Program Director/Principal Investigator (Last, First, Middle): Morris, James, Culvin Project Summary/Abstract Members of the class Kinetoplastea, which includes the African trypanosome Trypanosoma brucei and Leishmania spp., place a tremendous burden on human health with an estimated ~1.4 million cases of disease recorded in 2015 (World Health Organization). Glucose metabolism is critical to the success of these parasites, suggesting that inhibition of glucose uptake and sub-cellular distribution in these parasites would be effective means of control. The goal of this application is to use fluorescence-based glucose probes in live parasites to identify inhibitors of (a.) environmental glucose uptake and (b.) organellar glucose uptake. We will systematically confirm the inhibitory activity of primary hits using a series of secondary confirmation assays with hits being scored for anti-parasitic activity. Through an iterative approach that weighs activity against glucose uptake and parasite viability, scaffolds will be identified that are potent inhibitors of glucose uptake with promising broad-spectrum anti-kinetoplastid activity. PHS 398/2590 (Rev. 06/09) Page 1 Continuation Format Page
Morris, James, Culvin Project Narrative The proposed research is important to public health as identification of novel inhibitors of kinetoplastid parastie glucose uptake and distribution will serve as the first step in the development of desperately needed new therapeutics for diseases like African sleeping sickness and visceral leishmaniasis, maladies that devastate communities throughout the world. PHS 398/2590 (Rev. 06/09) Page 1 Continuation Format Page
| Voyton, Charles M; Morris, Meredith T; Ackroyd, P Christine et al. (2018) FRET Flow Cytometry-Based High Throughput Screening Assay To Identify Disrupters of Glucose Levels in Trypanosoma brucei. ACS Infect Dis 4:1058-1066 |
| Voyton, Charles M; Qiu, Yijian; Morris, Meredith T et al. (2018) A FRET flow cytometry method for monitoring cytosolic and glycosomal glucose in living kinetoplastid parasites. PLoS Negl Trop Dis 12:e0006523 |
