Vector management has a proven track record in the control of insect-transmitted disease; unfortunately, the keystone of this control, insecticide treatment, is no longer effective in some areas due to development of resistance. However, there is limited incentive for pharmaceutical or agrochemical companies to develop new compounds to control the insect vectors of malaria and other neglected tropical diseases that disproportionately affect impoverished nations. Therefore, early-phase insecticide discovery of such compounds is a challenge that is primarily being borne by the non-profit sector. The team with expertise in arthropod genomics, vector biology, and insecticide-discovery and development has developed a robust insecticide discovery platform targeting G-Protein Coupled Receptors (GPCRs) in mosquitoes. GPCRs are de-orphanized by cloning and characterization in terms of ligand specificity and signaling cascades. Targets are prioritized by assessing their role in mosquito behavior using knock-down approaches. Expressed targets are screened against small molecule libraries to identify agonists and antagonists. Lead chemistries are further modified through medicinal chemistry to increase effectiveness and stability and decrease toxicity to humans. This strategy is constructed to identify mosquito adulticides, larvicides, and repellents.
While the research program is lab-based at the University of Notre Dame, the findings have implications for today's global health challenges.
Vector-borne disease research is a historic strength of the EIGH. Our researchers study multiple parts of the vector-borne disease lifecycle, such as how the parasites, viruses, and bacteria cause these kinds of diseases, how the vectors spread these diseases, and how to improve prevention methods in tropical and subtropical areas, which have the highest burden of vector-borne illnesses.
University of Notre Dame Partnerships
- Warren Family Research Center for Drug Discovery and Development
Kastner, K.W. , D.A. Shoue, G.L. Estiu, J. Wolford, M.F. Fuerst, L. D. Markley, J.A. Izaguirre and M.A. McDowell. Virtual Screening of the Anopheles gambiae Octopamine Receptor.