Date of Award

8-20-2024

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Cell Biology, Neurobiology and Anatomy

First Advisor

Ed Campbell

Abstract

Inflammation is an important defense mechanism through which cells respond to pathogenic insults and damage/stress signals. Immune cells mediate extracellular inflammatory responses by synthesizing and releasing small proteins called cytokines, which play critical roles in modulating these responses. Specifically, key pro-inflammatory cytokines such as IL-1beta are released upon the assembly and activation of a multi-protein intracellular complex called the inflammasome, the most well-studied of which is the NLRP3 inflammasome. Several proteins have been identified as important regulators of cellular stress responses, including vacuole membrane protein 1 (VMP1). The present research shows that VMP1-depleted cells exhibit exacerbated cellular inflammation and are prone to mitochondrial damage using a CRISPR/Cas9 VMP1-knockout THP-1 model. Similarly, a component of the complement system, the C5a receptor, has been shown to mediate cellular stress responses by interacting on the mitochondrial surface. Present research explores the effects of a CRISPR/Cas9 C5a-knockout system on cellular inflammation in THP-1 cells.

Included in

Cell Biology Commons

Share

COinS