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Articles 1 - 8 of 8
Full-Text Articles in Biophysics
A Computational Micropatterning Approach To Study Caveolae And Protein Localization In Vascular Biology, Andrew B. Grespin
A Computational Micropatterning Approach To Study Caveolae And Protein Localization In Vascular Biology, Andrew B. Grespin
Electronic Theses and Dissertations
Caveolae are specialized, flask-shaped membrane invaginations highly expressed in endothelium and dysregulated in atherosclerosis. Caveolae play a central role in buffering membrane tension, yet the principles governing their spatial organization remain elusive. Thus, we sought to generate the most comprehensive and systematic analysis of blood vessel caveolar spatial organization. However, cell culturing, the backbone of human-focused biological research, does not standardly do well to model physiologically relevant cell behaviors such as migration or polarity-based tissue formation, particularly for punctate proteins and structures like caveolae. Micropatterns are cell-adhesive shapes that biophysically confine cell(s) to a user defined geometry which stereotype organelle …
Small Gtpase Regulated Intracellular Protein Trafficking In Endothelium, Caitlin Francis
Small Gtpase Regulated Intracellular Protein Trafficking In Endothelium, Caitlin Francis
Electronic Theses and Dissertations
Intracellular protein trafficking is the movement of membrane-bound organelles to and from requisite locations within the cell. Small GTPases are a critical component to the spatiotemporal accuracy of intracellular trafficking pathways as they determine the specificity and direction of organelle transport. There exists over 150 small GTPases categorized into 5 sub-families and are employed across all cell types. Despite their universal expression and relevance to cellular function, small GTPases remain incompletely understood across tissue types. In various instances, the trafficking pathway of a particular Rab in one cell type may belong to a completely disparate pathway in another cell type. …
Foldamers Reveal And Validate Therapeutic Targets Associated With Toxic Α-Synuclein Self-Assembly, Jemil Ahmed, Tessa C. Fitch, Courtney M. Donnelly, Johnson A. Joseph, Tyler D. Ball, Mikaela M. Bassil, Ahyun Son, Chen Zhang, Aurélie Ledreux, Scott Horowitz, Yan Qin, Daniel Paredes, Sunil Kumar
Foldamers Reveal And Validate Therapeutic Targets Associated With Toxic Α-Synuclein Self-Assembly, Jemil Ahmed, Tessa C. Fitch, Courtney M. Donnelly, Johnson A. Joseph, Tyler D. Ball, Mikaela M. Bassil, Ahyun Son, Chen Zhang, Aurélie Ledreux, Scott Horowitz, Yan Qin, Daniel Paredes, Sunil Kumar
Chemistry and Biochemistry: Faculty Scholarship
Parkinson’s disease (PD) is a progressive neurodegenerative disorder for which there is no successful prevention or intervention. The pathological hallmark for PD involves the self-assembly of functional Alpha-Synuclein (αS) into non-functional amyloid structures. One of the potential therapeutic interventions against PD is the effective inhibition of αS aggregation. However, the bottleneck towards achieving this goal is the identification of αS domains/sequences that are essential for aggregation. Using a protein mimetic approach, we have identified αS sequences-based targets that are essential for aggregation and will have significant therapeutic implications. An extensive array of in vitro, ex vivo, and in vivo assays …
The Role Of Ehd2 In Endothelial Cells, Rachael Judson
The Role Of Ehd2 In Endothelial Cells, Rachael Judson
Electronic Theses and Dissertations
The role of EHD2 in terms of Cav1 interaction had not been previously characterized and was the main goal of this research. Cav1 has been shown to lead to the ubiquitination of Rac1. Because of this, the role of EHD2 in Rac1 regulation was investigated. An increase in long-term migration in endothelial cells was observed and suggested that EHD2 impacts the RhoA pathway instead of the Rac1 pathway. This lead to the hypothesis that EHD2 controls a part of the RhoA pathway. This hypothesis is supported by the loss of filamentous actin and an increase in serrated junctions in cells …
A Biophysical Investigation Of Hiv-1 Envelope Cytoplasmic-Tail Mediated Retention In The Gag Lattice, Nicholas Scott Groves
A Biophysical Investigation Of Hiv-1 Envelope Cytoplasmic-Tail Mediated Retention In The Gag Lattice, Nicholas Scott Groves
Electronic Theses and Dissertations
The infectivity of Human Immunodeficiency Virus is critically dependent on successful incorporation of the trimeric viral envelope glycoprotein, Envelope (Env), into Gag lattice assembly sites on the host-cell plasma membrane during virus biogenesis. The mechanistic nature of interaction between Gag, the structural protein, and Env, the viral spike, are dependent on the Gag matrix (MA) and Env cytoplasmic tail (CT) domains. Env laterally diffuses on the host cell plasma membrane until encountering a budding Gag lattice, where it is retained until particle scission and release. The mechanism of Env entry and retention in the lattice remains elusive and enigmatic. Here …
Optimized Microbial Recombinant Production Of Hiv-1 Anti-Envelope Antibody Fragments With Applications To Single Particle Tracking Of Virus Assembly, Merissa Michelle Bruns
Optimized Microbial Recombinant Production Of Hiv-1 Anti-Envelope Antibody Fragments With Applications To Single Particle Tracking Of Virus Assembly, Merissa Michelle Bruns
Electronic Theses and Dissertations
In my findings, I have established a set series of protocols to recombinantly produce, purify and apply various fluorescent probes in vitro for the fluorescent labeling and study of the human immunodeficiency virus type 1 (HIV-1) envelope (Env) protein during HIV viral assembly. There remains insufficient knowledge about the molecular dynamics and interactions of HIV-1 Env protein with its counterpart, Gag, on the inner host cell surface during assembly of a mature virus particle. There also remains an insufficient amount of data for the understanding and clarification of the mechanism of action of a known host cell HIV-1 restriction factor, …
Quantification Of Mitochondrial Zinc Homeostasis And Analysis Of Zinc And Polyamine-Mediated Axonal Trafficking, Dylan Hunt Fudge
Quantification Of Mitochondrial Zinc Homeostasis And Analysis Of Zinc And Polyamine-Mediated Axonal Trafficking, Dylan Hunt Fudge
Electronic Theses and Dissertations
The zinc ion is an important emerging signaling molecule for biological processes. In this work we engineered improved zinc sensors based on our previously developed fluorescent sensor GZnP1 to provide sensors with a higher fluorescent readout, faster kinetics, and a superior sensitivity to zinc. We utilized these zinc sensors and further developed the sensors to answer questions pertaining to biological zinc. We showed the labile zinc concentration in the mitochondrial matrix was less than 1 pM while the labile zinc concentration in the cytosol and mitochondrial IMS were comparable (~100 pM) across four different cell lines. Using these zinc sensors …
Cellular And Organismal Ramifications Of De Novo Purine Synthesis Dysregulation, Randall Craig Mazzarino
Cellular And Organismal Ramifications Of De Novo Purine Synthesis Dysregulation, Randall Craig Mazzarino
Electronic Theses and Dissertations
Purines are a class of nitrogenous bases and are essential small molecules to life. Purines are used within the cell as genetic information carriers, energy currency, signaling molecules, and cofactors for multiple processes. They are formed through de novo and salvage pathways found in cells across the phylogenetic tree. The substrates of enzymes within de novo purine synthesis are known to influence other processes within the cell, such as energy homeostasis. In humans, de novo purine synthesis disorders are rare, with around 100 people identified. These patients exhibit a range of phenotypes, with varying degrees of mental retardation, seizure activity, …