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Full-Text Articles in Life Sciences

The Regulation Of Plasmodium Falciparum Metabolism By Haloacid Dehalogenase Proteins, Philip Frasse Aug 2021

The Regulation Of Plasmodium Falciparum Metabolism By Haloacid Dehalogenase Proteins, Philip Frasse

Arts & Sciences Electronic Theses and Dissertations

Malaria is an enormous financial and public health burden for much of the world, infecting over 200 million and killing over 400,000 people every year. While much progress has been made combating malaria in the past few decades, those advances have slowed in recent years, partially due to the emergence of resistance to all known antimalarials used to date. To achieve the goal of eliminating malaria as a major global health problem, new therapeutics need to be developed, targeting novel categories of parasite biology. One poorly understood area of parasite biology is the regulation of various metabolic pathways. We have …


Protein Synthesis Adaptation To The Au-Rich Transcriptome Of Plasmodium Falciparum, Jessey Lee Erath Jan 2021

Protein Synthesis Adaptation To The Au-Rich Transcriptome Of Plasmodium Falciparum, Jessey Lee Erath

Arts & Sciences Electronic Theses and Dissertations

The process of protein synthesis whereby a messenger RNA is decoded into an amino acid chainis conserved among the domains. Fastidious protein synthesis is necessary for organism survival. However, exceptions negatively affecting the mRNA translation cycle – inadvertently or by design – may occur. Polyadenosine tracts are one such motif causing ribosomal stalling and frameshifting in almost all organisms tested thus far; save Plasmodium spp. Thus, with ~60% of their protein-coding genome harboring polyadenosine tracts, the elucidation of such paradigm-breaking adaptations enabling Plasmodium spp. to translate this typically problematic motif without issue is salient from both basic science and clinical …


Breath Biomarkers And An Expanded Role For Isoprenoids In Plasmodium Falciparum, Chad Louis Schaber Aug 2018

Breath Biomarkers And An Expanded Role For Isoprenoids In Plasmodium Falciparum, Chad Louis Schaber

Arts & Sciences Electronic Theses and Dissertations

Malaria remains one of the deadliest infectious diseases worldwide, and efforts to combat it require novel insights into diagnostics, vector transmission, and drug inhibitor targets. Previous studies suggest that malaria infection causes hosts to preferentially attract the transmission vector, the Anopheles mosquito, but the mechanism and wider implication of these findings were not known. By analyzing the headspace above malaria parasite cultures, we identified several molecules that might engender mosquito attraction. We demonstrated that several of these molecules activate mosquito odorant receptors, including the known plant-emitted mosquito attractant _-pinene. During patient studies involving two independent pediatric clinical populations from Malawi, …


Robust Odorant Recognition In Biological And Artificial Olfaction, Nalin Katta Aug 2017

Robust Odorant Recognition In Biological And Artificial Olfaction, Nalin Katta

McKelvey School of Engineering Theses & Dissertations

Accurate detection and identification of gases pose a number of challenges for chemical sensory systems. The stimulus space is enormous; volatile compounds vary in size, charge, functional groups, and isomerization among others. Furthermore, variability arises from intrinsic (poisoning of the sensors or degradation due to aging) and extrinsic (environmental: humidity, temperature, flow patterns) sources. Nonetheless, biological olfactory systems have been refined over time to overcome these challenges. The main objective of this work is to understand how the biological olfactory system deals with these challenges, and translate them to artificial olfaction to achieve comparable capabilities. In particular, this thesis focuses …


Discovery And Characterization Of A Novel Class Of Metabolic Regulators In The Malaria Parasite Plasmodium Falciparum, Ann Marie Guggisberg Dec 2016

Discovery And Characterization Of A Novel Class Of Metabolic Regulators In The Malaria Parasite Plasmodium Falciparum, Ann Marie Guggisberg

Arts & Sciences Electronic Theses and Dissertations

The malaria parasite, Plasmodium falciparum, infects hundreds of millions of people per year and causes hundreds of thousands of deaths. Within the host red blood cell, the parasite relies on glycolysis for energy and synthesis of essential biomolecules. One such anabolic fate of glucose is the synthesis of isoprenoids, a broad and essential class of compounds that participate in a variety of cellular functions. In the face of ever-evolving drug resistance, new inhibitors and better understanding of parasite metabolism are required. The antibiotic fosmidomycin (FSM) targets the methylerythritol phosphate pathway for isoprenoid synthesis and is a well-validated inhibitor of P. …


Modulation Of Human And Malarial Glucose Transporter Activity By Lipids And Small Molecules, Thomas E. Kraft May 2016

Modulation Of Human And Malarial Glucose Transporter Activity By Lipids And Small Molecules, Thomas E. Kraft

Arts & Sciences Electronic Theses and Dissertations

Glucose transport is a fundamentally important process for maintenance and regulation of cellular metabolism in all kingdoms of life. Despite their high importance, detailed examination of glucose transport proteins in humans and parasites through biochemical, biophysical and structural properties was greatly hampered by the inability to express, purify and reconstitute sufficient amounts of active transporters. This dissertation describes strategies that led to the first successful expression, purification, stabilization and functional reconstitution of active insulin-responsive GLUT4 transport protein. Furthermore, the work described herein establishes a requirement of anionic and conical lipids for full activity of the mammalian glucose transporters GLUT3 and …


Molecular Mechanisms Of Plasmodium Red Blood Cell Invasion, Brian Michael Malpede May 2015

Molecular Mechanisms Of Plasmodium Red Blood Cell Invasion, Brian Michael Malpede

Arts & Sciences Electronic Theses and Dissertations

The malaria parasite Plasmodium utilizes specialized proteins for adherence to cellular receptors in its mosquito vector and human host. Adherence is critical for parasite development, host cell traversal and invasion, and protection from vector and host immune mechanisms. These vital roles have identified several adhesins as vaccine candidates. A deficiency in current adhesin-based vaccines is induction of antibodies targeting non-conserved, non-functional, and decoy epitopes due to the use of full length proteins or binding domains. To alleviate the elicitation of non-inhibitory antibodies, conserved functional regions of proteins must be identified and exploited. Structural biology provides the tools necessary to achieve …