Biology subjects

Gribble, K. E.

Publications and source records attributed to Gribble, K. E..

6 recordsLinked to original sources

bioRxiv2025

Impact of inhibitors of histone post-translational modifications on lifespan, reproduction, and stress response in the rotifer Brachionus manjavacas

Epigenetic modifications, including histone post-translational modifications, are central drivers of age-associated structural and functional changes in the genome, influencing gene expression and cellular resilience. Our objective was to determine the effects of inhibiting histone deacetylases (HDACs) and the histone methyltransferase SETDB1 on lifespan, reproduction, and stress response in the rotifer Brachionus manjavacas, a model organism for aging studies. We exposed rotifers to three pharmaceutical compounds, including the HDAC inhibitors {beta}-hydroxybutyrate and sodium butyrate and the SETDB1 inhibitor mithramycin A. We quantified changes in the global histone modification levels by immunoblotting, and measured lifespan, reproduction, and heat stress resistance in the drug-treated rotifers relative to a control. Global histone acetylation levels increase with {beta}-hydroxybutyrate and sodium butyrate treatments. Histone 3 K9 trimethylation (H3K9me3) levels were reduced by treatment with mithramycin A. {beta}-hydroxybutyrate significantly extended lifespan without significantly modifying heat stress resistance. In contrast, mithramycin A increased lifespan and enhanced heat stress tolerance, demonstrating a dual protective effect. Sodium butyrate specifically improved heat stress resistance without affecting overall lifespan. Importantly, none of the three treatments had a significant impact on lifetime reproduction. These findings provide insights into the role of histone modifications in aging and suggest potential interventions targeting epigenetic marks to promote longevity and resilience.

physiology↗

bioRxiv2025

Timing the initiation of sex: Delay mechanisms alter fitness outcomes in a rotifer population model

Species that inhabit variable environments have complex mechanisms to precisely time their life-history transitions as conditions change. One such mechanism in rotifers is a block on sexual reproduction that extends across multiple asexual generations after emergence from diapause. It has been hypothesized that this delay is advantageous in competitive and stochastic environments. Here, we develop a model of cyclically parthenogenic rotifer populations with a novel formulation of a "mictic block" that prevents sexual reproduction by females that are not sufficiently distant, generationally, from a stem ancestor that was produced sexually. We find that mictic blocks are indeed adaptive but that the most successful phenotypes have shorter blocks than previously reported and that the success of different delay phenotypes is highly dependent on the duration of the growing season. For a fixed environmental regime, a stable polymorphism is possible, wherein a phenotype with a longer block performs better in years with an average-length growing season, and a phenotype with a shorter block and lower mixis ratio performs better in years with an "extreme" growing season, whether short or long. Our model provides an eco-evolutionary framework for the study of Brachionus rotifers, a model system for non-genetic maternal effects and the evolution of sex.

evolutionary biology↗

bioRxiv2023

Maternal age effects on offspring lifespan and reproduction vary within a species

Across diverse taxa, offspring from older mothers have decreased lifespan and fitness. Little is known about whether such maternal age effects vary among genotypes for a given species, however. We compared maternal age effects among four strains of rotifers in the Brachionus plicatilis species complex. For each strain, we measured lifespan, reproductive schedule, and lifetime reproductive output of offspring produced by young, middle-aged, and old mothers. We found unexpected variability among strains in the magnitude and direction of maternal age effects on offspring life history traits. In one strain, offspring of young mothers lived 20% longer than offspring of old mothers, whereas there were no significant effects of maternal age on lifespan for the other strains. Across strains, advanced maternal age had positive effects, negative effects, or no effect on lifetime reproductive output. For all but one strain, older mothers produced offspring that had higher maximum daily reproduction early in life. Maternal age effects appear to be genetically determined traits, not features of life history strategy or due to accumulation of age-related damage in the germline. Investigating intraspecific variability is critical for understanding the ubiquity of maternal age effects and their role in the evolution of life history and aging.

evolutionary biology↗

bioRxiv2022

Development of Highly Efficient CRISPR-Mediated Gene Editing in the Rotifer Brachionus manjavacas

Rotifers have been studied in the laboratory and field for over 100 years and are an emerging modern model system for investigation of the molecular mechanisms of genome evolution, development, DNA repair, aging, life history strategy, and desiccation tolerance, and have a long been used in studies of microevolution, ecological dynamics, and ecotoxicology. However, a lack of gene editing tools and transgenic strains has limited the ability to link genotype to phenotype and dissect molecular mechanisms. To facilitate genetic manipulation and the creation of reporter lines, we developed a protocol for highly efficient, transgenerational, CRISPR-mediated gene editing in the monogonont rotifer Brachionus manjavacas by microinjection of Cas9 protein and synthetic single guide RNA into the vitellaria of young amictic (asexual) females. To demonstrate the efficacy of the method, we created knockout mutants of the developmental gene vasa and the DNA mismatch repair gene mlh3. More than half of mothers survived injection and produced offspring. Genotyping these offspring and successive generations revealed that most carried at least one CRISPR-induced mutation, with many apparently mutated at both alleles or mosaic. In addition, we achieved precise CRISPR-mediated knockin of a stop codon cassette in the mlh3 locus, with half of injected mothers producing 33% or more F2 offspring with an insertion of the cassette. These results demonstrate the efficacy of the CRISPR/Cas9 system in rotifers to provide insight into the function of specific genes and further advance rotifers as a model system for biological discovery.

genomics↗

bioRxiv2019

Maternal Effect Senescence and Fitness: A Demographic Analysis of a Novel Model Organism

Maternal effect senescence--a decline in offspring fitness with maternal age--has been demonstrated in a range of taxa, including humans. Despite decades of phenotypic studies, it remains unclear how maternal effect senescence impacts population structure or evolutionary fitness. To understand the impact of maternal effect senescence on population dynamics, fitness, and selection, we used data from individual-based culture experiments on the microscopic aquatic invertebrate, Brachionus manjavacas (Rotifera), to develop a series of matrix population models in which individuals are classified jointly by age and maternal age. By comparing the results derived from models with and without maternal effects, we found that the fitness difference due to maternal effect senescence arises primarily through decreased fertility, particularly at maternal ages corresponding to the peak reproductive output. In all models, selection gradients decrease with increasing age. They also decrease with maternal age for large maternal ages, implying that maternal effect senescence can evolve through the same process as in Hamiltons theory of the evolution of demographic senescence. We find that maternal effect senescence significantly alters population structure and fitness for B. manjavacas, a species with high maternal investment and maximum reproduction in early-to mid-life. The models developed here were built with data from an emerging model organism, and are widely applicable to evaluate the fitness consequences of maternal effect senescence across species with diverse aging and fertility schedule phenotypes.

evolutionary biology↗

bioRxiv2019

Maternal age alters offspring lifespan, fitness, and lifespan extension under caloric restriction

Maternal age has a negative effect on offspring lifespan in a range of taxa and is hypothesized to influence the evolution of aging. However, the mechanisms of maternal age effects are unknown, and it remains unclear if maternal age alters offspring response to therapeutic interventions to aging. Here, we evaluate maternal age effects on offspring lifespan, reproduction, and the response to caloric restriction, and investigate maternal investment as a source of maternal age effects using the rotifer, Brachionus manjavacas, an aquatic invertebrate. We found that offspring lifespan and fecundity decline with increasing maternal age. Caloric restriction increases lifespan in all offspring, but the magnitude of lifespan extension is greater in the offspring from older mothers. The trade-off between reproduction and lifespan extension under low food conditions expected by life history theory is observed in young-mother offspring, but not in old-mother offspring. Age-related changes in maternal resource allocation to reproduction do not drive changes in offspring fitness or plasticity under caloric restriction in B. manjavacas. Our results suggest that the declines in reproduction in old-mother offspring negate the evolutionary fitness benefits of lifespan extension under caloric restriction.

evolutionary biology↗