Abstract by Matt Hyer
Chemistry and Biochemistry
Developing fluorescent biosensors to investigate how intraglycosomal pH affects regulation of glycolysis in BF trypanosoma brucei
Human African Trypanosomiasis (HAT) is a fatal disease caused by Trypanosoma brucei that affects many in sub-Saharan Africa. Bloodstream form (BF) T. brucei only metabolize glycolysis and most glycolytic enzymes are compartmentalized within a peroxisome-like organelle called the glycosome. This makes the study and possible drug targeting of the glycosome and therefore the glycolytic enzymes a promising strategy for treating HAT. The chemical pH reporter we previously used in PCF parasites does not function in BF parasites. Hence, we have targeted genetically encoded fluorescent protein pH sensors to the glycosome by appending a peroxisomal targeting sequence to the fluorescent protein. With this tool we are developing, we can determine whether similar mechanisms are operating in BF to regulate glycolysis, which is the more physiologically relevant form of the parasite. We report initial results using pHRed and a newer, brighter SypHer3s for making pH measurements in BF glycosomes.