Matthew
Tabrisky

Biochemistry REU The Set1 histone H3K4 methyltransferase alters Candida glabrata pathogenesis by controlling the expression of genes involved in cell wall formation. Life Sciences

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Matthew Tabrisky

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The WHO designated Candida glabrata as a high-priority fungal pathogen. Notably, C. glabrata ranks as the third most isolated Candida species exhibiting intrinsic resistance to azole-antifungal drugs. Therefore, there is a critical need to understand what factors contribute to the pathogenesis of C. glabrata. Our laboratory has focused on the epigenetic factor SET1 and its role in pathogenesis. Using the Galleria mellonella larvae animal infection model, we have demonstrated that Set1 is necessary for pathogenesis. Specifically, the set1? strains significantly reduce the virulence of three different background C. glabrata strains when compared to their parental strains. Because Set1 is a known epigenetic factor, we hypothesized that Set1 directly governs the expression of genes contributing to the virulence of C. glabrata. To identify Set1-dependent virulence genes, we performed RNA-sequencing, interestingly, the most differentially expressed genes identified were involved in the formation of the cell wall. To determine if Set1 directly targets these genes, chromatin immunoprecipitation will be performed using a strain that I will construct to express a 3XFLAG-tagged Set1. Currently, I have confirmed that the selection marker and 3XFLAG tag have been integrated at the SET1 locus. Next, we will remove the selection marker and perform a western blot to confirm the expression and function of the 3XFLAG-Set1 strain. We will also generate deletions of these cell wall proteins and determine if these genes alter virulence. At the conclusion, we will have determined that Set1 directly controls the expression of novel virulence genes contributing to the pathogenesis of C. glabrata. Keywords: [no keywords provided]

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Purdue University / 2024

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Matthew Tabrisky

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