Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 84 for “"proteostasis"”.
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Type I collagen proteostasis
… debated, but what is clear is that collagen proteostasis is strongly disrupted. In this thesis, I report a series of studies targeted at elucidating mechanisms of proteostasis for collagen type-1, the most abundant collagen in the human body. First, I explore the folding and assembly of the …
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The C-Propeptide in Collagen Proteostasis
… collagen assembly is well accepted, its role in proteostasis has only recently been appreciated. In Chapter 2, we demonstrate that the highly-conserved N-glycan in the collagen-I C-Pro domain is critical for maintaining collagen proteostasis under challenging conditions. Specifically, the …
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Protein Folding, Host Cell Proteostasis, and Viral Evolution
… chaperones and quality control factors, termed proteostasis networks. When a substitution on a protein impedes its proper folding, proteostasis network components can triage the defective protein variant to chaperones for folding assistance, or to quality control factors for timely degradation. …
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Thiol-Based Misfolding: Linking Redox Balance to Cytosolic Proteostasis
… mechanism and model for redox-associated proteostasis.</p>
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Leveraging HSF1 chemical-genetic tools to elucidate mechanisms of proteostasis
… trafficking mechanisms collectively termed the proteostasis network. This network assists folding and maintains optimal protein localization and concentration. While the components and organization of this network are generally well-established, our understanding of how protein folding problems …
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New Roles for the Integrated Stress Response in Cancer and Proteostasis
… early in tumorigenesis, but also promoted proteostasis in response to the chemotherapy and proteasome inhibitor, bortezomib. We found this second finding to be mechanistically linked to a previously-undescribed role for the ISR in regulating the microtubule cytoskeleton to promote the …
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Amyloid β Aggregation is Coupled to Cellular Metabolism and Intramitochondrial Proteostasis
… the direct effort of intramitochondrial proteostasis on Aβ42 aggregation by performing a range of pharmacological assays. Overall, this work demonstrates a two-way association between Aβ42 self-assembly and mitochondrial function and proposes mitochondrial transplantation as a novel …
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A Role for PI31-Mediated Proteasome Regulation in Proteostasis and Neuronal Health
<p>The specific and timely degradation of proteins is achieved by the Ubiquitin-Proteasome System (UPS), which governs a variety of cellular processes such as apoptosis, cell cycle progression, protein quality control, and metabolism. Using this system, cells maintain homeostasis by quickly and …
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Epitranscriptomics : translational regulation of metabolism, drug resistance and proteostasis during cellular stress
The epitranscriptome -- the naturally occurring system of chemical modifications on ribonucleic acid (RNA) --
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Distant chaperones and N-glycan signals : new mechanisms of secretory pathway proteostasis
… new mechanisms for maintaining secretory pathway proteostasis.
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Respiratory chain deficiency alters cellular proteostasis and triggers Alzheimer’s disease-like tau alterations
… suggest mitochondrial function affects cellular proteostasis pathways including the mitochondrial unfolded protein response (mtUPR), integrated stress response (ISR), autophagy/mitophagy, and proteasome function. Although initial studies in C. elegans and rat hepatoma cells established a link …
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Defining the Influence of Host Cell Proteostasis Networks and Temperature on Influenza Evolution
… fold, and degrade their proteins. These proteostasis machineries can influence the accessible sequence landscape of viral proteins, and thus shape their evolution. Furthermore, the entire viral replication cycle takes place within the host cell. Therefore, the environment of the host, …
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Unveiling the Intercompartmental Signaling Axis: Mitochondrial to ER Stress Response (MERSR) and Its Impact on Proteostasis
… activated by the perturbation of mitochondrial proteostasis, which ultimately results in the improvement of proteostasis in the cytosol. Here, we found that this signaling axis also influences the unfolded protein response of the endoplasmic reticulum (UPRER), suggesting the presence of a …
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Methods to study protein folding and evolution in vivo
… factors which maintain protein homeostasis (proteostasis) by actively monitoring protein folding processes in an organelle-specific and dealing with protein misfolding in a stress-responsive manner. While we know that these "proteostasis networks" are capable of influencing protein folding, …
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Leveraging Protein Homeostasis as a Disease-modifying Strategy
Protein homeostasis (proteostasis) is a fundamental determinant of cellular health, and its impairment is causally linked to a wide range of human diseases. While extensive eHort has gone into characterising how the proteostasis network (PN) maintains proteins in their functional states, more work …
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Investigating dysregulation in protein quality control mechanisms in senescent cells
Loss of proteostasis and cellular senescence are both considered major hallmarks of ageing, and contribute to the development and maintenance of diseases of ageing. Cellular senescence enacts a programme of stable cell-cycle arrest, accompanied by profound alterations in cellular function including …
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Chaperoning viral protein evolution
… has focused on determining whether and how host proteostasis machinery modulates viral protein evolution. First, I employed a serial passaging approach to evolve influenza in host cells with remodeled proteostasis capacities, revealing that cytosolic host proteostasis capacity is indeed a …
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Investigating the role of the Caenorhabditis elegans unfolded protein response in immunity and development
… the endoplasmic reticulum (ER). To maintain ER proteostasis, the rate of nascent peptide influx into the ER must be matched with the rate of protein folding and export. An imbalance between peptide influx and ER folding capacity activates a conserved set of signal transduction pathways termed …
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Genetic analysis of endoplasmic reticulum homeostasis during stress and infection of Caenorhabditis elegans
… sensitizes animals to perturbations in cytosolic proteostasis. My results suggest that loss of fkh-9 enhances translocation of misfolded proteins out of the ER, thereby disrupting cytosolic proteostasis and decreasing proteasomal function. These findings implicate a critical need for balancing …
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Targeting proteostatic maintenance and mitochondrial function with phytochemical compounds in models of brain and skeletal muscle aging
… of sarcopenia and neurodegeneration are loss of proteostasis (protein homeostasis) and mitochondrial dysfunction. While progress has been made in understanding the etiology of chronic diseases, treatments for age-related chronic diseases affecting skeletal muscle and the brain are lacking. One …
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