SYSTEMS BIOLOGY INVESTIGATIONS OF ARTHROPOD-BORNE DISEASES TO CONTROL VECTORS OF PATHOGENS
Tick and Biting Fly Research
Project Number: 3094-32000-036-29
Nonfunded Cooperative Agreement
Start Date: Dec 01, 2010
End Date: Nov 30, 2015
Emerging infectious diseases (EID) are a threat to global health. Socio-economic, environmental, and ecological factors are believed to drive that increasing health threat. Zoonoses represent the majority of recent EID events. During the last decade vector-borne diseases were shown to comprise 28.8% of the EID events. Arthropods are important vectors of infectious agents pathogenic to humans, and domestic and wild animals. A systems biology approach offers the opportunity to develop effective interventions for the sustainable control of arthropod-borne diseases. Such approach requires the collection and analysis of comprehensive data sets, which enables the integration of components comprising biological systems.
The effects of specific mutations in Borrelia genes that affect disease transmission in a needle inoculation system mouse model will be compared to molecular events occurring during natural infection through the bite of Borrelia-infected Ixodes scapularis. ARS will supply uninfected I. scapularis ticks and expertise on tick biology, while UTSA will conduct the disease transmission studies using mutant strains of Borrelia burgdorferi and evaluate the mutant strain's ability to transmit the disease from infected tick to mouse.
Another objective involves the exploration of phenotypic and genotypic changes on the tick's ability to acquire a blood meal according to its infection status.
The discovery and development of safer acaricides with novel modes of action remains an unmet need. A unique chemical library will be screened for acaricidal activity as part of this collaboration.
ARS will establish a colony of Ixodes scapularis ticks and provide adult ticks, larvae, or eggs to cooperator at appropriate stages in the project.
ARS will provide advisory information on I. scapularis biology to guide the experimental design of RNAi experiments seeking to silence specific gene expression of genes that are under consideration as anti-Borrelia vaccine candidates.
Cooperator will provide USDA access to UTSA's chemical library for evaluating the toxicity of the small molecule chemicals to ticks (cattle fever tick, black legged tick, and lone star tick) and biting flies (horn fly, stable fly, and sand fly). UTSA and USDA cooperators will jointly select a group of compounds from the chemical library based on their structures, and UTSA will provide sufficient amount of each selected compound to USDA scientists. The USDA scientists will develop an appropriate bioassay method for each of the target arthropod species that can best utilize the materials. After the initial screening, promising molecules will be identified based on which other related compounds will be selected for the next round of screening.