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Expressing Equilibrium

Description
The study of broad therapeutic advantages of dance is a growing field of interdisciplinary study. Yet, direct health benefits of dance from a molecular standpoint are still largely unknown. Literature review of dance performance displays in birds as well as other creatures and use of creative tools to analyze the…

The study of broad therapeutic advantages of dance is a growing field of interdisciplinary study. Yet, direct health benefits of dance from a molecular standpoint are still largely unknown. Literature review of dance performance displays in birds as well as other creatures and use of creative tools to analyze the diverse, lifelong experiences of dancers helped shed some light on the subject. Although dance experience exposes harms tied to the social constraints of how the form is experiences buried under joyful takeaways of dance, research supports overall health benefits from moderate amounts of dance maintained in perfect equilibrium.
ContributorsWilliams, Caroline (Author) / Fitzgerald, Mary (Thesis director) / Moore, Marianne (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor) / School of Music, Dance and Theatre (Contributor)
Created2022-05

P2RX7 promotes a pro-memory signature in effector CD8+ T cells dependent on Zeb2 negative regulation

Description

Memory CD8+ T cells protect against secondary viral infections. They develop and maintain exclusively in circulation (e.g. central memory - Tcm) or are excluded from re-circulation (resident memory - Trm). The extracellular ATP receptor P2RX7 promotes both Tcm and Trm generation. High (P2RX7hi) P2RX7-expressing early effector cells show survival, memory…

Memory CD8+ T cells protect against secondary viral infections. They develop and maintain exclusively in circulation (e.g. central memory - Tcm) or are excluded from re-circulation (resident memory - Trm). The extracellular ATP receptor P2RX7 promotes both Tcm and Trm generation. High (P2RX7hi) P2RX7-expressing early effector cells show survival, memory and pluripotency genes. Conversely, many terminal effector (TE) and apoptosis genes are upregulated in low (P2RX7lo) P2RX7-expressing cells. Among these genes is the zinc-finger transcriptional repressor Zeb2, which promotes TE differentiation at the expense of the memory cell pool. Given that Zeb2 was higher in P2RX7lo early effector cells, we postulated that Zeb2 ablation would allow P2RX7-deficient CD8+ T cells to skew towards memory subsets. To test this, we used RNP-based CRISPR-Cas9 to knockout Zeb2 in wild type or P2RX7-deficient P14 cells. At the memory timepoint, Zeb2 ablation led to a rescue of the ability of P2RX7-deficient cells to differentiate into the CD62L+ Tcm and CD69hiCD103hi Trm subsets, as well as increase the population of each. Our data suggest that P2RX7 imprints a pro-memory signature that is, to some extent, dependent on the negative regulation of Zeb2.
ContributorsVan Dijk, Sarah (Author) / Holechek, Susan (Thesis director) / Borges da Silvs, Henrique (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor) / School of Molecular Sciences (Contributor) / School of International Letters and Cultures (Contributor)
Created2021-12

Understanding the role of the purinergic receptor P2X3 during influenza infection in the lung

Description
Purinergic receptors play an important role in the response to infectious diseases by sensing damage-associated molecular patterns (DAMPs). The P2X family of purinergic receptors is known to recognize extracellular ATP (eATP) at different affinities. One of these receptors, P2X3, shows high affinity for eATP, but its role in modulating…

Purinergic receptors play an important role in the response to infectious diseases by sensing damage-associated molecular patterns (DAMPs). The P2X family of purinergic receptors is known to recognize extracellular ATP (eATP) at different affinities. One of these receptors, P2X3, shows high affinity for eATP, but its role in modulating responses to infectious diseases has not been studied. Using the pulmonary infection model with influenza virus PR8 strain on wild type (WT) and P2RX3-deficient (P2RX3-KO) mice, we aimed to discover the role of P2RX3 in influenza infection in the lungs. We found that there was not a significant difference in the severity of disease in WT and P2RX3-KO mice during the acute phase, but there was more fibrotic tissue visible in P2RX3-KO mice lungs on day 40 post infection (p.i.) using Masson’s trichrome staining. To further investigate these differences, we analyzed myeloid cell populations and flu-specific lymphocytes in the infected lungs. We found that there was a significant decrease in the number of antigen-specific CD4+ T cells in the lungs of P2RX3-KO mice after 7 days p.i. After performing t-SNE (t-distributed stochastic neighbor embedding) analysis on CD4+ T cells of P2RX3-KO and WT mice, we discovered that P2RX3-KO mice had a population of cells which was not present in the WT mice. This population showed high expression of most proteins such as T-bet and BCL6, which is not characteristic of the typical Th1 population induced by influenza virus. Using in vitro activation and differentiation of Th1 CD4+ T cells from WT and P2RX3-KO mice, we found that P2RX3-KO CD4+ T cells had greater expression of markers related to Tfh (T follicular helper cells), such as ICOS and CXCR5, and overall hyperactivation, demonstrating irregular Th1 differentiation. Taken together, these results suggest that P2RX3 may be linked to the maintenance of “healthy” CD4+ T cells and may be important in preventing fibrosis in influenza infection.
ContributorsWhite, Emily (Author) / Florsheim, Esther (Thesis director) / Borges da Silva, Henrique (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor) / School of Life Sciences (Contributor)
Created2024-05