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Analysis Of Zinc Transporters In C. Elegans, Hyun Cheol Roh
Analysis Of Zinc Transporters In C. Elegans, Hyun Cheol Roh
All Theses and Dissertations (ETDs)
Zinc is a trace element essential for organisms, and organisms have homeostatic mechanisms to control zinc metabolism. Zinc metabolism is mediated by numerous proteins including zinc transporters, zinc-responsive transcription factors and zinc-binding proteins. Of these proteins, zinc transporters, composed of CDF and ZIP families, play a major role and are implicated in a variety of human diseases. However, the mechanisms by which zinc transporters coordinate to regulate zinc homeostasis in whole animals and by which they are related to human diseases are not well understood. To address these questions, we used C. elegans as a model system. While three C. …
Targeting And Activity Of The Aaa+ Atpase Torsina Within The Endoplasmic Reticulum, Abigail Vander Heyden
Targeting And Activity Of The Aaa+ Atpase Torsina Within The Endoplasmic Reticulum, Abigail Vander Heyden
All Theses and Dissertations (ETDs)
AAA+ ATPase enzymes couple ATP hydrolysis to the exertion of conformational change on a substrate. TorsinA is one of the few AAA+ ATPases that resides within the lumen of the mammalian endoplasmic reticulum: ER). A glutamic acid deletion in the catalytic domain of torsinA causes DYT1 dystonia, but torsinA's function and the basis for disease remain unclear. I show that torsinA is dynamically targeted from the bulk ER to nuclear envelope: NE) upon coexpression with a cofactor protein, LULL1, and that torsinA's movement into the NE is concomitant with displacement of select linker of the nucleoskeleton and cytoskeleton: LINC) complex …
The Functions Of Autophagy Genes In Lymphocytes And Osteoclasts, Brian Miller
The Functions Of Autophagy Genes In Lymphocytes And Osteoclasts, Brian Miller
All Theses and Dissertations (ETDs)
Macroautophagy: herein autophagy) is a process by which cells degrade long-lived proteins and organelles. The autophagy pathway and autophagy genes have been implicated in many functions in the cell such as protecting against metabolic stress, degrading damaged organelles, and regulating vesicular trafficking. To study the role of autophagy in primary cells with important physiologic functions, we generated mice lacking essential autophagy genes in B lymphocytes, T lymphocytes, and osteoclasts. We found that the essential autophagy gene Atg5 was important for B cell development and for the maintenance of B-1a B cell numbers but not peripheral B-2 B cell numbers. In …
The Role Of Ikkβ In Osteoclastogenesis And Inflammatory Osteolysis, Jesse Otero
The Role Of Ikkβ In Osteoclastogenesis And Inflammatory Osteolysis, Jesse Otero
All Theses and Dissertations (ETDs)
Bone homeostasis is essential for health and is altered in many pathological conditions. A balance in the activity of osteoblasts: bone-building cells) and osteoclasts: boneresorbing cells) determines the state of bone metabolism, and a tip in this balance toward either cell type is detrimental to health. In clinical settings, the most common bone diseases favor increased osteoclast activity and include osteoporosis and rheumatoid arthritis. Heightened osteoclast differentiation and activation in these conditions causes bone loss which results in increased fracture risk, bone pain, and deformity. Understanding the mechanisms by which osteoclasts develop will elucidate important targets for therapy in these …
Opposing Crosstalk Between Rho1 And Cdc42 In Epithelial Morphogenesis, Steve Warner
Opposing Crosstalk Between Rho1 And Cdc42 In Epithelial Morphogenesis, Steve Warner
All Theses and Dissertations (ETDs)
Epithelial cells line all surfaces of the body exposed to external environments where they perform critical roles for maintaining homeostasis. In addition, epithelial cells are implicated in several disease processes and are the most common cell type implicated in cancer. Therefore, understanding the regulation of epithelial cell development and function has important implications for adult homeostasis and disease states. The Rho family of small GTPases functions in a wide array of cellular processes in epithelial cells. However, in mammals Rho subfamilies have multiple members, often with overlapping roles, complicating the precise determination of Rho protein function in epithelial cells, especially …
A Molecular Basis For Divergent, Unstable Actin Filaments In Toxoplasma Gondii, Kristen Skillman
A Molecular Basis For Divergent, Unstable Actin Filaments In Toxoplasma Gondii, Kristen Skillman
All Theses and Dissertations (ETDs)
Toxoplasma gondii is an important parasitic pathogen of the phylum Apicomplexa. Parasite invasion of host cells involves a unique gliding motility mechanism that is dependent on polymerization of parasite actin. However, in non-motile parasites, the majority of actin is monomeric and filaments only assemble upon initiation of gliding motility. Actin filament turnover is crucial for motility as shown by the detrimental effects of jasplakinolide, an agent that stabilizes actin filaments. T. gondii actin: TgACTI) is functionally highly divergent from conventional actin and only polymerizes into very short filaments. To understand why T. gondii actin does not form long filaments and …
Genetic And Chemical Genetic Approaches To Shiga Toxin Inhibition, Jose Saenz
Genetic And Chemical Genetic Approaches To Shiga Toxin Inhibition, Jose Saenz
All Theses and Dissertations (ETDs)
Infection with Shiga toxin-producing bacteria can place patients at risk of developing hemolytic uremic syndrome, a toxemic condition characterized by hemolytic anemia, thrombocytopenia, and acute renal failure. Though hemolytic uremic syndrome remains the leading cause of acute renal failure in children under the age of 5, treatment of this disease remains purely supportive. In order to limit the systemic effects of Shiga toxin, efforts must be undertaken to target intoxicated cells. To this end, we have focused on two aspects of Shiga toxin pathogenesis. One approach relied on a high-throughput screen of a small compound library to identify potential inhibitors …
Enzymology Of Dhhc-Mediated Protein S-Acylation, Benjamin Jennings
Enzymology Of Dhhc-Mediated Protein S-Acylation, Benjamin Jennings
All Theses and Dissertations (ETDs)
Protein S-acylation is the post-translational modification of proteins with long-chain fatty acids at cysteine residues via a thioester linkage. The most commonly attached lipid is 16-carbon palmitate, thus the process is often called palmitoylation. Unlike other lipid modifications, protein S-acylation is reversible. Consequently, cells use acylation/deacylation cycles to regulate protein localization, stability, and activity. A family of integral membrane enzymes called DHHC proteins because of a conserved Asp-His-His-Cys motif, catalyze protein S-acylation within cells. DHHC proteins have been associated with human diseases including cancers, Huntington's disease, and mental retardation. However little is known about their function or regulation. This work …