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Mapping Gene Function on Regulatory Networks of the Unfolded Protein Response

CSEF · 2023 Biochemistry/ Molecular Biology Honorable_mention Award

Khattar Zinia · 10

Overview

Our bodies are continuously faced with a variety of genetic and developmental stress and use stress-responsive signaling pathways to safeguard cells from these insults. These pathways thereafter activate signaling cascades to promote protective remodeling of the proteome, providing a nonstop response to external conditions to lessen impairment of the stress. The insults, however, can result in the pathogenesis of diseases. By defining the tissue-specific changes due to disease, regions of endogenous pathways that can be therapeutically targeted to improve the ramifications of disorders can be determined. To assess stress response activation in cells, stress response signaling gene sets in different tissues can be categorized. In this study, bioinformatics methods were used to correlate canonical genes from the Unfolded Protein Response consisting of ATF6, IRE1, and PERK stress pathways, and the Heat Shock Response with each other. These pathways correlated significantly across tissues, indicating that tissue-specific gene sets can be used to assess pathway activation. Analyzing correlations amongst genes in different stress pathways can establish principal pathways that cellular physiology depends on, by identifying biomarkers, and delineating the necessity to activate certain pathways in spite of certain diseases. Based on k-means clustering and pairwise correlations, target genes like HSPA5, HERPUD1, DNAJB11, MANF, PDIA6, and CALR from the UPR were found. With knowledge of such definitive biomarkers, gene functions were mapped onto regulatory networks using Gene Ontology methods. In this project, based on defined gene activity post-perturbation, target genes were entered into GO methods to output gene function. The ATF6 pathway regulates N-linked glycosylation and cell metabolism, PERK is involved in translation, ribosomal and mitochondrial processes, and XBP1s/IRE1 genes facilitate protein transport and localization. Based on such perturbation impact results, novel therapeutic methods can be developed to modulate stress proteostasis pathways without reliance on cell stress.

Source coverage

This record comes from a published award list, not a complete project archive. Its abstract comes from CSEF's public project showcase as archived by the Internet Archive before judging (https://web.archive.org/web/20230401224130/https://ca-csef.zfairs.com/showcase/ShowcaseInfo?f=838e60b7-ea75-46e8-865c-fde4864244b3); the version presented may differ.

Awards (1)

  • Category Award: HM

Competition history

  • CSEF 2023 Biochemistry/ Molecular Biology · Entry S0521

Resources

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