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Articles 1 - 12 of 12
Full-Text Articles in Molecular Biology
Regulation Of Gene Expression By Rna Binding Proteins And Micrornas, Kyle Cottrell
Regulation Of Gene Expression By Rna Binding Proteins And Micrornas, Kyle Cottrell
Arts & Sciences Electronic Theses and Dissertations
Regulation of gene expression is essential to life. Post-transcriptional regulation of gene expression is a complex process with many inputs that lead to changes in localization, translation and stability of mRNAs. The translation and stability of many mRNAs is regulated by cis-elements, such as mRNA-structure or codon optimality; and by trans-acting factors such as RBPs and miRNAs. Here I report on the complex interactions between RBPs, miRNAs and characteristics of their target mRNAs in respect to effects on translation and RNA stability.
Using a reporter based approach we studied modulation of microRNA-mediated repression by various mRNA characteristics. We observed the …
The Regulation Of Extracellular Amyloid-Β Levels By Ionotropic Glutamatergic Transmission In An Alzheimer’S Disease Mouse Model, Jane Cecelia Hettinger
The Regulation Of Extracellular Amyloid-Β Levels By Ionotropic Glutamatergic Transmission In An Alzheimer’S Disease Mouse Model, Jane Cecelia Hettinger
Arts & Sciences Electronic Theses and Dissertations
Brain extracellular concentration of the peptide amyloid-β (Aβ) is a major contributor to Alzheimer’s disease (AD) pathogenesis. High Aβ levels in the extracellular space precipitate aggregation of the peptide into soluble and insoluble toxic species. This process begins decades before cognitive impairment and triggers the cascade of pathology that eventually leads to AD. Synaptic activity is key to the regulation of extracellular Aβ levels. Presynaptic activity drives the production of Aβ, while postsynaptic receptor activation exhibits more nuanced regulation. For example, high levels of NMDA receptor (NMDA-R) activation have been shown to decrease Aβ production through the extracellular signal-regulated kinase …
Robust Algorithms For Detecting Hidden Structure In Biological Data, Roman Sloutsky
Robust Algorithms For Detecting Hidden Structure In Biological Data, Roman Sloutsky
Arts & Sciences Electronic Theses and Dissertations
Biological data, such as molecular abundance measurements and protein
sequences, harbor complex hidden structure that reflects its underlying
biological mechanisms. For example, high-throughput abundance measurements
provide a snapshot the global state of a living cell, while homologous
protein sequences encode the residue-level logic of the proteins' function
and provide a snapshot of the evolutionary trajectory of the protein family.
In this work I describe algorithmic approaches and analysis software I
developed for uncovering hidden structure in both kinds of data.
Clustering is an unsurpervised machine learning technique commonly used
to map the structure of data collected in high-throughput experiments,
such …
Mechanisms And Regulation Of Resection In Dna Damage Response, Sharad C. Paudyal
Mechanisms And Regulation Of Resection In Dna Damage Response, Sharad C. Paudyal
Arts & Sciences Electronic Theses and Dissertations
Deoxyribonucleic acid (DNA) encodes genetic information essential for cell survival and function. However, it is constantly under assault from endogenous and exogenous damaging agents that not only threaten our own survival but also affect the faithful transmission of genetic information to our offspring. Double-strand breaks (DSBs) are one of the most hazardous forms of DNA damage, which if unrepaired or improperly repaired could lead to plethora of systemic human diseases including cancer. To deal with this problem, cells have evolved with a mechanism called DNA damage response (DDR) to detect, signal, and repair the breaks by inducing multiple cellular events. …
Exploring Host-Virus Interactions In Caenorhabditis Nematodes, Kevin Chen
Exploring Host-Virus Interactions In Caenorhabditis Nematodes, Kevin Chen
Arts & Sciences Electronic Theses and Dissertations
Caenorhabditis elegans is a powerful model organism that has elucidated many biological questions in the fields of genetics, development, and neurobiology. In addition, C. elegans has been used in the past decade to investigate host-pathogen interactions with bacteria and fungi. The recent identification of nematode viruses that naturally infect C. elegans and Caenorhabditis briggsae provides a unique opportunity to define host-virus interactions in these model hosts.
This dissertation first explored the transcriptional response of C. elegans and C. briggsae to virus infection by RNA-seq. I identified a total of 320 differentially expressed genes (DEGs) in C. elegans following Orsay virus …
Specificity Determination By Paralogous Winged Helix-Turn-Helix Transcription Factors, Adam Joyce
Specificity Determination By Paralogous Winged Helix-Turn-Helix Transcription Factors, Adam Joyce
Arts & Sciences Electronic Theses and Dissertations
Transcription factors (TFs) localize to regulatory regions throughout the genome, where they exert physical or enzymatic control over the transcriptional machinery and regulate expression of target genes. Despite the substantial diversity of TFs found across all kingdoms of life, most belong to a relatively small number of structural families characterized by homologous DNA-binding domains (DBDs). In homologous DBDs, highly-conserved DNA-contacting residues define a characteristic ‘recognition potential’, or the limited sequence space containing high-affinity binding sites. Specificity-determining residues (SDRs) alter DNA binding preferences to further delineate this sequence space between homologous TFs, enabling functional divergence through the recognition of distinct genomic …
Nuclear Export Factor 3 Regulates The Localization Of Small Nucleolar Rnas, Melissa Wanling Li
Nuclear Export Factor 3 Regulates The Localization Of Small Nucleolar Rnas, Melissa Wanling Li
Arts & Sciences Electronic Theses and Dissertations
Metabolic diseases, such as obesity and diabetes, are associated with excess levels of lipids, which can lead to organelle dysfunction, cell death and eventually organ dysfunction. This process, termed lipotoxicity, is still not completely understood. In a genetic screen used to identify genes critical for lipotoxicity, the Schaffer lab has identified small nucleolar RNAs (snoRNAs) within the ribosomal protein L13a (Rpl13a) locus that mediate the cellular response to lipotoxic and general metabolic stress. These snoRNAs are non-canonical in that they accumulate in the cytosol after metabolic stresses like lipotoxicity and oxidative stress, suggesting that cells have specific mechanisms for regulating …
Designing Epigenome Editing Tools To Understand The Functional Role Of Dna Methylation Changes In Cancer, James Mcdonald
Designing Epigenome Editing Tools To Understand The Functional Role Of Dna Methylation Changes In Cancer, James Mcdonald
Arts & Sciences Electronic Theses and Dissertations
DNA methylation is known to silence gene expression in the context of imprinting, X-chromosome inactivation, and retrotransposon silencing. However, the role of DNA methylation in silencing gene expression outside of these contexts is not fully understood. This is especially true in diseases such as cancer, where normal DNA methylation patterns are significantly altered. In breast cancer as well as nearly all cancer types, most of the genome loses DNA methylation while small regions of the genome gain methylation. DNA methylation generally correlates with decreased gene expression when present at a gene promoter. Therefore, these regions of hypo- and hyper-methylation may …
The Role Of Rna Interference In The Control Of Leishmania Rna Virus 1 Infection, Erin Acino Brettmann
The Role Of Rna Interference In The Control Of Leishmania Rna Virus 1 Infection, Erin Acino Brettmann
Arts & Sciences Electronic Theses and Dissertations
The presence of Leishmania RNA virus 1 (LRV1) in parasites of the Leishmania (Viannia) subgenus increases the virulence of the parasite in mouse models of leishmaniasis and is correlated with treatment failure, relapse, and the development of mucocutaneous disease in humans. LRV1 is not shed or infectious; rather, the infection is persistent, and as yet it is unknown how the parasite controls virus levels. Many eukaryotic organisms use RNA interference (RNAi) to limit virus replication, and Leishmania (Viannia) parasites have an active RNAi pathway. To determine whether Leishmania are capable of using RNAi to control LRV1, we sequenced sRNAs from …
The Rpl13a Snorna U33 Forms Novel Snornps During Lipotoxicity, Miquia Sherree Henderson
The Rpl13a Snorna U33 Forms Novel Snornps During Lipotoxicity, Miquia Sherree Henderson
Arts & Sciences Electronic Theses and Dissertations
Lipid overload contributes to the pathogenesis of diabetic complications, causing tissue damage and cell death in a number of organ systems. This process is termed lipotoxicity. Animal and cell culture studies have demonstrated that oxidative stress and endoplasmic reticulum stress are major pathways engaged in the lipotoxic response. However, the molecular mechanisms of lipotoxicity are not well understood. A genetic screen revealed that small nucleolar RNAs (snoRNAs) encoded in the introns of the Rpl13a locus are critical for cell death in response to lipotoxicity. Initial studies have suggested that the Rpl13a snoRNAs function in this pathway through non-canonical modes of …
Mechanisms Of G Protein Regulation By Rgs Proteins And Small Molecule Inhibitors, Stanley Michinobu Kanai
Mechanisms Of G Protein Regulation By Rgs Proteins And Small Molecule Inhibitors, Stanley Michinobu Kanai
Arts & Sciences Electronic Theses and Dissertations
G protein coupled receptors transduce diverse extracellular signals like hormones, neurotransmitters, and photons to specific cellular responses through heterotrimeric G proteins. G proteins activate numerous effectors and signal transduction pathways, and therefore the regulation of G proteins is crucial for faithful propagation of specific cellular and physiological responses. A better understanding of the mechanisms that regulate G proteins should provide new insight into signaling pathways that govern healthy and disease states, and also provide opportunities for discovery of novel therapeutic targets.Regulator of G protein signaling (RGS) proteins are crucial regulators of G proteins, for they control amplitude and duration of …
Structural, Biophysical, And Functional Studies Of Trem2 In Neurodegenerative Disease, Daniel L. Kober
Structural, Biophysical, And Functional Studies Of Trem2 In Neurodegenerative Disease, Daniel L. Kober
Arts & Sciences Electronic Theses and Dissertations
Alzheimer's disease (AD) and other neurodegenerative diseases present a large and growing challenge to global health. The immune system, particularly the innate immune system, is increasingly recognized as having a major role in these pathologies. The innate immune system is responsible to contain disease and promote healing. However, immune misregulation exacerbates disease. The innate immunomodulatory receptor Triggering receptor expressed on myeloid cells-2 (TREM2) is expressed on myeloid cells such as dendritic cells, macrophages, and in the brain, on microglia. TREM2 is a single-pass transmembrane receptor with an extracellular Ig domain that mediates ligand binding. This protein regulates inflammation in vitro …