Vector-Borne Disease Research

Chris Barker

VM: Pathology, Microbiology and Immunology

Mosquito-borne diseases, Surveillance (see also: Epidemiology)

My program focuses on the epidemiology and ecology of mosquito-borne diseases, primarily those caused by West Nile, chikungunya, and dengue viruses, and including other livestock diseases such as Rift Valley fever and bluetongue. My research combines laboratory studies and epidemiological methods to understand the environmental drivers of disease outbreaks, and I manage the UC Davis component of the statewide surveillance program for mosquito-borne viruses.

STAR project opportunities in my lab include [1] development of laboratory assays to monitor feeding by individual mosquitoes over time (methods: MALDI-TOF, mosquito rearing and handling) , [2] experiments to define the relationship between temperature and incubation of chikungunya virus in mosquitoes (methods: RT-PCR, MALDI-TOF, mosquito rearing and handling), or [3] analysis of the relationship between West Nile virus risk and drought in California (methods: epidemiology, GIS, basic statistics).

Dr. Barker can be reached via email at cmbarker@ucdavis.edu.

Nicole Baumgarth

Center for Comparative Medicine; Immunity to infectious diseases (See also: Immunology/Infectious Diseases)

Dr. Baumgarth is a veterinarian and research immunologist with broad interests in infectious disease immunology. An underlying theme of all research studies in her laboratory is the use of mouse models to dissect the complexity of host-pathogen interactions. For that she has developed new technologies that allow a precise assessment and analysis of in vivo immune events. A major focus of her research involves studies on the regulation of early antiviral B cell immune responses to influenza virus. Ongoing work is directed towards identifying mechanisms by which infection-induced innate cytokines regulate the earliest events that trigger antiviral B cells responses. Members of her lab are working on the concept that innate cytokines regulate the thresholds by which lymphocytes are activated to participate in immune responses in order to avoid the negative consequences of a potentially overshooting immune response (autoimmunity). She is also involved in studies to delineate the causes for the lack of protective immunity to the Lyme disease pathogen Borrelia burgdorferi. Using a mouse model established by her collaborator, Dr. Barthold, they are following their earlier observations that B. burgdorferi subverts the B cell response to this pathogen, with the long-term goal to find targets for therapeutic intervention that could bolster the immune response of an infected individual to clear this bacterial infection.

Please visit Dr. Baumgarth's website at: https://ccm.ucdavis.edu/faculty/baumgarth/

Lark L. Coffey, Ph.D.

Davis Arbovirus Research and Training
Center for Vectorborne Diseases
Assistant Professor
Department of Pathology, Microbiology and Immunology

(See also: Microbiology/Parasitology, Pathology/Virology)

Dr. Coffey  studies the ecology, evolution, and transmission dynamics of mosquito-borne viruses including chikungunya, Zika, West Nile, and St. Louis encephalitis that are significant causes of human disease with no licensed human vaccines or treatments beyond supportive care. The goal of her research is to understand patterns of viral molecular evolution and the viral genetic factors that promote arbovirus emergence and severe disease. Her work focuses on how intrahost viral genetic diversity generated by error-prone viral replication influences infectivity and transmissibility between mosquitoes and people or animals. She and her team also developing cheap and convenient improvements to surveillance in mosquitoes by detecting viral RNA in saliva expectorated by sugar-feeding West Nile virus vectors in California. They are also developing approaches to increase safety of candidate live-attenuated chikungunya virus vaccines by restricting their potential to develop revertant mutations that cause illness in vaccinees. Together with the California National Primate Research Center, the team is developing a non-human primate model of human Zika virus in pregnancy that is being used to define the roles of Zika virus mutations in fetal disease and for pre-clinical testing of therapies and vaccines. 

Please see http://coffeylab.ucdavis.edu for more information.

Janet Foley, DVM, PHD

Center for Vectorborne Diseases

Tick-borne diseases

Summer veterinary students have several opportunities from which they can choose a summer project. The emphasis in the laboratory is disease ecology, epidemiology, and theory of infectious diseases, primarily in vector-host-pathogen systems although there are several non-vector transmitted diseases being studied as well. Students should expect to work every day all day, learn laboratory and/or field skills appropriate to their interests and project, and meet with Dr. Foley as early as possible (preferably in the spring) to confirm a project. Skills will be acquired through work with other students, technicians, and faculty in the laboratory; once a veterinary student is comfortable, they may expect to spend much of the rest of the summer obtaining data relevant to their project, analyzing the data with faculty supervision, and hopefully prepare it for publication.

Please visit Dr. Foley's website at: http://faculty.vetmed.ucdavis.edu/faculty/jefoley/

Gregory Lanzaro, PhD

Vector Genetics Lab

Variation in maxadilan and its consequences

Maxadilan is a potent vsodilatory protein in the saliva of the sand fly, Lutzomyia longipalpis . Our observation that maxadilan is highly polymorphic was surprising. It would seem that the amino acid sequence of such a protein, with functions presumably vital to the sand fly, would be conserved. We hypothesize that hyper-variation in maxadilan has evolved as a mechanism for the avoidance of host immune response mounted against it. To test this hypothesis we propose studies aimed at determining amino acid sequence polymorphism in maxadilan from Lu. longipalpis (Aim #1). Population genetics studies will be conducted at field sites in Colombia , Nicaragua and Brazil . If variation in maxadilan does represent antigenic polymorphism and is adaptive, then it must be true that anti-maxadilan antibodies have a negative effect on vector fitness. In Aim #2 we propose a series of experiments to test this hypothesis. We will immunize hamsters with recombinant maxadilan. Flies will be fed on immunized and control animals and effects on sand fly fitness evaluated. In Aim #3 we will examine the impact of maxadilan on leishmanial infections. There is compelling evidence that the immunomodulatory activities of sand fly saliva, and maxadilan itself, enhances the establishment of parasite infections. The effects of vector saliva and specific maxadilan proteins on the pathogenesis of Leishmania chagasi will be evaluated by experimental infections (Aim #3). We have discovered that natural Lu. longipalpis populations differ dramatically in the amount of maxadilan present in their saliva. As part of Aim #3 we will conduct epidemiological field studies to determine the distribution of “high” and “low” maxadilan fly populations in relation to the distribution of visceral or atypical cutaneous disease caused by Le. chagasi . In Aim #4, we will study immunological specificity of maxadilan variants. The goal of these experiments is to determine if different maxadilan proteins illicit specific antibodies and to evaluate if these cross react (antigenic specificity).

Population genomics of the mosquito An. gambiae in Africa

Malaria control strategies based on genetic manipulation of vectors will require extensive knowledge of vector population genetics. Critical information includes: population size, patterns of gene flow, the breeding structure of populations and the effects of natural selection on individual gene loci. The overall goal of the proposed research is to provide such a background. We propose to address these questions by: (1) Characterizing spatial variation in the genetic structure of populations of Anopheles gambiae in continental Africa by determining the distribution of chromosomal and molecular polymorphisms. Representative locations will be studied in two countries: Mali in West Africa and Cameroon in Central Africa . The genetic markers we will use include chromosome arrangements, microsatellite DNA loci, and mitochondrial DNA loci. (2) Identifying physical/ecological features and relate these to spatial varoiation in population genetic structure, patterns of gene flow, and as selective forces on individual loci. Migration rates among sites will be established by measuring their genetic similarity, then inferring how much gene flow is required to maintain such observed similarity. Based on this information we will employ a GIS-based procedure termed "Wombling", which will identify areas with high and low levels of gene flow. These will be then be correlated with ecological features determined on the ground and from remote imaging. In this manner ecological features associated with high and low population densities, and also with high and low levels of gene flow can thus be identified. Such information should be helpful to vector control efforts that require an understanding of dispersal and gene flow, including genetic control and insecticide resistance management. The effects of natural selection on individual loci and segregating sites within loci will be studied by taking a population genomics approach. This approach provides the means to study the behavior of individual functional genes in nature, bridging the gap between population genetics and molecular biology.

Please visit Dr. Lanzaro's website at: http://faculty.vetmed.ucdavis.edu/faculty/gclanzaro/