- Author: Kathy Keatley Garvey
"We are working with scientists and public health authorities in STP to establish the conditions that would facilitate an informed societal and government decision about a proposed release of Anopheles mosquitoes engineered to prevent transmission of the malaria parasite Plasmodium falciparum on the islands,” said principal investigator Gregory Lanzaro, director of the Vector Genetics Laboratory and a PMI professor.
This award will be used to extend their ongoing entomological, engagement and capacity building work through 2025.
“We are working in collaboration with the UC Irvine Malaria Initiative (UCIMI), a research consortium including scientists from UC Irvine, San Diego and Berkeley as well as Johns Hopkins University,” Lanzaro said. “We are working toward the application of advanced genetic tools aimed at the mosquito vector. It is our belief that this approach, used in conjunction with early malaria treatment and detection, can provide a cost effective, sustainable, and environmentally responsible program to ultimately eliminate malaria from Africa.”
Said Ana Kormos, engagement program manager and lead author of the proposal: “These funds provide the UCIMI program with support to strengthen our existing relationship-based approach to the co-development of this technology and ensures that our partners in STP lead the decision-making processes involved in all aspects of the research. This is a huge step forward in advancing a truly collaborative approach to translational research.”
The Vector Genetics Laboratory is engaged in research and training in the areas of population and molecular genetics, genomics and bioinformatics of insect vectors of human and animal disease. The website: “We have developed a program aimed at expanding knowledge that may be applied to improving control of disease vectors and that also addresses problems of interest in the field of evolutionary genetics. We are currently engaged in a range of projects, but our major research focus is on vectors of malaria in Africa."
Directors of the Vector Genetics Laboratory research programs are Lanzaro and Anthony "Anton" Cornel, a research entomologist with the UC Davis Department of Entomology and Nematology and director of the Mosquito Control Research Laboratory, Parlier.
New Tools. "The fight to reduce and possibly eliminate malaria continues and becomes especially challenging as efforts to reduce malaria morbidity have plateaued since 2015,” said Cornel. “Therefore, we must seriously consider new tools. One such tool is genetically modifying the major mosquito vector in the Afrotropics so that it cannot transmit malaria."
"The project aims to use genetically modified (GM) mosquito strategy to reduce and eliminate malaria from the Islands of São Tomé and Príncipe, as proof of concept, before using this technology on larger scales on mainland Africa,” Cornel said, adding that his role, as a field team co-investigator for UCIMI and VGL, is to work with Lanzaro and Pinto “to understand as much as we can about the behavior, population structure and population sizes of Anopheles coluzzi (the malaria vector) on these islands to design the most efficient strategy of releasing the genetically modified mosquitoes to have maximum effect.”
Malaria is an acute illness caused by Plasmodium parasites, which spread to humans through the bites of infected female Anopheles mosquitoes, according to the World Health Organization (WHO). In 2020, nearly half of the world's population was at risk of malaria. An estimated 241 million cases of malaria occurred worldwide in 2020, with 627,000 dying.
Tremendous Burden. Medical entomologist and geneticist Geoffrey Attardo of the UC Davis Department of Entomology and Nematology (who is not involved in this project), noted that “Malaria is a disease which creates a tremendous burden on people living in affected areas. In particular its impacts on the mortality in young children and pregnant women are devastating. Attempts to control this disease using traditional methods have been effective in recent years.”
The island nation of São Tomé and Príncipe, population of 178,700 in 2016, is located about 200 miles west of Gabon on Africa's mainland. It shares maritime borders with Equatorial Guinea, Gabon, and Nigeria. The combined area of the archipelago is about five times the size of Washington, DC. The United States established diplomatic relations with São Tomé and Príncipe in 1976, following its independence from Portugal.
Open Philanthropy's mission, as noted on its website, is to “give as effectively as we can and share our findings openly so that anyone can build on our work. Through research and grant-making, we hope to learn how to make philanthropy go especially far in terms of improving lives. We're passionate about maximizing the impact of our giving, and we're excited to connect with other donors who share our passion.”
Resource:
São Tomé and Príncipe (nationsonline.org)
- Author: Kathy Keatley Garvey
The yellow fever mosquito, Aedes aegypti, a newly invasive species in central California? Check.
The West Nile virus mosquito, Culex quinquefasciatus, found throughout much of the world? Check.
The malaria mosquito, Anopheles gambiae, which wreaks worldwide havoc? Check.
Cornel's name appeared in the news this week when the UC Davis lab of Walter Leal announced that it had found the odorant receptor that repels DEET in the southern house mosquito, Culex quinquefasciatus mosquito. Cornel provided the mosquitoes that allowed the Leal lab to duplicate his colony. Proceedings of the National Academy of Sciences (PNAS) published the work Oct. 27.
Cornel's main research keys in on the population genetics and ecology of West Nile virus vectors in the United States and population genetics and ecology of major malaria vectors in Africa.
“Anton is a great asset to our program, a wonderful colleague, and a nice team player,” said Leal, a professor in the Department of Molecular and Cellular Biology. “We benefit greatly from his generosity by sharing not only mosquito colonies, but also his encyclopedic knowledge on mosquito biology and ecology. We shared co-authorship in a number of publications, and many more are coming.”
Cornel collaborates with Leal on oviposition attraction in Culex quinquefasciatus and “we are now endeavoring to come up with effective oviposition attractive chemical lures to use in virus surveillance and kill traps.”
“The invasion of Aedes aegypti into central California has been of great concern especially as current control methods do not appear to be working very well,” said Cornel, who works closely with state's mosquito abatement personnel. “We have found that the Aedes aegypti have insecticide resistance genes which likely explains why their ultra-low volume (ULV) and barrier spray applications have not worked as well as expected. Work will be ongoing next year when the Aedes aegypti become active again after a brief slow overwintering period from November to March.”
A native of South Africa, Cornel received his doctorate in entomology, focusing on mosquito systematics, in 1993 from the University of the Witwatersrand, Johannesburg. He completed a post-doctoral fellowship with the Entomology Branch of the Centers for Disease Control and Prevention, Atlanta, before joining UC Davis in 1997 as an assistant professor and researcher.
“Who would have thought that that the expertise that I gained on West Nile virus as a master student in South Africa would be used many years later after West Nile virus invaded and spread throughout the USA?”
For more than two decades, Cornel has teamed with fellow medical entomologist and “blood brother” Professor Gregory Lanzaro of the UC Davis School of Veterinary Medicine to study malaria mosquitoes in the West African country of Mali. Their work is starting to show significant results.
“Because of our commitment to conduct long term longitudinal studies and not static investigations,” Cornel said, “we have now shown that considerable selective processes are taking place causing spatiotemporal dynamics of gene flow and fitness events in major malaria vectors M (now Anopheles coluzzii) and S (now Anopheles gambiae) and M/S hybrids in West Africa.” Their work was published in PNAS in 2013 (vol:110:49).
“We are currently establishing further evidence of the important role of insecticide resistance traits in spatiotemporal dynamics of Anopheles coluzzii, Anopheles gambiae and the Bamako form.” Cornel noted that these results have “considerably important implications in future efficacies of insecticide treated bednets to control indoor biting malaria vectors in West Africa.”
Cornel also teams with Lanzaro and Professor Heather Ferguson of the University of Glasgow to examine the ecology and associated genetics of the major malaria vector Anopheles arabiensis in Tanzania. They began working on the project four years ago.
“We are looking at the effects of bednet use and changes in feeding patterns of this mosquito taking population structure into consideration,” Cornel said. He and his colleagues published a paper in November 2013 in G3: Genes, Genome and Genetics, titled “Diversity, Differentiation, and Linkage Disequilibrium: Prospects for Association Mapping in the Malaria Vector Anopheles arabiensis."
One of his newest projects is the study of population/genetics, insecticide resistance and cytogenetics in the major malaria vector in Brazil. Cornel and Lanzaro launched their study in September when they traveled to Brazil to begin targeting the culprit, Anopheles darlingi, a “widely distributed species that has adapted to survive in multiple ecological zones and we suspect that it may consist of multiple incipient or closely related species,” Cornel said.
“While in Brazil I collected larvae and dissected salivary glands from them to examine their polytene chromosome inversion structure and polymorphisms,” Cornel related. “Inversions are vitally important to consider in genetic analyses and it takes considerable patience to interpret the chromosomes.”
Cornel and Lanzaro collaborate with Professor Paulo Pimenta of the Laboratory of Medical Entomology, René Rachou Research Centre- FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil. The UC Davis medical entomologists hope to produce good preliminary data from their research trip to write grants and establish a long-term project in Brazil.
Cornel also studies avian malaria. That interest sparked four years ago when he began working in Cameroon with scientists from UCLA and San Francisco State University (SFSU), including SFSU's Ravinger Sehgal, who studies avian blood parasites. Cornel's graduate student Jenny Carlson, in her final year of her Ph.D studies, is investigating avian malaria in Fresno County.
The Cornel-Carlson research implicates that considerable fidelity exists between Culex mosquito species and species of plasmodium they transmit. “This is contrary to the currently held belief that all Culex mosquitoes are equally capable of transmitting avian malaria,” Cornel said. “In our investigations, we described a new species of avian malaria which is very common in songbirds in Fresno County (published in Parasitology Research).”
Cornel plans to continue working with Sehgal investigating the effects of deforestation on transmission of avian parasites in Cameroon. They recently submitted a National Science Foundation grant proposal. “A large swath of primary forest is slated to be deforested in Cameroon and replaced with Palm oil plantations and we will investigate the effects of this hopefully, as it happens.”
Cornel will be starting a new mosquito-borne virus project in February. He received a Carnegie Foundation scholarly three-month fellowship to work in South Africa (February through to April). The primary objective of the project? To examine mosquito-borne viruses cycling in seven national parks in South Africa and two National Parks in Bostwana.
“It's extremely difficult to get permission to conduct field research in national parks in Southern Africa and this provides an unprecedented exciting opportunity for me to work with a friend, Professor Leo Braack from the University of Pretoria, in these parks. One has to be very careful working in some of these parks at night because of the wild predators, elephants, hippos and buffalo.”
Cornel is active in the 30- member Center for Vectorborne Diseases (CVEC), headquartered in the UC Davis School of Veterinary Medicine and considered the most comprehensive vectorborne disease program in California. Both interdisciplinary and global, CVEC encompasses biological, medical, veterinary and social sciences. Globally, the major emphasis is on research and education involving diseases such as malaria, dengue and leishmaniasis in the developing world. CVEC members study molecular biology, virology, parasitology, vector control, and epidemiology of vectorborne diseases. In addition, the center serves as the principal teaching resource for undergraduate and graduate courses in all facets of vector-borne disease sciences.
Related Links:
Proceedings of the National Academy of Sciences (research paper, PDF)
Research from Walter Leal Lab on DEET
Close Connections (Like Father, Like Son)
- Author: Kathy Keatley Garvey
It promises to be a day of innovation, knowledge-sharing and collaboration, announced Kay Monroe of Zagaya, the event host.
Among the UC Davis researchers participating will be Gregory Lanzaro, professor, and Yoosook Lee, assistant researcher in the Department of Pathology, Microbiology and Immunology (PMI) in the School of Veterinary Medicine and Shirley Luckhart, professor in the Department of Medical Microbiology and Immunology, UC Davis School of Medicine. Lanzaro and Luckhart are graduate student advisors in the UC Davis Department of Entomology and Nematology.
Lanzaro's Soundbite presentation,"Malaria in the Americas: A New Research Initiative for the UC Davis Vector Genetics Lab," will key in on the challenges of malaria control in Brazil. Lee's Soundbite presentation will be on a new diagnostic tool for malaria mosquito research. Luckhart is scheduled for both a Soundbite and poster.
Two of the UC Davis presenters, Laura Norris and Bradley Main, are National Institutes of Health T32 postdoctoral fellows. They will cover the topic of malaria vector evolution in the face of insecticide pressure from bed net campaign.
The schedule of events will be presented the day of the symposium.
The list of the other UC Davis presenters, as announced by Monroe:
Nazzy Pakpour, Soundbite; and Elizabeth Glennon, Kristen Lokken, Jason Maloney, Jose Pietri, Rashaun Potts and Lattha Souvannaseng, Bo Wang, poster.
Keynote speakers are:
- Tim Wells, chief scientific officer, Medicines for Malaria Venture, Geneva, Switzerland, who will share the latest efforts to develop new drugs aimed at wiping out malaria.
Title: The Pipeline of Medicines to Support Malaria Control and Elimination
View abstract
Joseph DeRisi, professor and vice chair of the Department of Biochemistry and Biophysics, UC San Francisco, and a Howard Hughes Medical Institute investigator, who will talk about work in his lab. - Title: "A View from the Trenches – Anti-malarial Drug Development"
View abstract - Regina Rabinovich, ExxonMobil Malaria Scholar in Residence at the Harvard School of Public Health, who will examine the future of malaria eradication efforts, past the 2015 UN Millennium Development goals.
Title: "Beyond the Millennium Development Goals Horizon – What Will Help Drive Success Post-2015?"
View abstract
This year Zagaya has added to the symposium, "The Malaria Artwork Showcase," designed to display artistic representations of malaria, from the molecular to the global scale. The Lanzaro lab will be among those participating in the showcase.
Officials at Zagaya (which means "spear") say this is a critical time for malaria research professionals to come together, as it's one year away from the 2015 UN Millennium Development goal of halting and reversing the growth of malaria incidence. The symposium provides the forum for researchers, implementers, advocates and students to "inspire and catalyze change for the greater good."
Registration is open and ongoing until the day of the event. General registration is $50, and students, $25. A portion of the registration fee--$10--will go toward purchasing bed nets via the United Nation's Nothing but Nets program, a global, grassroots campaign to save lives by preventing malaria.
"Every 45 seconds a child in Africa dies from malaria, a disease spread by a single mosquito bite," according to the From Nothing But Nets website. "There are more than 200 million cases of malaria each year, and nearly 1 million of those infected die from the disease — most of them children under the age of five." Ten dollars can fund a life-saving, insecticide-treated bed net to protect a family in Africa. The nets are considered one of the most cost-effective tools to prevent the spread of malaria. Bed nets have been shown to reduce malaria transmissions by 90 percent in areas with high coverage rates.
For question about the symposium, email Monroe. Anyone interested in volunteering at the symposium should email volunteer coordinator, Gladys De Leon.
- Author: Kathy Keatley Garvey
The lecture, "Anthropogenic Forces Drive the Breakdown of Reproductive Isolation between Incipient Species of the African Malaria Mosquito," is from 12:10 to 1 p.m. in Room 122 of Briggs Hall. Plans are to record the lecture for later viewing on UCTV.
Lanzaro, who researches malaria vectors in Africa and Brazil says his area interest is in medical entomology with a focus on the genetics of vectors of human disease. He initiated his current work on the population genetics of malaria vectors in Africa in 1991 when he joined the Laboratory of Malaria Research at the National Institutes of Health and continues this work through today.
"A considerable part of our research program involves field work," he said. "Over the years we have worked in seven countries spanning sub-Saharan Africa." His Africa work is organized into three major research areas: (1) Genetics of complex behavioral phenotypes, host preference and adult resting behavior (2) Mutations in immune signaling pathway genes and mosquito susceptibility to malaria infection and (3) Speciation in anopheline mosquitoes.
"Just this year we have initiated a new research program focused on the genetics malaria vectors in Brazil," Lanzaro related. The Brazilian government supports the program, known as Brazil Science without Borders. The focus is on the population genetics and genomics of the mosquito Anoheles darlingi, the principal vector of malaria in Brazil.
The abstract of his talk on Nov. 13: "The M and S forms of Anopheles gambiae have been the subject of intense study by both malaria researchers and evolutionary biologists.The focus has centered on evaluating models of the evolution and maintenance of genetic divergence between the two forms in relation to speciation. The two forms occur in sympatry throughout west and central Africa. Hybrids are rarely found in nature and studies of reproductive isolation confirmed strong assortative mating with inter-form matings estimated at a frequency of ~1%. Progeny of laboratory crosses and backcrosses show no signs of reduced fitness, however, it is widely held that, in nature, some degree of ecologically dependent postzygotic isolation, in addition to assortative mating, contributes to divergence between the two forms. Comparative genomics studies have revealed divergence occurs at three discrete islands in genomes that are otherwise nearly identical. Two opposing models aimed at describing the evolution of M and S have been formulated. An 'islands of speciation' model proposes that diverged regions contain “speciation genes” that are maintained by selection in the face of gene flow. An alternative 'incidental island' model maintains that gene flow between M and S is effectively zero and that divergence islands are unrelated to speciation. A 'Divergence Island SNP' (DIS) assay was developed and used to explore the spatial and temporal distributions of hybrid genotypes. Results revealed that hybrid individuals occur at frequencies ranging between 5-97% in every population examined. A temporal analysis of DIS genotype frequencies spanning 20 years was conducted at a single site. This study revealed that assortative mating is unstable and periodically breaks down resulting in extensive hybridization. Results suggest that hybrids suffer a fitness disadvantage, but at least some hybrid genotypes are viable. Stable introgression of the 2L speciation island occurred at this site following a hybridization event. We present data suggesting that strong selection on a single gene within the 2L island is driving M/S introgression and that man-made changes to the environment is the source of this selection."
Lanzaro joined PMI in July 2006. He served as the director of the Center for Vectorborne Diseaes, UC Davis, from January 2006 through June 2007, and directed the UC Mosquito Research Program, headquartered in the UC Davis Department of Entomology, from June 2002 to 2008.
Prior his appointment at UC Davis, Lanzaro served on the faculty of Department of Pathology, University of Texas Medical Branch, Galveston, Texas, from August 1995 through May 2002, advancing from assistant and associate to full professor.
Lanzaro received his bachelor of science degree in biology/secondary education from Kansas State University, Manhattan, Kansas in 1972; his master's degree in entomology in 1978 from the Univeristy of Arizona, Tucson, and his doctorate in engomology in 1986 from the University of Florida.
The medical entomologist did post-doctoral work at three universities: from 1986 to 1988 in the Department of Entomology, Mississippi State University; from 1986 to 1988 in the Department of Entomology, Missisippi State University; and from 1988 to 1991 in the UC Davis Department of Entomology. He was a MacArthur Fellow in the Laboratory of Malaria Research, National Institutes of Health.