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Full-Text Articles in Biochemistry
Characterization Of The Effects Of The Pyrazolopyrimidine Inhibitor Grassofermata (Nav-2729) In The Eukaryotic Pathogen Trypanosoma Brucei, Kristina Marie Parman
Characterization Of The Effects Of The Pyrazolopyrimidine Inhibitor Grassofermata (Nav-2729) In The Eukaryotic Pathogen Trypanosoma Brucei, Kristina Marie Parman
All Dissertations
The protozoan pathogen, Trypanosoma brucei, is the causative agent of sleeping sickness in humans and nagana in livestock in sub-Saharan Africa. T. brucei cycles between tsetse fly and mammalian hosts, and it is adapted to survive in diverse host tissues. Variant Surface Glycoprotein (VSG) plays a key role in immune evasion in the mammalian host. The VSG membrane anchor requires two myristates, 14-carbon saturated fatty acids (FAs) that are scarce in the host. T. brucei can synthesize FAs de novo, but also readily takes up exogenous FAs, despite lacking homologs to fatty acid uptake proteins found in other …
Fatty Acids And Parasitism: Towards A Better Understanding Of Lipid Metabolism In Trypanosoma Brucei, Joshua Saliutama
Fatty Acids And Parasitism: Towards A Better Understanding Of Lipid Metabolism In Trypanosoma Brucei, Joshua Saliutama
All Dissertations
Trypanosoma brucei is an extracellular eukaryotic parasite that causes sleeping sickness in humans and cattle. As an extracellular parasite, T. brucei relies on the host’s nutrients to satisfy its growth requirements. The parasite is unusual because it does not uptake most of the host’s lipid species. Instead, T. brucei prefers to perform de novo synthesis of most lipid species. One of the lipid species that T. brucei can both uptake and synthesize is fatty acids. In my thesis work, I investigated the dynamics of fatty acid uptake, metabolism, and utilization of T. brucei. My work starts by determining the …
Mechanisms Of Telomere Maintenance In Trypanosoma Brucei, M A G G. Rabbani
Mechanisms Of Telomere Maintenance In Trypanosoma Brucei, M A G G. Rabbani
ETD Archive
Telomeres are a nucleoprotein structure at the end of the chromosome and are essential for genome integrity and chromosome stability. Telomere lengths are primarily maintained by a telomerase-mediated pathway but can be maintained by a homologous recombination-mediated pathway. However, detailed mechanisms of telomere maintenance are still unclear in many eukaryotes, including an important human pathogen, Trypanosoma brucei. Telomeres can be elongated by telomerase in T. brucei, a causative agent of fatal sleeping sickness in humans and nagana in cattle. T. brucei evades host immune response by regularly switching its major surface antigen, variant surface glycoprotein (VSG), a process known as …
Characterization Of A Potential Glucose Transporter In Trypanosoma Brucei, Matthew Morgan
Characterization Of A Potential Glucose Transporter In Trypanosoma Brucei, Matthew Morgan
All Theses
Trypanosoma brucei, the African trypanosome, is an organism heavily dependent on glucose for ATP production during the infectious stage of its life cycle. Here, we have explored the role of an uncharacterized protein designated “novel glucose transporter” (NGT) as a potential glucose transporter. Sequence analyses suggests that NGT shares similarities (either at the primary sequence level or structurally) with Trypanosome Hexose Transporters 1 (TbTHT1), and human GLUT3, both of which are membrane sugar transporters. NGT was localized by fluorescence microscopy to subcellular structures consistent with lysosomes. Silencing NGT expression with RNA interference in parasites resulted in a growth defect …
A Fret Flow Cytometry-Based Screening Assay For Multiplex Analysis Of Metabolites In T. Brucei, Ronald A. Zegarra
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 …
Innate Antibodies, Murine Models, And Evolution: A Study Of Trypanosome Lytic Factor Functions And Their Translational Applications, Joseph P. Verdi
Innate Antibodies, Murine Models, And Evolution: A Study Of Trypanosome Lytic Factor Functions And Their Translational Applications, Joseph P. Verdi
Dissertations, Theses, and Capstone Projects
Trypanosome lytic factors (TLFs) are primate-specific antimicrobial protein complexes that lyse African trypanosome parasites by delivering the channel-forming toxin APOL1 to the invading microorganisms. Human serum contains two TLFs that are delivered to the parasite by separate mechanisms, only one of which has been characterized. TLF1 is endocytosed by a receptor that is typically blocked by other serum factors in vivo, suggesting that TLF2 is the more relevant lytic factor in the context of trypanosome immunity. TLF2 is non-covalently associated with polyclonal immunoglobulin M (IgM) antibodies, which we report here to be involved in the uptake mechanism. The TLF2-IgMs …
Regulation Of Trypanosoma Brucei Hexokinase 1 And 2 On Multiple Levels: Transcript Abundance, Protein Expression And Enzyme Activity, Heidi Dodson
All Dissertations
Trypanosoma brucei, a unicellular eukaryotic parasite, is the causative agent of African sleeping sickness in sub-Saharan Africa. The parasite encounters two main environments as it progresses through its life cycle: the tsetse fly and the mammalian
bloodstream. Nutrient availability is distinct in the two environments, requiring the parasite to utilize diverse metabolic pathways to efficiently produce ATP for survival. Bloodstream form parasites (BSF), residing in a glucose rich environment, rely solely on
glycolysis for energy, while procyclic form (PF) parasites metabolize readily available proline and threonine in addition to glucose.
T. brucei expresses two hexokinases, the first enzyme in the …