Biology subjects

Dinneen, E.

Publications and source records attributed to Dinneen, E..

3 recordsLinked to original sources

bioRxiv2026

The KAT2 Acetyltransferase PCAF-1 Couples Stress-Responsive Transcription to Proteostasis and Longevity

Aging erodes the capacity of cells to sense stress and maintain a functional proteome. Lysine acetyltransferases can link stress signals to gene expression, but whether boosting the activity of a single acetyltransferase can enhance stress responses to protect the aging proteome and extend healthspan remains unknown. Here we show that increasing the dosage of PCAF-1, the sole KAT2 family acetyltransferase in Caenorhabditis elegans, is sufficient to extend lifespan, preserve healthspan, and reprogram stress-responsive transcription. This program is conserved; mammalian orthologs of PCAF-1-induced genes are enriched among transcripts that decline upon KAT2A and KAT2B depletion. PCAF-1 strengthens inducible stress responses, attenuates the age-dependent decline in proteasomal degradation, and limits protein aggregation in C. elegans models of human neurodegenerative diseases, while preserving motility and survival. Mechanistically, PCAF-1 drives DAF-16/FOXO activation, and DAF-16 is required for both PCAF-1-dependent longevity and for protection against polyglutamine aggregation. These findings reveal a previously unrecognized mechanism by which KAT2 acetyltransferases promote longevity, positioning KAT2s as potential tunable regulators of proteostasis and healthspan during aging.

molecular biology↗

bioRxiv2026

Germ Granule Remodeling Reveals Germline Age in Caenorhabditis elegans

Germline aging limits reproductive lifespan, yet quantitative measures of germline age at cellular resolution within intact tissue remain limited. Here, we show that two germline condensates, P granules and Mutator foci, undergo systematic age-associated remodeling in Caenorhabditis elegans, changing in morphology, spatial organization, and mutual associations. From these single-nucleus features, we develop Germ Granule Clock (GG-Clock), an image-based aging clock that accurately predicts chronological age. Intermittent fasting, a pro-longevity intervention, shifts GG-Clock predictions toward a younger germline state, demonstrating the clock's responsiveness to anti-aging interventions. To make the approach broadly usable, we introduce GGProfiler, an open-source tool that automates granule segmentation and feature extraction. Together, our findings establish germ granule architecture as an interpretable, image-based readout of germline aging and provide a platform for quantifying condensate remodeling across genetic and environmental interventions, with potential translation to other systems.

cell biology↗

bioRxiv2024

Universal Single Copy Knock-In System in Caenorhabditis elegans: One Plasmid to Target All Chromosomes

Successful transgenesis in model organisms has dramatically helped us understand gene function, regulation, genetic networks, and potential applications. Here, we introduce the universal single-copy knock-in system (Universal SKI System or U-SKI), designed for inserting any transgene by CRISPR/Cas9 in the Caenorhabditis elegans genome. The Universal SKI System takes advantage of a plasmid (pSKI), which can also be used for extrachromosomal arrays, to facilitate the insertion of a transgene at specific safe harbor loci on each autosomal chromosome. The pSKI plasmid contains multiple restriction sites for easy cloning and serves as a CRISPR/Cas9-based insertion repair template because it has two synthetic and long homology arms that recombine with the SKI cassettes. This system also uses a single crRNA guide, which acts as a Co-CRISPR enrichment marker. Overall, the Universal SKI System is highly flexible; with the same Universal SKI cassette on each autosome, researchers can select the insertion site and streamline tracking while reducing the complexity of expressing single-copy transgenes in C. elegans.

genetics↗