focus on interrupting transmission rather than long-term suppression at operationally unachievable levels and that emergency control should be applied at area-wide scales rather than reacting to individual DENV cases."
Chemical ecologist and mosquito researcher Walter Leal, distinguished professor in the UC Davis Department of Molecular and Cellular Biology, and his lab collaborated with scientists in Recife to ask “Does Zika Virus Infection Affect Mosquito Response to Repellents?”
The work, funded by the National Institutes of Health, was published Feb. 16 in Scientific Reports of the journal Nature. The researchers used mosquitoes originating from colonies reared by UC Davis medical entomologist Anthony Cornel and from colonies in Recife.
“We used assays mimicking the human arm to test the mosquitoes infected with the Zika virus,” Leal said, “and we asked whether the Zika infection affects mosquito response to repellents.” They tested DEET and Picaridin, considered the top two mosquito repellents. “We discovered that DEET works better than Picaridin against the southern house mosquito, Culex quinquefasciatus, and the yellow fever mosquito, Aedes aegypti, whether infected or not.”
The researchers also found that old mosquitoes that already had a blood meal “were less sensitive to repellents,” said Leal, adding “It was not clear whether this was due to the virus, but mostly likely because of age. ”
“Lower doses--normally used in commercial products--work well for young mosquitoes,” Leal said, “but the old ones are the dangerous ones because they may have had a blood meal infected with virus and there was enough time for the virus to replicate in the mosquito body.”
“The bottom line: to prevent bites of infected mosquitoes, higher doses of repellent are needed. The data suggest that 30 percent DEET should be used. Lower doses may repel nuisance young mosquitoes, but not the dangerous, infected, old females.”
Leal, a native of Brazil, collaborates with Rosangela Barbosa and Constancia Ayres of the Oswaldo Cruz Foundation (FIOCRUZ-PE), Recife, Brazil. The work with infected mosquitoes was conducted at FIOCRUZ-PE.
Leal, Barbosa and Ayres co-authored the paper with Fangfang Zeng and Kaiming Tan, both of the Leal lab; and Rosângela M. R. Barbosa, Gabriel B. Faierstein, Marcelo H. S. Paiva, Duschinka R. D. Guedes, and Mônica M. Crespo, all of Brazil.
The World Health Organization (WHO) recommends that people traveling to or living in areas with Zika virus (ZIKV) outbreaks or epidemics adopt preventive measures, including the use of insect repellents, to reduce or eliminate mosquito bites. Prior to the Feb. 16 published research, it was not known whether the most widely repellents are effective against ZIKV-infected mosquitoes, “in part because of the ethical concerns related to exposing a human subject's arm to infected mosquitoes in the standard arm-in-cage assay,” the researchers pointed out.
They used a previously developed, human subject-free behavioral assay, which mimics a human subject to evaluate the top two recommended insect repellents.
Scientists isolated the Zika virus (ZIKV) nearly seven decades ago from a sentinel rhesus monkey while they were trying to unravel the cycle of sylvan yellow fever virus in Uganda..
According to the Centers for Disease Control and Prevention:
- Zika is spread mostly by the bite of an infected Aedes species mosquito (Ae. aegypti and Ae. albopictus). These mosquitoes bite during the day and night. The virus can also be sexually transmitted.
- Zika can be passed from a pregnant woman to her fetus. Infection during pregnancy can cause certain birth defects.
- There is no vaccine or medicine for Zika.
- Local mosquito-borne Zika virus transmission has been reported in the continental United States.