Creation of a biotechnology discovery platform for fighting the transmission of vector-borne infectious diseases
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Vector-borne diseases have become a global pandemic threatening 40% of the world's population with infectious diseases like malaria and Lyme disease becoming ever more of a concern. The best treatment of vector-borne diseases is to prevent their transmission through the usage of personal protective measures (PPMs). However, mosquitoes and ticks are becoming resistant to common PPMs, including DEET, and this demands development of next generation deterrents with new mechanisms of action. The octopamine receptor (OctR) is an attractive target for next generation deterrent development because it is invertebrate specific and plays an important role in fine motor control. In this study, Anopheles gambiae OctRs and Ixodes scapularis OctRs were cloned into HEK293 cells followed by characterization of these receptors with agonist/antagonist pharmacological profiles. Further Structure-Activity Relationships (SAR) of octopamine-like compounds and novel series compounds to the receptor were assessed. SAR assessments would be helpful to design new OctRs ligands that are highly selective for the OctRs over mammalian off-targets. By associating in vitro biting assay results with agonist profiles of the OctRs, a new biotechnology platform is being tested. Using these methodologies we plan to address the growing concern of vector-borne diseases by discovering mechanistically new PPMs. As part of this initiative, the biotechnology platform we developed will provide a rapid way to identify potential next generation deterrents by exploring the structure-activity relationship of novel compounds on octopamine receptors from disease-transmitting arthropod species.