This proposal will focus on further identification and characterization of host proteomic and genomic responses to malaria during the early stages of exposure and infection prior to the development of clinical symptoms. The in vivo study will be complemented by in vitro studies where early host responses during the pre-erythrocyte, hepatic and non-symptomatic stage of the disease will be fully characterized using combined proteomics and genomics technologies to accelerate the identification of blood biomarkers that will lead to highly accurate and sensitive diagnosis of early, asymptomatic malaria infection. We will use ProteinChip Surface Enhanced Laser Desorption and Ionization (SELDI) Time-of-Flight Mass Spectrometry (TOF-MS), Ultra Performance Liquid Chromatography (UPLC), and Affymetrix GeneChip microarrays to screen and identify early molecular markers predictive of malaria disease progression. This strategy can be easily automated to provide a rapid, sensitive and high throughput proteomic system to identify molecular signatures of malaria exposure. Selected candidate biomarkers in plasma/serum will be validated in a larger population, and will be assessed to determine their utility in prediction of malaria infection. Our goal is to develop a rapid, robust and portable diagnostic kit or biosensor based on the validated malaria biomarkers.
Keywords: Malaria, Infection, Exposure, Biomarkers, Proteomics, Genomics, Mass Spectrometry