Life Sciences Commons^™

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 …

The Distinct Expressions Of Integrins Αdβ2 And Αmβ2 Differently Regulate Macrophage Migration In 3d Matrix In Vitro And In Tissue During Inflammation, Kui Cui

Electronic Theses and Dissertations

Chronic inflammation is an essential mechanism during the development of cardiovascular and metabolic diseases. The outcome of diseases depends on the balance between the migration and accumulation of macrophages in damaged tissues. Macrophage motility is highly regulated by adhesive receptors, integrins. Namely, intermediate expression of integrin supports macrophage migration, while a high integrin density inhibits it. Our studies are focused on evaluation of the contribution of related integrins α_Dβ₂ and α_Mβ₂ to macrophage migration and development of chronic inflammation.

We found that integrin α_Dβ₂ is upregulated on M1-macrophages in vitro and …

Identification Of Host Factors Required For Yersinia Pestis Macrophage Intracellular Survival And Their Impact On Vacuole Maturation, Acidification And Trafficking., Michael Graylin Connor

Electronic Theses and Dissertations

Y. pestis is a facultative intracellular pathogen and the causative agent of plague. This bacterium, while most noted or the Black Death during the European 14^th century, is not a historic pathogen but a re-emerging pandemic with both domestic and global impact. Y. pestis is capable of colonizing the macrophage, and actively subverts phagolysosome maturation to establish a replicative niche known as the Yersinia containing vacuole (YCV). The exploited host factors required to support the YCV are unknown. Here we identified a comprehensive list of host factors required for Y. pestis survival through a genome-wide RNAi high-throughput screen. We …