2012 Annual Report 1a.Objectives (from AD-416): Establish mutually productive collaboration to discover and develop target-specific pesticides to control parasitic arthropods impacting animal and public health. 1b.Approach (from AD-416): We will provide enzymatically active recombinant acetylcholinesterases from several economically important pests, beginning with rBmAChE1, the major acetylcholinesterase (AChE) of Rhipicephalus (Boophilus) microplus, and following with AChEs from other pest species, including sand flies, ticks, and biting flies. Cooperator will screen various ligands for specific binding to the AChEs that result in blocking the enzymatic activity. It is also possible that other binding sites may result in pesticidal activity without blocking enzymatic activity. Candidate control ligands will, in turn, be provided to KBUSLIRL scientists for in vivo and in vitro screening to test control efficacy against target pests. 3.Progress Report: Computer modeling resulted in an improved model of the acetylcholinesterase enzyme structure being developed. Using this information new enzyme inhibitors have been identified that are more specific for the tick form of acetylcholinesterase compared to mammalian acetylcholinesterase. Thus, it is expected these new inhibitors will have reduced toxicity to humans and cattle.