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ARS Home » Plains Area » Kerrville, Texas » Knipling-Bushland U.S. Livestock Insects Research Laboratory » LAPRU » Research » Research Project #430846

Research Project: Towards Novel Acaricide Development Against Cattle Fever Tick: GPCR Target Validation and Identification of Chemical Leads

Location: Livestock Arthropod Pests Research

Project Number: 3094-32000-036-53-R
Project Type: Reimbursable Cooperative Agreement

Start Date: Feb 15, 2016
End Date: Feb 14, 2020

Objective:
Identify GPCRs that upon chemical intervention cause tick death or impair tick fitness and reproduction, contributing to tick control. This will identify the most promising novel acaricides (or acaricide leads), which will be tested on ticks in laboratory bioassays and on-cattle assays.

Approach:
1. Pharmacological profiling: the pharmacological profile of G protein-coupled receptors for biogenic amines (tyrosine, TYR; octopamine, OAR) and small neuropeptides that function in tick water balance and reproduction will be determined with endogenous and synthetic ligands. 2. Physiological target validation of receptors in #1 will be performed using RNAi. 3. Chemical target validation: Active synthetic molecules in #1 will be also used for chemical target validation in vivo to determine their utility as chemical leads. Assess target site activity of naturally occurring mono- and sesquiterpenoids on recombinant tick biogenic amine receptor(s) using a high-throughput screening system as in #1. Promising compounds identified will be tested in tick bioassays in the laboratory and with ticks on (infesting) cattle.