2008 Annual Report
1a.Objectives (from AD-416)
Objective 1: Discover and develop next generation topical skin repellents, spatial repellents, contact irritants, and toxicants against mosquitoes and other arthropod disease vectors. Research toward this objective will primarily involve a consortium of military, government, academic, and private industry research groups using high throughput bioassays to test model compounds selected via computational chemistry from the large chemical library maintained by the BASF Corporation.
Objective 2: Develop new technology for preparation of fabrics having insect controlling and/or repelling properties. Repellent compounds will be covalently bonded to fabric polymers, and the resulting polymers will be tested to determine if repellent activity against mosquitoes is retained; if these derivatized polymers are repellent, then research will continue to optimize conditions required to produce insect repellent fabrics.
Objective 3: Identify the mechanisms underlying the activity of key mosquito repellents and attractants, and develop ways to exploit the mechanisms for commercial use. This objective will focus on state-of-the-art application of odorant binding protein (OBP) research by covalently bonding cloned mosquito OBPs to HPLC columns for use in screening natural product and synthetic chemical libraries for binding activity. Bound compounds will be identified and tested in conventional behavioral bioassays for activity against mosquitoes. Also, the mechanisms of action for selected compounds will be investigated electrophysiologically, including single cell recording experimentation to pinpoint the sites of receptors involved in the perception of bioactive compounds.
1b.Approach (from AD-416)
Discover and develop next generation topical skin repellents, spatial repellents, contact irritants, and toxicants against mosquitoes and other arthropod disease vectors.
Develop new technology for preparation of fabrics having insect controlling and/or repelling properties.
Identify the mechanisms underlying the activity of key mosquito repellents and attractants, and develop ways to exploit the mechanisms for commercial use.
The focus of our research is the discovery and development of methods to protect people from medically-important insects and other blood-sucking arthropods that transmit disease agents. Research can be divided into fundamental research aimed at identifying the underlying mechanisms involved in mosquito attractancy and repellency, and applied research aimed at discovering and developing new repellents and toxicants. In fundamental research, methodology using a gaschromatograph/massspectrometer coupled to an electroantennagram was developed to determine potential mosquito attractants and/or repellents and facilitate their identification. A new olfactometer was also designed and constructed as a tool to determine behavioral responses of genetically-modified mosquitoes to attractants and repellents. Volatiles were collected from mosquitoes for analyses and testing for potential chemical signals. In behavioral studies using a flight tunnel, two mosquito species were used to elucidate the stimuli associated with host seeking, landing, probing, and feeding. The results of this research will enhance our fundamental understanding of mosquito host finding and feeding behavior as well as the cellular and subcellular mechanisms involved in attractancy and repellency. This research relates to NP 104 components 3.2 Neural, Sensory, and Reproductive Biology - 3.2.2 Characterize and isolate pheromones and other social cues used by ants and termites in colonization and foraging, and by diptera and ticks in mating and host finding and 3.2.3 Develop measurements of electrophysiological activation for use in selecting vector repellents. The applied thrust of our research program involves the discovery and synthesis of natural and synthetic repellents and toxicants. Natural products, compounds isolated from a variety of plant material, as well as synthetic compounds, those chemically-modified in the laboratory from known insecticides were tested in the laboratory against a variety of blood sucking arthropods including mosquitoes, sand flies, and ticks. To facilitate the laboratory testing of different chemicals for repellency, a method was developed using commercially-available beef collagen and acidified water to produce a thin, artificial membrane capable of being used in bioassays that require blood-feeding. Attempts to prepare similar membranes using commercially-available chicken collagen were unsuccessful and a spectroscopic study of the two membranes has been undertaken to determine why certain collagens are better than others in membrane preparation and if chemical treatment of the starting material can alter the results. This research relates to NP 104 components 4.1 Chemical Pesticides and Repellents - 4.1.1 Develop the capacity to test existing compounds for toxicity against diptera and ticks that transmit disease and 4.1.3 Identify and test new classes of topical and area repellents from previously synthesized or natural volatiles. Develop carrier formulations.
Discovery of a new natural product arthropod repellent. New, effective and inexpensive repellents are needed to protect humans from disease agents transmitted by flies and ticks. Using a laboratory assay system, scientists have shown that a new compound derived from a pine oil chemical deterred the biting activity of mosquitoes more effectively than a widely used synthetic chemical repellent and was also effective against ticks. A method for making this compound was also developed and a U.S. patent was granted ("Methods for preparing isolongifolenone and its use in repelling arthropods", Patent No. U.S. 73,378.557). This compound has the potential to help protect human populations against diseases transmitted by blood-sucking arthropods because it can be produced inexpensively in ton quantities from a sustainable pine oil feed stock. This accomplishment addresses NP 104 Component 4.1.3 "Identify and test new classes of topical and area repellents from previously synthesized or natural volatiles. Develop carrier formulations."
5.Significant Activities that Support Special Target Populations
|Number of Active CRADAs||1|
|Number of Invention Disclosures Submitted||1|
|Number of New Patent Applications Filed||1|
|Number of Newspaper Articles and Other Presentations for Non-Science Audiences||1|
Grieco, J.P., Achee, N.L., Chareonviriyaphap, T., Suwonkerd, W., Chauhan, K.R., Sardelis, M., Roberts, D. 2007. A new classification system for the actions of IRS chemicals traditionally used for malaria control. PLoS ONE 2(8):e716.