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You searched for +publisher:"University of Colorado" +contributor:("Marvin Caruthers"). Showing records 1 – 2 of 2 total matches.

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University of Colorado

1. Adams, Daniel Jack. Catalysis of Neurotransmitter Release is a Target of Alzheimer’s Disease: Etiologic Mechanism and Novel Therapeutic Potential.

Degree: PhD, 2013, University of Colorado

Alzheimer's disease is a devastating neurodegenerative syndrome that afflicts tens of millions of patients worldwide for which no effective therapy or prevention currently exists. Although the disease mechanisms remain elusive, it is clear that the 42 amino acid β-amyloid peptide is of central importance. The present work has combined structural, biochemical and in vivo analyses to uncover a catalytic role for the major synaptic vesicle protein synaptophysin in neurotransmitter release. We have found that this catalytic activity is directly targeted and inhibited by the beta-amyloid peptide causing synaptic dysfunction early in the progression of Alzheimer's disease. The novel method developed to analyze neurotransmitter release kinetics at individual synapses constitutes a significant improvement in sensitivity, accuracy and reproducibility over currently popular methods. Finally, biophysical studies were carried out to isolate and characterize truncated synthetic byproducts of beta-amyloid which inhibit its aggregation dynamics and neurotoxicity, leading to the identification of two candidates showing great promise as therapeutic agents in the fight against Alzheimer's disease. Advisors/Committee Members: Michael H.B. Stowell, Harald Junge, Michael Klymkowsky, Marvin Caruthers, Robert McLeod.

Subjects/Keywords: Alzheimer's; Amyloid; Neurotransmitter Release; Synaptobrevin; Synaptophysin; Biophysics; Cell Biology; Molecular and Cellular Neuroscience

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Adams, D. J. (2013). Catalysis of Neurotransmitter Release is a Target of Alzheimer’s Disease: Etiologic Mechanism and Novel Therapeutic Potential. (Doctoral Dissertation). University of Colorado. Retrieved from https://scholar.colorado.edu/mcdb_gradetds/26

Chicago Manual of Style (16th Edition):

Adams, Daniel Jack. “Catalysis of Neurotransmitter Release is a Target of Alzheimer’s Disease: Etiologic Mechanism and Novel Therapeutic Potential.” 2013. Doctoral Dissertation, University of Colorado. Accessed April 08, 2020. https://scholar.colorado.edu/mcdb_gradetds/26.

MLA Handbook (7th Edition):

Adams, Daniel Jack. “Catalysis of Neurotransmitter Release is a Target of Alzheimer’s Disease: Etiologic Mechanism and Novel Therapeutic Potential.” 2013. Web. 08 Apr 2020.

Vancouver:

Adams DJ. Catalysis of Neurotransmitter Release is a Target of Alzheimer’s Disease: Etiologic Mechanism and Novel Therapeutic Potential. [Internet] [Doctoral dissertation]. University of Colorado; 2013. [cited 2020 Apr 08]. Available from: https://scholar.colorado.edu/mcdb_gradetds/26.

Council of Science Editors:

Adams DJ. Catalysis of Neurotransmitter Release is a Target of Alzheimer’s Disease: Etiologic Mechanism and Novel Therapeutic Potential. [Doctoral Dissertation]. University of Colorado; 2013. Available from: https://scholar.colorado.edu/mcdb_gradetds/26


University of Colorado

2. Busha, David. A Novel Selection Technology for the Discovery of High-Affinity Human Proteins.

Degree: PhD, 2014, University of Colorado

Proteins that bind with high-affinity to cellular targets can be useful therapeutic treatments. High-throughput affinity screening of large protein libraries is often more successful at discovering novel high-affinity proteins than rational-design approaches. Display techniques such and phage and yeast display are commonly used in this screening process. However, bacteria and yeast cells can misfold or otherwise inappropriately express mammalian and human proteins due to differences in codon usage, protein folding machinery and post-translational modifications. Therefore, a display system that is entirely based in human cells could aid in the discovery of novel, high-affinity proteins. No such system has been described to date without major limitations. This thesis describes the development of a novel protein affinity selection system. This system entails the use of the human Herpes Simplex Virus 1 (HSV-1) as a particle for protein display. In this system, genes encoding proteins to be displayed are inserted into the HSV-1 chromosome via a novel recombination system. The viruses produced display the encoded proteins on their surface fused to the C-terminus of HSV-1 glycoprotein C. Large libraries of protein-displaying viruses are then subjected to a novel, competitive-infection selection procedure. Through Darwinian selection, viruses displaying proteins with high binding affinity for cell-surface targets are enriched over viruses displaying proteins with lower binding affinity. Proof-of-principle testing has shown this system can select for a gene encoding a high-affinity protein that is outnumbered 1:105 by genes encoding lower-affinity proteins in a plasmid DNA library. Further testing of this system, using a mutant library of genes encoding the CX3CL1 chemokine, identified novel CX3CL1 mutants that may bind to the CX3CR1 receptor with higher affinity than wild-type CX3CL1. This system was also used to screen a B-cell antibody library from an HIV-infected individual. This system identified several novel antibodies that are very similar to high-affinity antibodies previously discovered from the same library. The results of this work show that this novel selection system may be a widely-applicable tool for the discovery of high-affinity human and mammalian proteins. Advisors/Committee Members: Robert Garcea, Leslie Leinwand, Larry Gold, Norman Pace, Marvin Caruthers.

Subjects/Keywords: Affinity Selection; Directed Evolution; Display; HSV-1; Mammalian proteins; Proteins; Biomedical Engineering and Bioengineering; Molecular Biology; Virology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Busha, D. (2014). A Novel Selection Technology for the Discovery of High-Affinity Human Proteins. (Doctoral Dissertation). University of Colorado. Retrieved from https://scholar.colorado.edu/mcdb_gradetds/29

Chicago Manual of Style (16th Edition):

Busha, David. “A Novel Selection Technology for the Discovery of High-Affinity Human Proteins.” 2014. Doctoral Dissertation, University of Colorado. Accessed April 08, 2020. https://scholar.colorado.edu/mcdb_gradetds/29.

MLA Handbook (7th Edition):

Busha, David. “A Novel Selection Technology for the Discovery of High-Affinity Human Proteins.” 2014. Web. 08 Apr 2020.

Vancouver:

Busha D. A Novel Selection Technology for the Discovery of High-Affinity Human Proteins. [Internet] [Doctoral dissertation]. University of Colorado; 2014. [cited 2020 Apr 08]. Available from: https://scholar.colorado.edu/mcdb_gradetds/29.

Council of Science Editors:

Busha D. A Novel Selection Technology for the Discovery of High-Affinity Human Proteins. [Doctoral Dissertation]. University of Colorado; 2014. Available from: https://scholar.colorado.edu/mcdb_gradetds/29

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