R01AI148300

The objective of the proposed R01 project is to build on our recent findings that attractive odors from sources of nectar activate conserved olfactory channels in mosquitoes. We have discovered that the odorant ratios within the scent, along with the inhibition in the antennal lobe (AL), are critical for Aedes aegypti behavior. Feeding on fruits and flowers is a vital behavior for mosquitoes, and their attraction to these sources of nectar is mediated by the ratio of key odorants in the bouquet.

Bait-and-kill traps that use fruit syrups have effectively controlled local mosquito populations. However, variation in the fruit odor can strongly impact its attractiveness. We still have not identified the odor constituents and ratios that are attractive in the nectar odors, which would enable the development of synthetic lures. Furthermore, we do not fully understand how this information is detected and processed by the mosquito's olfactory system.

Nectar-feeding by female mosquitoes increases their life-span and decreases the gonotrophic cycle, thereby increasing their vectorial capacity. For adult males, nectar is the only source of nutrients. Our recent work allowed us to identify the odor constituents that mediate nectar-feeding behaviors in Aedes aegypti and understand how the odor is processed in the brain. Now, in this application, we propose to use a combination of behavioral assays, chemical methods combined with calcium imaging in tethered flying mosquitoes, and genetic approaches to study the olfactory basis of nectar-seeking behaviors.

Aim 1 will allow us to identify attractive odorants in the scents of diverse plant nectar sources and use heterologous expression systems to de-orphan the cognate odorant receptors (ORs). We will also take advantage of the Q-system for genetically characterizing three ORs (OR15, OR49, and OR2) that are essential for representing the proper ratios in nectar odors.

In Aim 2, we will leverage our existing and new GCAMP expression lines to examine how the ratios of these key odorants are processed in the AL, and how GABAergic inhibition shapes these responses.

In Aim 3, we will use our identified odor lures, and artificial lures that vary in their natural ratios of key odorants, to determine their efficacy in bait-and-kill systems.

Together, these experiments will test the working hypothesis that nectar odors and their specific odorant ratios activate conserved olfactory channels to be processed similarly by AL circuits to mediate feeding behaviors. While there has been an extensive study of mosquito attraction to blood hosts, we know comparatively less about nectar feeding. Our experiments will identify new odors that can be immediately deployed as attractant lures. Additionally, GABAergic systems are involved in diverse physiological processes in insect vectors, including olfaction, immune response, and arbovirus replication, as well as being potent targets for insecticides. Generating mutants that target the mosquito's olfactory responses or GABAergic pathways could provide additional insight into these diverse processes.

Sugar feeding plays an essential role in the vectorial capacity of mosquitoes and the spread of diseases that afflict over a billion people annually. Therefore, unraveling the neural bases of nectar-feeding will enable new gene targets and tools for their control.

University Of Washington

TO ASSIST PUBLIC AND PRIVATE NONPROFIT INSTITUTIONS AND INDIVIDUALS TO ESTABLISH, EXPAND AND IMPROVE BIOMEDICAL RESEARCH AND RESEARCH TRAINING IN INFECTIOUS DISEASES AND RELATED AREAS, TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS. TO ASSIST PUBLIC, PRIVATE AND COMMERCIAL INSTITUTIONS TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS, TO PROVIDE RESEARCH SERVICES AS REQUIRED BY THE AGENCY FOR PROGRAMS IN INFECTIOUS DISEASES, AND CONTROLLING DISEASE CAUSED BY INFECTIOUS OR PARASITIC AGENTS, ALLERGIC AND IMMUNOLOGIC DISEASES AND RELATED AREAS. PROJECTS RANGE FROM STUDIES OF MICROBIAL PHYSIOLOGY AND ANTIGENIC STRUCTURE TO COLLABORATIVE TRIALS OF EXPERIMENTAL DRUGS AND VACCINES, MECHANISMS OF RESISTANCE TO ANTIBIOTICS AS WELL AS RESEARCH DEALING WITH EPIDEMIOLOGICAL OBSERVATIONS IN HOSPITALIZED PATIENTS OR COMMUNITY POPULATIONS AND PROGRESS IN ALLERGIC AND IMMUNOLOGIC DISEASES. BECAUSE OF THIS DUAL FOCUS, THE PROGRAM ENCOMPASSES BOTH BASIC RESEARCH AND CLINICAL RESEARCH. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM EXPANDS AND IMPROVES PRIVATE SECTOR PARTICIPATION IN BIOMEDICAL RESEARCH. THE SBIR PROGRAM INTENDS TO INCREASE AND FACILITATE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM STIMULATES AND FOSTERS SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. RESEARCH CAREER DEVELOPMENT AWARDS SUPPORT THE DEVELOPMENT OF SCIENTISTS DURING THE FORMATIVE STAGES OF THEIR CAREERS. INDIVIDUAL NATIONAL RESEARCH SERVICE AWARDS (NRSAS) ARE MADE DIRECTLY TO APPROVE APPLICANTS FOR RESEARCH TRAINING IN SPECIFIED BIOMEDICAL SHORTAGE AREAS. IN ADDITION, INSTITUTIONAL NATIONAL RESEARCH SERVICE AWARDS ARE MADE TO ENABLE INSTITUTIONS TO SELECT AND MAKE AWARDS TO INDIVIDUALS TO RECEIVE TRAINING UNDER THE AEGIS OF THEIR INSTITUTIONAL PROGRAM.

93.855 - Allergy and Infectious Diseases Research

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

Seattle, Washington 981951016 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the total obligations have increased 421% from $637,565 to $3,320,838.