Biology subjects

Briggs, C.

Publications and source records attributed to Briggs, C..

3 recordsLinked to original sources

bioRxiv2026

RNA degradation by ribonuclease T2 is required for phosphate homeostasis in S. cerevisiae

Inorganic phosphate (Pi) is a critical building block for key biomolecules including ATP, DNA, RNA, and phospholipids. Consequently, cells monitor phosphate levels and acquire phosphate when intracellular levels become low. Here we demonstrate an unanticipated connection between the enzymatic activity of the S. cerevisiae RNase T2 ortholog, Rny1, and inorganic phosphate availability. Rny1 has been studied for its role in autophagy-linked RNA degradation under starvation conditions. Here we find that in nutrient-rich conditions, cells lacking Rny1 function exhibit phosphate starvation phenotypes and aberrantly activate the PHO signaling pathway despite the presence of high levels of inorganic phosphate in the growth media. This activation is evidenced by increased PHO gene transcript levels and increased nuclear localization of Pho4 in rny1{Delta} strains. Complementation of rny1{Delta} with wild-type RNY1 and human RNase T2 restores PHO transcript levels to those typically observed in exponentially growing cells. This implicates RNase T2-dependent RNA degradation as required for maintaining intracellular phosphate levels, even under phosphate-replete conditions. Furthermore, consistent with its potential role in freeing phosphate from degraded RNA, RNY1 expression is itself further induced under phosphate-limited conditions. These observations suggest that RNase T2-mediated RNA decay is a part of a potentially conserved metabolic recycling pathway that provides Pi to growing cells. These findings reframe RNA as a key metabolic resource and positions RNase T2 enzymes, and their function in RNA degradation, as an unexpected player in phosphate homeostasis. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=151 SRC="FIGDIR/small/739639v1_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@119a9borg.highwire.dtl.DTLVardef@1bd5b13org.highwire.dtl.DTLVardef@a67bdcorg.highwire.dtl.DTLVardef@dcfd4_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2026

A combinatorial genetics approach reveals limits to redundancy within Plasmodium falciparum invasion ligand families

To maintain infection in the human bloodstream, Plasmodium falciparum parasites undergo repeated cycles of invasion of and multiplication inside red blood cells (RBCs). Two protein families, the Erythrocyte binding-like (EBA) and Reticulocyte binding-like (Rh) proteins, are known to play a key role in invasion, mediating early stages of attachment of the P. falciparum merozoite to the host RBC. There is a degree of redundancy within these families, such that disrupting the function of individual EBA/Rh proteins in vitro is not sufficient to prevent invasion. By employing a novel approach to disrupt multiple EBA and Rh genes in combination, we systematically assessed functional interdependency across these families for the first time. This analysis, and further characterisation of mutant parasites, revealed that disruption of some pairs of EBA/Rh ligands significantly impacted P. falciparum invasion, whereas others did not. Disruption of PfEBA175 in combination with either PfRh2b or PfRh4 significantly reduced parasite multiplication in vitro, indicating that the remaining EBA/Rh proteins could not fully compensate for the absence of these three key invasion ligands. PfEBA175, PfRh2b and PfRh4 may therefore represent a critical nexus of the parasite invasion machinery, and combinatorial approaches that target these specific ligands could be a beneficial therapeutic approach.

microbiology↗

bioRxiv2018

Resistant potato starch fuels beneficial host-microbe interactions in the gut

Interactions between diet, the microbiota, and the host set the ecological conditions in the gut and have broad implications for health. Prebiotics are dietary compounds that may shift these conditions towards health by promoting the growth of beneficial microbes. Pigs fed a diet amended with 5% resistant potato starch (RPS) exhibited alterations associated with gut health relative to swine fed an unamended diet (CON). RPS intake increased abundances of anaerobic Clostridia in feces and several tissues, as well as intestinal concentrations of butyrate. Functional gene amplicons suggested bacteria similar to Anaerostipes hadrus were stimulated by RPS intake. The CON treatment exhibited increased abundances of several genera of Proteobacteria (which utilize respiratory metabolisms) in several location. RPS intake increased the abundance of regulatory T cells in the cecum, but not periphery, and cecal immune status alterations were indicative of enhanced mucosal defenses. A network analysis of host and microbial changes in the cecum revealed that regulatory T cells positively correlated with butyrate concentration, luminal IgA concentration, expression of IL-6 and DEF1B, and several mucosa-associated bacterial taxa. Thus, the administration of RPS modulated the microbiota and host response, improved cecal barrier function, promoted immunological tolerance, and reduced the niche for bacterial respiration.\n\nImportanceThe gut microbiota is central to host health. Many disease states and disorders appear to arise from interactions between the gut microbial community and host immune system. As a result, methods and interventions to support the growth and activity of beneficial gut microbes are being actively pursued. Feeding the gut microbiota with dietary compounds, known as prebiotics, is one of the most promising ways to support gut health. Here we describe a successful prebiotic intervention in weaning swine, a relevant translational model for human health. This work unites microbial and immunological data and demonstrates one way a prebiotic intervention can play out for the benefit of the host.

systems biology↗