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Grantee Research Project Results

NCER Grantee Research Project Results

Targeting an Octopamine Receptor From the Southern Cattle Tick (Rhipicephalus microplus) for Targets of Biopesticides

EPA Grant Number: FP917332
Title: Targeting an Octopamine Receptor From the Southern Cattle Tick (Rhipicephalus microplus) for Targets of Biopesticides
Investigators: Gross, Aaron D
Institution: Iowa State University
EPA Project Officer: Cobbs-Green, Gladys M.
Project Period: August 1, 2011 through July 31, 2014
Project Amount: $126,000
RFA: STAR Graduate Fellowships (2011)
Research Category: Academic Fellowships

Description:

Objective:

The southern cattle tick, which transmits the causative agents leading to Texas Cattle Fever, can result in significant economic losses to the cattle industry. The southern cattle tick resurgence has recently intensified, resulting in the need to identify safe and biorational control measures to aid in the integrated approach to controlling this tick. This research project will identify and investigate an octopamine receptor from the southern cattle tick for the development of botanical terpenoids as acaricides.

Approach:

Preliminary results have identified a putative octopamine receptor from the southern cattle tick, which has been validated to be a relevant acaricide target, and will serve as the basis for the first phase of the research performed. Functional response of the putative octopamine receptor will be accomplished by using a yeast histidineauxotrophic assay to confirm that this receptor responds to the putative ligand, octopamine. The yeast assay will create a high-throughput platform to screen libraries of potential compounds that interact with this receptor. Octopamine and lead compounds identified from the yeast assay will undergo a more rigorous investigation into the pharmacology of the putative octopamine receptor. This will generate new data on receptor pharmacology, specifically activation of downstream cellular processes (second messengers), that cannot be attained with the yeast histidineauxotrophic assay and will provide a higher level of scrutiny to receptor classification. The most important compounds identified with the cell expression assays will be tested against strains of ticks that are susceptible or resistant to synthetic acaricides.

Expected Results:

Use of biorational botanical compounds against insects and acarines has increased in the past several years. It has been proposed that natural compounds may provide several mechanisms of action, including interacting with octopamine receptors. Although the results that are expected to be obtained by performing this research will not solve the continued threat of the southern cattle tick, it is expected to augment the multiple approaches that are needed in an arsenal to combat resurgence of this economically important pest. This research is expected to identify an octopamine receptor from the southern cattle tick and describe the activation of second messenger systems. It also is expected that this research will identify a variety of terpenoids that interact with this putative octopamine receptor to some degree. Identified octopaminergic candidate compounds will be tested against ticks to investigate adverse physiological response(s) and/or death. Compounds that display octopamine receptor activity and lethality can be used to generate quantitative structure-activity relationships (QSARs) that can be utilized to identify additional effective compounds based on unique physicochemical properties. Generation of new information about the pharmacology of the tick’s octopaminergic system will be a significant advance in the understanding of acarine neurobiology. This research also may assist in controlling the spread of these ticks not only in the United States but also in Mexico, Central America and South America where this tick has significant impact.

Potential to Further Environmental/ Human Health Protection

Currently and previously used conventional insecticides can have significant adverse impacts on human health and the environment, including non-target wildlife. The movement towards biorational compounds may decrease the negative impacts on the environment and decrease public concern over the safety of currently used products.

Supplemental Keywords:

octopamine, octopamine receptor, GPCR, southern cattle tick, Texas cattle fever, terpenoids, essential oils, biorational, biopesticides

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The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.

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