Biology subjects

Scharf, A.

Publications and source records attributed to Scharf, A..

5 recordsLinked to original sources

bioRxiv2026

Diapause and Developmental Arrest as Drivers of Population Resilience Through Stress

Dauer formation and L1 arrest are stress-responsive developmental strategies that enable Caenorhabditis elegans to survive unfavorable conditions. These responses are regulated by environmental cues, including food availability and pheromone signals that communicate population density. However, how dauer entry, L1 arrest, and density-dependent signaling collectively influence long-term population dynamics remains poorly understood. In this study, populations of daf-22 and daf-16 mutants with impaired dauer formation, starvation arrest, and pheromone signaling were compared under control and starvation stress. Measurements of developmental stages were used to evaluate how genotype influenced population growth, developmental stage composition, starvation response, and recovery over time. This population-level approach links individual developmental decisions and inter-organismal communication to broader patterns of persistence and population change. The results show that daf-16 and daf-22 mutant populations differed from wild type in their recovery ability following nutrient deprivation as well as in the stage distributions within the population. These findings suggest that dauer signaling contributes broadly to population persistence by coordinating developmental arrest, reproduction, survival, and recovery. Overall, this work supports the interpretation of dauer formation as a larger population level survival program rather than a single isolated developmental outcome.

genetics↗

bioRxiv2026

Few-Shot Classification of C. elegans Developmental Stages via Explainable Hierarchical Hyperbolic Graph Embeddings

Automated, accurate, and fast developmental-stage classification of C. elegans from microscopy-based morphological images is essential for aging research, drug screening, and disease modeling. However, it remains challenging due to morphological similarities between stages and the limited annotated data. In this work, we propose HyperDev, a hyperbolic few-shot learning framework that addresses these limitations by directly encoding developmental hierarchies in the embedding space, unlike conventional Euclidean approaches that treat stages as independent classes. HyperDev uses Poincare ball geometry, combined with a biologically informed developmental prior, to naturally represent stage relationships. We introduce our self-curated C. elegans dataset spanning seven developmental stages (Egg, L1-L4, Adult, Dauer) with extreme class imbalance (6-8 samples per minority class). HyperDev achieves competitive classification accuracy (76.9-88.3%) while providing intrinsic explainability across nine 7-way few-shot evaluation settings. The learned embeddings exhibited strong biological alignment (Pearson r = 0.669, p < 0.001), while significantly outperforming ProtoNet (r = 0.187), MatchingNet (r = 0.235), and RelationNet (r = 0.464). These results establish hyperbolic geometry as a principled approach to explainable few-shot learning in biological imaging, where understanding learned representations is as critical as predictive performance. Clinical RelevanceBy enabling explainable, data-efficient developmental staging from scarce samples, HyperDev supports improved phenotype quantification for aging research, disease modeling, and drug screening.

bioinformatics↗

bioRxiv2025

Chaotic behavior influenced by an environmental parameter in simulated C. elegans populations

Population dynamics can be chaotic when driven by internal feedback loops, including density-dependent mechanisms, making them predictable only for short periods of time. Since the first discovery of chaos in simple population models, many wild and laboratory populations have been characterized as chaotic. We ask whether a population simulation through a bottom-up modeling approach such as agent-based modeling can display chaotic dynamics. Here, we use wormPOP to simulate C. elegans population dynamics with changing culling parameters and calculate the largest Lyapunov Exponents of the simulated populations. The agent-based model wormPOP is a realistic simulation based on a laboratory population system with C. elegans and its food source E. coli. Our results show that depending on the percentage of culling, populations can exhibit chaotic or periodic behavior. Build-in randomization and the buffering of stress through alternative stress-resistant larva stages in C. elegans, complicates the analysis of wormPOP populations, however, the calculated LE for the identified chaotic conditions is robust to changing parameters in our analysis and fits expectations based on the scaling of LE with body size. In conclusion, agent-based models can generate realistic population dynamics that can be chaotic dependent on the chosen parameters.

ecology↗

bioRxiv2023

The ACE-inhibitor drug captopril inhibits ACN-1 to control dauer formation and aging

The renin-angiotensin-aldosterone system (RAAS) plays a well-characterized role regulating blood pressure in mammals. Pharmacological and genetic manipulation of the RAAS has been shown to extend lifespan in C. elegans, Drosophila, and rodents, but its mechanism is not well defined. Here we investigate the angiotensin-converting enzyme (ACE) inhibitor drug captopril, which extends lifespan in worms and mice. To investigate the mechanism, we performed a forward genetic screen for captopril hypersensitive mutants. We identified a missense mutation that causes a partial loss-of-function of the daf-2 receptor tyrosine kinase gene, a powerful regulator of aging. The homologous mutation in the human insulin receptor causes Donohue syndrome, establishing these mutant worms as an invertebrate model of this disease. Captopril functions in C. elegans by inhibiting ACN-1, the worm homolog of ACE. Reducing the activity of acn-1 via captopril or RNAi promoted dauer larvae formation, suggesting acn-1 is a daf gene. Captopril-mediated lifespan extension xwas abrogated by daf-16(lf) and daf-12(lf) mutations. Our results indicate that captopril and acn-1 control aging by modulating dauer formation pathways. We speculate that this represents a conserved mechanism of lifespan control. Summary StatementCaptopril and acn-1 control aging. By demonstrating they regulate dauer formation and interact with daf genes, including a new DAF-2(A261V) mutant corresponding to a human disease variant, we clarified the mechanism.

developmental biology↗

bioRxiv2021

Pollutants corrupt resilience pathways of aging in the nematode C. elegans

Delaying aging while prolonging health and lifespan is a major goal in aging research. While many resources have been allocated to find positive interventions with promising results, negative interventions such as pollution and their accelerating effect on age-related degeneration and disease have been mostly neglected. Here, we used the short-lived model organism C. elegans to analyze whether two candidate pollutants interfere with positive interventions by corrupting general aging pathways. We took advantage of the immense data sets describing the age-related remodeling of the proteome including increased protein insolubilities to complement our analysis. We show that the emergent pollutant silica nanoparticles (NP) and the classic xenobiotic inorganic mercury reduce lifespan and cause a premature protein aggregation phenotype. Silica NPs rescaled the longevity effect of genetic interventions targeting the IGF-1/insulin-like signaling pathway. Comparative mass spectrometry revealed that increased insolubility of proteins with important functions in proteostasis is a shared phenotype of intrinsic- and pollution-induced aging supporting the hypothesis that proteostasis is a central resilience pathway controlling lifespan and aging. The presented data demonstrate that pollutants corrupt intrinsic aging pathways, which results in premature aging phenotypes. Reducing pollution is therefore an important step to increase healthy aging and prolong life expectancies on a population level in humans and animals.

developmental biology↗