Drew University Library : University Archives : Theses and Dissertations
    
author Robert Sutter
title Role of Chromatin Structure in Immune Sensing of DNA
abstract The innate immune system uses pattern recognition receptors (PRRs) to sense microbial-associated molecular patterns (MAMPs). When a PRR binds a MAMP, this leads to a signal cascade through the cell resulting in transcription and production of inflammatory cytokines, such as interferon. MAMPs are molecules that are typically distinct from any molecules expressed by the human body. However, some PRRs bind to DNA, which is necessary for and not distinct from human cells. These PRRs binds DNA in order to detect viral infections and then create an interferon response to fight off the viral infection. This begs the question of how the PRR can distinguish between host and non-host DNA to prevent the erroneous production of interferon. Since the host cell has a tremendous amount of DNA, the DNA must be extremely organized and structured to fit all of the DNA into the cell. The cell does this by wrapping the DNA around a circular protein called a histone and together, the DNA wrapped around the histone is called a nucleosome. Perhaps this structure also serves a dual purpose of organizing the DNA and preventing host DNA from being sensed by PRRs. We hypothesized that host cell DNA in a nucleosome will not cause an interferon response while nucleosomal DNA without the histone will cause an interferon response. Also, we hypothesized that histones will actively inhibit the DNA sensor instead of just blocking the DNA sensor from binding to the DNA. We investigated the first hypothesis by stimulating cells with either nucleosomes or nucleosomal DNA and measuring the interferon response. We tested the second hypothesis by stimulating cells with either plasmid, histone and plasmid, or histone and measured the interferon response. Our data showed that a smaller interferon response is produced by nucleosomes versus nucleosomal DNA and that histones actively inhibit DNA sensors. This provides a mechanism for how cells can distinguish between host and non-host DNA and avoid erroneous interferon signaling.
school The College of Liberal Arts, Drew University
degree B.S. (2021)
advisor Brianne Barker
committee Stephen Dunaway
Bjorg Larson
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