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Crispr/Cas9 Whole Genome Screens Reveal Novel Regulators Of Endocytic Processes In Macrophages, Jared Wollman
Crispr/Cas9 Whole Genome Screens Reveal Novel Regulators Of Endocytic Processes In Macrophages, Jared Wollman
Electronic Theses and Dissertations
Macrophages maintain tissue homeostasis by identifying and eliminating threats within their tissue microenvironment. Pattern recognition receptors allow macrophages to recognize and internalize specific ligands while macropinocytosis allows the internalization of all extracellular solutes from their environment. Without pattern recognition receptors, pathogens may grow unchecked if they cannot be detected, and without macropinocytosis, macrophages struggle to detect and move around their environment. This thesis presents the results of CRISPR/Cas9 whole-genome screens used to identify the regulators of both endocytosis (Chapter 2) and macropinocytosis (Chapter 3). In Chapter 2, we report genes regulating dextran uptake in primary murine macrophages and reveal Mrc1-mediated …
Identification Of Macropinocytosis Regulating Proteins And Signaling From Macropinosomes, Louise Monga
Identification Of Macropinocytosis Regulating Proteins And Signaling From Macropinosomes, Louise Monga
Electronic Theses and Dissertations
Understanding macrophage cell biology is important due to macrophages key roles in human health and diseases including proper immune function, wound healing, atherosclerosis, and cancer. Despite their importance, relatively little is understood about macrophage activation, growth factor signaling, and cytoskeletal regulation. This thesis presents data from investigations into mechanisms of macrophage growth factor signaling and actin polymerization for ruffling and macropinocytosis. Alt-R CRISPR-Cas9 method and dextran uptake assay were used to knock out individual genes (SHP-1, Lyn, Syk, BTK, Vav1) and determine their role in macropinocytosis and CSF-1R signaling. Dextran uptake was disrupted in SHP-1 and Lyn targeted knockout cells, …
The Contributions Of Fc Gamma Receptors And Macropinocytosis To The Internalization, Sorting And Clearance Of Antibody Coated Nanovesicles In Macrophages, George Opoku-Kusi Jr.
The Contributions Of Fc Gamma Receptors And Macropinocytosis To The Internalization, Sorting And Clearance Of Antibody Coated Nanovesicles In Macrophages, George Opoku-Kusi Jr.
Electronic Theses and Dissertations
Macrophages are tissue-resident phagocytes that play critical roles in immune response and tissue homeostasis. They have a tremendous capacity to internalize objects of various sizes ranging from nanoscale viral particles to micron sized bacteria and tumor cells. This phenomenon, termed phagocytosis for the uptake of large particles, or endocytosis for the uptake of small particles, is integral to the immune response in multicellular organisms. Macrophages express FcγRs, which are tyrosine kinase receptors that bind IgG on an opsonized target. Binding of IgG Fc domain to the extracellular domain of an FcγR triggers signaling cascades that coordinate internalization of the opsonized …