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Biochemistry, Biophysics, and Structural Biology Commons™
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Articles 1 - 10 of 10
Full-Text Articles in Biochemistry, Biophysics, and Structural Biology
Vitamin D Regulates Metabolic Gene Expression, Glutamate And Glutamine Utilization, And Mitochondrial Function In Human Mammary Epithelial Cells, Sarah Beaudin
Legacy Theses & Dissertations (2009 - 2024)
Exposure to 1,25-Dihydroxyvitamin D (1,25D) decreases proliferation and induces differentiation in telomerase-immortalized human mammary epithelial (hTERT-HME1) cells. The studies described here addressed the mechanisms by which these effects are exerted. Microarray experiments were used to identify a subset of metabolic genes and pathways that are altered by 1,25D. In particular, genes involved in glutamate and glutamine utilization, including SLC1A1 and GLUL, were studied. Interestingly, qPCR analysis in a panel of six cell lines, representing either normal epithelial tissue or breast cancer, demonstrated diverse gene expression responses to 1,25D. In an isogenic model of mammary cell transformation, 1,25D altered gene expression …
Genome-Scale Analyses Of Transcription And Transcriptional Regulation In Bacteria, Devon Marie Fitzgerald
Genome-Scale Analyses Of Transcription And Transcriptional Regulation In Bacteria, Devon Marie Fitzgerald
Legacy Theses & Dissertations (2009 - 2024)
The textbook model of bacterial transcription regulation posits that promoters occur immediately upstream of genes and that transcription factors (TFs) modulate transcription through promoter-proximal binding. However, the recent application of unbiased genome-wide approaches, such as ChIP-seq and RNA-seq, has revealed a much more complex picture, including TF binding and transcription initiation occurring in unexpected locations. This dissertation describes the use of deep sequencing-based approaches to evaluate the genome-wide binding of transcription-related proteins and identify locations of transcription initiation. I have assessed the genome-wide binding of three Escherichia coli TFs and an alternative σ factor. Additionally, I have analyzed genome-wide patterns …
Francisella Tularensis Catalase Restricts Immune Function By Impairing Trpm2 Channel Activity, Nicole Lynn Flaherty
Francisella Tularensis Catalase Restricts Immune Function By Impairing Trpm2 Channel Activity, Nicole Lynn Flaherty
Legacy Theses & Dissertations (2009 - 2024)
As an innate defense mechanism, macrophages produce reactive species that weaken pathogens and serve as secondary messengers to modify signaling responses involved in immune function. The gram-negative bacterium F. tularensis utilizes its antioxidant armature to limit the host immune response but the mechanism behind this suppression has not been defined. Here we establish that F. tularensis limits Ca2+ entry thereby limiting actin reorganization and IL-6 production in a redox-dependent fashion. Wild-type (LVS) or catalase deficient F. tularensis (∆katG) show distinct profiles in their H2O2 scavenging capacity, 1 pM/sec and 0.015 pM/sec, respectively. Murine alveolar macrophages infected with ∆katG display distinct …
Myoepithelial Cell Morphogenesis And Differentiation In The Mouse Submandibular Salivary Gland In Development And Disease, Elise Marie Gervais
Myoepithelial Cell Morphogenesis And Differentiation In The Mouse Submandibular Salivary Gland In Development And Disease, Elise Marie Gervais
Legacy Theses & Dissertations (2009 - 2024)
Organogenesis is the process by which tissues organize, gain considerable size, and undergo cellular differentiation or specialization to form fully functional organs. To study the processes involved in organogenesis of branched organs, the mouse submandibular salivary gland is frequently used as a model system, as it can undergo morphogenesis and differentiation and be genetically manipulated ex vivo. The mouse submandibular salivary gland undergoes a specific process of outgrowth and invagination known as branching morphogenesis which allows for the significant increase in gland size and complexity, as well as maximization of surface area for secretion of saliva. Surrounding the mouse submandibular …
Novel Nmr Based Technologies To Study Macromolecular Structures, Subhabrata Majumder
Novel Nmr Based Technologies To Study Macromolecular Structures, Subhabrata Majumder
Legacy Theses & Dissertations (2009 - 2024)
Nuclear Magnetic Resonance Spectroscopy (NMR) is one of the principle tools in structural biology to probe macromolecular structures and interactions. The atomic resolution afforded by this technique has been widely used to probe protein-protein, and protein-ligand interactions in-vitro. However, the natural milieu of the proteins is the living cell and the cellular cytoplasm is extremely heterogeneous. The NMR studies of folded protein in-cell, till now, have been limited by non-specific interactions of the cytosol. This thesis outlays a general methodology to study protein structure/interactions inside the living cells using NMR. In a closely related objective, it also describes the use …
Using A Novel Multiplexing Method To Track Cell Populations And Cytodifferentiation During Development Of The Submandibular Salivary Gland, Charles Thomas Manhardt
Using A Novel Multiplexing Method To Track Cell Populations And Cytodifferentiation During Development Of The Submandibular Salivary Gland, Charles Thomas Manhardt
Legacy Theses & Dissertations (2009 - 2024)
The development of submandibular salivary glands is complex and requires coordination of specific signaling events. Submandibular salivary glands originate as an epithelial invagination into the adjacent mesenchyme that leads to a single stalk and end bud; this end bud will go through a clefting process. Numerous rounds of clefting will lead to a fully developed salivary gland by this process, which is known as branching morphogenesis. As the gland undergoes morphogenesis, specific cues leading to differentiation of multiple cell types and even epithelial sub classes are required. By the later stages of development the glands are fully innervated, have an …
Rna Aptamers For Molecular Chaperones Hsp27 And Hsp90, Sathishkumar Kumar Munusamy
Rna Aptamers For Molecular Chaperones Hsp27 And Hsp90, Sathishkumar Kumar Munusamy
Legacy Theses & Dissertations (2009 - 2024)
Hsp90 and Hsp27 are members of the heat shock protein family of chaperones that perform multiple roles in cellular maintenance through protein folding and inhibition of apoptosis. They are abundantly expressed in cells and are over-expressed during conditions of stress. Hsp90 requires ATP for its chaperone function while Hsp27 self-associates into higher order oligomers enclosing its substrate. Their ability to interact with other proteins or with themselves lies at the heart of their mechanisms. The specific consequences of each of their interactions on global cellular health have not yet been fully discovered. The sheer diversity of proteins that interact with …
Rna Aptamer Mediated Manipulation Of The 70 Kilodalton Heat Shock Protein Chaperone Machinery, Deepak Thirunavukarasu
Rna Aptamer Mediated Manipulation Of The 70 Kilodalton Heat Shock Protein Chaperone Machinery, Deepak Thirunavukarasu
Legacy Theses & Dissertations (2009 - 2024)
Protein quality control involves refolding of damaged proteins and facilitating degradation of irreparable proteins. Understanding the protein quality control mechanism is critical, since defects in it has been implicated in a number of age-related diseases like neurodegenerative diseases and also in cancer. A vast network of molecular chaperones and proteolytic systems collaborate to maintain protein quality control. The 70 kilodalton Heat shock protein (Hsp70) is a highly conserved and ubiquitous chaperone, which interacts with a variety of protein substrates including newly synthesized polypeptides, unfolded, partially misfolded and native proteins to maintain protein quality control. Hsp70 chaperone function is coupled to …
The Structural Heterogeneity And Dynamics Of Base Stacking And Unstacking In Nucleic Acids, Ada Anna Sedova
The Structural Heterogeneity And Dynamics Of Base Stacking And Unstacking In Nucleic Acids, Ada Anna Sedova
Legacy Theses & Dissertations (2009 - 2024)
Base stacking provides stability to nucleic acid duplexes, and base unstacking is involved in numerous biological functions related to nucleic acids, including replication, repair, transcription, and translation. The patterns of base stacking and unstacking in available nucleic acid crystal structures were classified after separation into their individual single strand dinucleotide components and clustering using a k-means-based ensemble clustering method. The A- and B-form proximity of these dinucleotide structures were assessed to discover that RNA dinucleotides can approach B-form-like structures. Umbrella sampling molecular dynamics simulations were used to obtain the potential of mean force profiles for base unstacking at 5'-termini for …
Structure And Stability Of Amyloid Fibrils Studied By Advanced Vibrational Spectroscopy, Marudachalam Shanmugasundaram
Structure And Stability Of Amyloid Fibrils Studied By Advanced Vibrational Spectroscopy, Marudachalam Shanmugasundaram
Legacy Theses & Dissertations (2009 - 2024)
Protein misfolding often leads to the formation of refractory protein aggregates like amyloid fibrils. These fibrils possess a highly ordered structure and are implicated in over 25 severe diseases including Alzheimer’s, Parkinson’s and prion diseases. This work was focused on understanding the morphology and conformation of amyloid fibrils and their stability after formation. The deconstruction of fibrils as well as other aggregates like inclusion bodies under mild conditions was also investigated using Archaeal chaperones.