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Full-Text Articles in Physical Sciences and Mathematics

Dissecting Trypanosome Metabolism By Discovering Glycolytic Inhibitors, Drug Targets, And Glycosomal Ph Regulation, Daniel Hale Call May 2024

Dissecting Trypanosome Metabolism By Discovering Glycolytic Inhibitors, Drug Targets, And Glycosomal Ph Regulation, Daniel Hale Call

Theses and Dissertations

Trypanosoma brucei, the causative agent of African trypanosomiasis, and its relatives Trypanosoma cruzi and several Leishmania species belong to a class of protozoa called kinetoplastids that cause a significant health burden in tropical and semitropical countries across the world. While an improved therapy was recently approved for African trypanosomiasis, the therapies available to treat infections caused by T. cruzi and Leishmania spp. remain relatively poor. Improving our understanding of T. brucei metabolism can inform on metabolism of its relatives. The purpose of the research presented in this dissertation was to develop novel tools and methods to study metabolism in T. …


A Fret Flow Cytometry-Based Screening Assay For Multiplex Analysis Of Metabolites In T. Brucei, Ronald A. Zegarra Jun 2021

A Fret Flow Cytometry-Based Screening Assay For Multiplex Analysis Of Metabolites In T. Brucei, Ronald A. Zegarra

Undergraduate Honors Theses

Kinetoplastid parasites are a significant public health issue in some tropical and subtropical regions of the world. Kinetoplastid parasites all require glycolysis for survival, with host glucose key for ATP production. One such parasite, Trypanosoma brucei, exclusively metabolizes glucose in its bloodstream form. Trypanosomal glycolysis is unique because it displays unconventional structural features. Hence, glucose metabolism has been studied extensively in T. brucei and is a therapeutic target in kinetoplastid parasites.The lack of in vivo analytical techniques for measuring vital glycolytic metabolites in situ has restricted the ability of researchers to test, with high sensitivity and specificity, the essential roles …


Endocytosis As An Additional Mechanism Of Glucose Transport To The Hexose Transporter In Trypanosoma Brucei, Jongsu Choi Dec 2018

Endocytosis As An Additional Mechanism Of Glucose Transport To The Hexose Transporter In Trypanosoma Brucei, Jongsu Choi

Theses and Dissertations

Trypanosoma brucei is an extracellular kineotoplastid parasite that causes human African trypanosomiasis (HAT), also known as sleeping sickness. As trypanosomes undergo vector to host transition, heavy transcriptional adaptation such as metabolic shift to glycolysis and upregulated endocytosis occurs. Specifically, glycolysis in the infectious stage becomes the sole source of energy production; thus, the glucose transport mechanism in T. brucei provides one of the most promising therapeutic targets for development of new drugs to treat HAT. Despite an established trypanosome hexose transporter (THT) model for glucose transport across the plasma membrane, there remains gaps in the detailed mechanism of glucose transport …