Biology subjects

Lukacisin, M.

Publications and source records attributed to Lukacisin, M..

2 recordsLinked to original sources

bioRxiv2025

Bacterial exposure drives immune ageing

The immune system is uniquely capable of both regenerating and ageing the rest of the organism based on its own state1. Understanding the driving forces behind alterations in the immune system with age2 has thus potential to lead to interventions against ageing in general3. However, the factors driving immune ageing remain largely unknown4. Here we show that alterations in response to bacterial exposure are a key driving force of immune ageing. Studying a longitudinal cohort with their immune system characterised in high-dimension2, we devised a phenotype-driven gene co-regulation analysis through which we unravel the immune-ageing role for genes regulated by miRNAs previously reported to cause gut leakiness5. Hypothesizing increased bacterial exposure as a driver of immune ageing, we estimated the exposure of each individuals immune system to bacteria through analysing the residual bacterial DNA content in their immune cells6. We found that the total bacterial load is unrelated to the subjects chronological or immune age, but predicts the magnitude of change in immune age over the next year. Finally, we rationalise previously observed alterations in cellular composition of the immune system associated with ageing2 by finding that the immune cell subtypes most increasing in their frequency are highly enriched in expressing bacterial response genes. Our results thus earmark bacterial exposure as the candidate driver to be counteracted in anti-ageing interventions and the immune cell residual bacterial DNA content as a biomarker for the immune systems most at risk of ageing. Overall, these results offer a new paradigm for investigating gut health in the context of immune ageing7,8.

immunology↗

bioRxiv2021

Ribosomal intron-mediated switch governs yeast survival in starvation

Introns are universally present in the nuclear genomes of eukaryotes1. The budding yeast, an otherwise intron-poor species, preserves two sets of ribosomal protein (RP) genes differing primarily in their introns2-4. Despite recent findings on the role of RP introns under stress and starvation5-7, understanding the contribution of introns to ribosome regulation remains challenging. Here, combining isogrowth profiling8 with single-cell protein measurements9, we found that introns can mediate inducible phenotypic heterogeneity conferring a clear fitness advantage. Osmotic stress leads to bimodal expression of the small ribosomal subunit protein Rps22B, mediated by an intron in the 5 untranslated region of its transcript. The two resulting yeast subpopulations differ in their ability to cope with starvation. Low Rps22B protein levels resulted in prolonged survival under sustained starvation, while high Rps22B levels enabled cells to grow faster after transient starvation. Further, yeast growing at high sugar concentrations - similar to those in ripe grapes - exhibit bimodal Rps22B expression when approaching stationary phase. Differential intron-mediated regulation of RP genes thus provides a way to diversify the population when starvation looms in natural environments. Our findings reveal a new role for introns in inducing phenotypic heterogeneity in changing environments and suggest that duplicated RP genes in yeast contribute to resolving the evolutionary conflict between precise expression control and environmental responsiveness10.

systems biology↗