Cell and Developmental Biology Commons^™

Binding Affinity And Specificity Of Sh2 Domain Interactions In Receptor Tyrosine Kinase Signaling Networks, Tom Ronan

McKelvey School of Engineering Theses & Dissertations

Receptor tyrosine kinase (RTK) signaling mechanisms play a central role in intracellular signaling and control development of multicellular organisms, cell growth, cell migration, and programmed cell death. Dysregulation of these signaling mechanisms results in defects of development and diseases such as cancer. Control of this network relies on the specificity and selectivity of Src Homology 2 (SH2) domain interactions with phosphorylated target peptides. In this work, we review and identify the limitations of current quantitative understanding of SH2 domain interactions, and identify severe limitations in accuracy and availability of SH2 domain interaction data. We propose a framework to address some …

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 …

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 …

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 …

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 …

The Localization And Function Of Novel Tetrahymena Thermophila Cytoskeletal Genes Bbc29 And Bbc39, Emily K. Moore, Nicole C. Zanolli

Undergraduate Research Symposium Posters

Ciliary function is known to play an important role in many human conditions, including chronic sinus and pulmonary diseases and problems with infertility. Cilia are cytoskeletal structures that protrude from the cell body to facilitate movement. Ciliary structure is conserved throughout eukaryotes, from unicellular to multicellular organisms, including humans. A clear understanding the proteins that compose cilia and how they interact with one another will increase our knowledge about important cytoskeletal elements. Because cilia are difficult to study in multicellular organisms, the unicellular eukaryote Tetrahymena thermophila serves as a useful model for the study of cytoskeletal genes, due to their …