Biology subjects

Campos, S. E.

Publications and source records attributed to Campos, S. E..

7 recordsLinked to original sources

bioRxiv2025

Sustained ERK signaling couples the injury response to organizer formation during Hydra head regeneration

Regenerative abilities vary widely across animals, even among closely related species, and a central challenge is to compare their gene regulatory networks (GRNs) to determine which components and regulatory connections are conserved or divergent. Hydra provides a powerful system for this work: as a cnidarian, which is the sister group to bilaterians, it offers access to deeply conserved regenerative mechanisms, and species within the genus differ in regenerative phenotypes. Here, we investigate the function of extracellular signal-regulated kinase (ERK) signaling in driving head regeneration in Hydra. ERK is a conserved injury-responsive pathway implicated in regeneration across animals, including in the activation of Wnt signaling, which is necessary and sufficient to establish the Hydra head organizer, a Wnt signaling center that patterns the main body axis. We found that in Hydra vulgaris, ERK activity extends from the generic injury phase into the period when the Wnt-based head organizer forms. However, unlike in some other regenerating species, transient ERK inhibition delayed but did not block regeneration, consistent with Hydras ability to regenerate without a proliferation-dependent blastema. ERK inhibition in H. vulgaris disrupted the transcriptional activation of multiple Wnt pathway components and restricted their expression domains, providing a likely explanation for the delayed onset of head organizer formation. Comparative experiments in Hydra oligactis, which regenerates its head approximately 24 hours more slowly than H. vulgaris, revealed reduced persistence of ERK signaling and lower sensitivity to ERK inhibition. These features suggest that while injury-induced ERK activity is conserved, the mechanisms that establish the Wnt signaling center during regeneration diverge between the two species. Together, our findings identify sustained ERK activity as a critical regulator of Wnt pathway activation during Hydra head regeneration and indicate that evolutionary shifts in the ERK-Wnt regulatory architecture contribute to species-specific differences in regenerative phenotypes.

developmental biology↗

bioRxiv2025

Exposing the core genetic drivers of chronological aging in yeast cells

The chronological lifespan of Saccharomyces cerevisiae has been pivotal in advancing our understanding of aging in eukaryotic cells. However, gaining a genome-wide perspective of this trait remains challenging due to substantial discrepancies observed across large-scale gene-deletion screens. In this study, we performed a meta-analysis to compile a ranked catalog of key processes and regulators driving chronological longevity in yeast, ensuring their robustness across diverse experimental setups. These consistent chronological aging factors were enriched in genes associated with yeast replicative lifespan and orthologs implicated in aging across other model organisms. Functional analysis revealed that the downstream cellular mechanisms underlying chronological longevity in yeast align with well-established, universal hallmarks of aging, underscoring the potential of the yeast chronological aging model to investigate conserved aging processes. Additionally, we identified transcriptional regulators associated with these consistent genetic factors, uncovering potential global and local modulators of chronological aging. Among these, Tec1, a key regulator of the filamentous growth pathway, emerged as a central hub connected to multiple aging pathways. To further elucidate the functional role of this regulator, we conducted a high-resolution lifespan-epistasis screen, demonstrating that TEC1 and mitochondrial machinery promote chronological longevity in parallel, compensating for each others impaired functions. Our findings provide an integrated view of the core genetic and functional landscape underlying aging in yeast cells.

genetics↗

bioRxiv2025

Wnt signaling restores evolutionary loss of regenerative potential in Hydra

The regenerative potential of animals varies widely, even among closely-related species. In a comparative study of regeneration across the Hydra genus, we found that while most species exhibit robust whole-body regeneration, Hydra oligactis and other members of the Oligactis clade consistently fail to regenerate their feet. To investigate the mechanisms underlying this deficiency, we analyzed transcriptional responses during head and foot regeneration in H. oligactis. Our analysis revealed that the general injury response in H. oligactis lacks activation of Wnt signaling, a pathway essential for Hydra vulgaris foot regeneration. Notably, transient treatment with a Wnt agonist in H. oligactis triggered a foot-specific transcriptional program, successfully rescuing foot regeneration. Our transcriptional profiling also revealed dlx2 as a likely high-level regulator of foot regeneration, dependent on Wnt signaling activation. Our study establishes a comparative framework for understanding the molecular basis of regeneration and its evolutionary loss in closely-related species.

developmental biology↗

bioRxiv2022

Genomewide identification of subtelomeric silencing factors in budding yeast

Subtelomeric gene silencing is the negative transcriptional regulation of genes located close to telomeres. This phenomenon occurs in a variety of eukaryotes with salient physiological implications, such as cell adherence, virulence, immune-system escape, and aging. The process has been widely studied in the budding yeast Saccharomyces cerevisiae, where genes involved in this process have been identified mostly on a gene-by-gene basis. Here, we introduce a quantitative approach to study subtelomeric gene silencing, that couples the classical URA3 reporter with GFP monitoring, amenable to high-throughput flow cytometry analysis. This reporter was integrated into several subtelomeric loci in the genome, where it showed a gradual range of silencing effects. By crossing strains with this dual reporter at the COS12 and YFR057W subtelomeric query loci with gene-deletion mutants, we carried out a genome-wide, comprehensive screen for subtelomeric-silencing factors. The approach was replicable and allowed detection of expression changes caused by previously described silencing factors. We also identified new molecular players affecting this process, most of which are related to functions underlying chromatin conformation. This was the case of LGE1, a novel silencing factor herein reported, associated with histone ubiquitination. Our strategy can be readily combined with other reporters and gene perturbation collections, making it a versatile tool to study gene silencing at a genome-wide scale.

genetics↗

bioRxiv2019

A Competitive-Aging Method for Quantitative Genetic Analysis of the Chronological Lifespan of Saccharomyces cerevisiae

The chronological lifespan of budding yeast is a model of aging and age-related diseases. This paradigm has recently allowed genome-wide screening of genetic factors underlying post-mitotic viability in a simple unicellular system, which underscores its potential to provide a comprehensive view of the aging process. However, results from different large-scale studies show little overlap and typically lack quantitative resolution to derive interactions among different aging factors. We previously introduced a sensitive, parallelizable approach to measure the chronological-lifespan effects of gene deletions based on the competitive aging of fluorescence-labeled strains. Here, we present a thorough description of the method, including an improved multiple-regression model to estimate the association between death rates and fluorescent signals, which accounts for possible differences in growth rate and experimental batch effects. We illustrate the experimental procedure--from data acquisition to calculation of relative survivorship--for ten deletion strains with known lifespan phenotypes, which is achieved with high technical replicability. We apply our method to screen for gene-drug interactions in an array of yeast deletion strains, which reveals a functional link between protein glycosylation and lifespan extension by metformin. Competitive-aging screening coupled to multiple-regression modeling provides a powerful, straight-forward way to identify aging factors in yeast and their interactions with pharmacological interventions.

genetics↗

bioRxiv2018

An interaction map of transcription factors controlling gynoecium development in Arabidopsis

Flowers are composed of different organs, whose identity is defined at the molecular by the combinatorial activity of transcription factors (TFs). MADS-box TFs interact forming complexes that have been schematized in the quartet model. The gynoecium is the female reproductive part in the flower, crucial for plant reproduction, and fruit and seed production. Once carpel identity is established, a gynoecium containing many tissues arises. Several TFs have been identified as regulators of gynoecium development, and some of these TFs form complexes. However, broad knowledge about the interactions among these TFs is still scarce. In this work, we used a systems biology approach to understand the formation of a complex reproductive unit as the gynoecium by mapping binary interactions between well-characterized TFs. We analyzed over 3500 combinations and detected more than 200 protein-protein interactions (PPIs), resulting in a process specific interaction map. Topological analyses suggest hidden functions and novel roles for many TFs. Furthermore, a relationship between TFs involved in auxin and cytokinin signaling pathways and other TFs was observed. We analyzed the network by combining PPI data, expression and genetic data, allowing us to dissect it into several dynamic spatio-temporal sub-networks related to gynoecium development subprocesses.

plant biology↗

bioRxiv2017

Genome-Wide Mechanisms of Lifespan Extension by Dietary Restriction in Yeast

Dietary restriction is arguably the most promising non-pharmacological intervention to extend human life and health span. Yet, only few genetic regulators mediating the cellular response to dietary restriction are known, and the question remains which other transcription factors and regulatory pathways are involved. To gain a comprehensive view of how lifespan extension under dietary restriction is elicited, we screened the chronological lifespan of most gene deletions of Saccharomyces cerevisiae under two dietary regimens, restricted and non-restricted. We identified 472 mutants with enhanced or diminished extension of lifespan by dietary restriction. Functional analysis of such dietary-restriction genes revealed novel processes underlying longevity specifically by dietary restriction. Importantly, this set of genes allowed us to generate a prioritized catalogue of transcription factors orchestrating the dietary-restriction response, which underscored the relevance of cell-cycle arrest control as a key mechanism of chronological longevity in yeast. We show that the transcription factor Ste12 is needed for full lifespan extension and cell-cycle arrest in response to nutrient limitation; linking the pheromone/invasive growth pathway with cell survivorship. Strikingly, STE12 overexpression was sufficient to extend chronological lifespan under non-restricted conditions. Our global picture of the genetic players of longevity by dietary restriction highlights intricate regulatory cross-talks in aging cells.

genetics↗