Biology subjects

Singer, L.

Publications and source records attributed to Singer, L..

6 recordsLinked to original sources

bioRxiv2026

Human regnases are evolutionarily diversified antiviral restriction factors targeting viral RNA

Regnases regulate immune gene expression by degrading cellular mRNAs. Regnase-1 also targets viral RNA, but whether this activity is shared among other human Regnases remains unknown. Here, we systematically compared the antiviral properties of all four Regnases. Expression of Regnases-1-4 inhibited RNA viruses HIV-1, HIV-2, MLV, RSV, OC43 and SARS-CoV-2, but not DNA virus HSV-1. Depletion experiments demonstrated that endogenous Regnases restrict HIV-1 replication in a cell-type-dependent manner, with Regnase-1 and Regnase-4 exerting the strongest effects in T-cells and monocytes, and Regnase-2 and Regnase-3 in primary macrophages. All Regnases displayed signatures of positive selection, consistent with their roles as antiviral restriction factors, but only Regnase-1 and -4 were induced by interferons. Mechanistically, the antiviral activity of Regnases required an intact catalytic core, a CCCH zinc finger, and, in the case of Regnase-1, -2 and -3, a dimerisation motif (P/R). Chimeric Regnase-1 and Regnase-3 constructs suggested that differences in antiviral potency primarly reflect differences in RNA recognition rather than catalytic activity. Bicistronic reporter assays suggested that Regnase-1 and -4 exhibit broad targeting, whereas Regnases-2 and -3 display greater substrate selectivity and correlate in target specificity. Collectively, our findings establish Regnases as antiviral restriction factors with distinct viral RNA targeting specificities.

immunology↗

bioRxiv2025

Targets of the human antibody response to the variant surface glycoprotein of Trypanosoma brucei

Human African Trypanosomiasis (HAT) is a severe disease endemic to Sub-Saharan Africa caused by the parasite Trypanosoma brucei. Diagnosis of the chronic form of HAT relies heavily on serological screening tests that detect specific antibodies. Trypanosoma brucei parasites rely on the antigenic variation of their variant surface glycoproteins (VSG) to evade host antibody recognition. Although VSG is the primary target of host antibodies, studies of the antibody response to VSG have been limited by low-throughput approaches that allow for the analysis of only a few VSG proteins at a time, primarily in animal models. Here, we use phage immunoprecipitation sequencing (PhIP-seq) to characterize the antibody response to VSG in HAT patient serum. Using a comprehensive T7 bacteriophage display library containing peptides representing 12,108 unique T. brucei VSGs, our analysis revealed significant differences in the anti-VSG antibody between the acute and chronic forms of HAT. Our results show that, in chronic HAT, the top lobe of the VSG is the primary interface of antibody interactions. By characterizing the targets of anti-VSG immunity, we also identified a potential bias in the CATT, the most common test used for HAT screening. Finally, we were able to identify sets of seroprevalent VSG peptides for each form of the disease that successfully distinguish between infected and uninfected individuals. Our results demonstrate the utility of characterizing host antibody responses against African trypanosomes, which can reveal unique features of parasite biology while also uncovering new diagnostic targets.

microbiology↗

bioRxiv2025

Clinical Trypanosoma cruzi isolates share a common antigen repertoire that is absent from culture adapted strains

BackgroundTrypanosoma cruzi causes Chagas disease, a poorly understood and clinically heterogeneous disease. Recent work has demonstrated that parasites adapted to laboratory conditions are genomically variable, but little is known of the extent of genomic diversity from clinically isolated specimens. MethodsIn this retrospective observational genomic study, we isolated 15 T. cruzi specimens from three clinical studies of Chagas disease, representing different clinical contexts. We sequenced the genome of each strain and used single nucleotide variant (SNV) based analyses to estimate parasite genetic lineage, genomic population structure, regions of copy number plasticity, and to identify gene conversion events. In addition, we generated and annotated whole genome assemblies of each isolate. From these assemblies, we compared the repertoires of genes encoding for highly virulent and variable proteins that have been implicated in disease pathogenesis. FindingsWe identified parasites from two genetic lineages in this collection of clinical isolates. Our analysis revealed evidence of genomic instability. Diversity-generating copy number variation was statistically enriched in regions encoding the virulence-associated multigene families, while diversity-eliminating gene conversion events were enriched in regions depleted of multigene family members. We also discovered a set of multigene family members that is present in all of the clinically isolated parasite genomes and absent from all of the lab adapted strains, regardless of parasite lineage. Multigene family repertoires were more conserved among field isolated specimens of the same genetic lineage than among culture adapted strains of the same genetic type. InterpretationThis study provides whole genome sequencing data for TcV parasites isolated from naturally infected human patients with Chagas disease for the first time. Our analysis of these genomes revealed substantial genomic instability, suggesting the parasite undergoes genomic change in response to the pressures imposed by the host environment. Moreover, we observed a set of virulence-associated genes that are present exclusively within clinical isolates and absent from lab-adapted strains, indicating a potential role for these genes in parasite survival in natural hosts. These findings highlight the limitations of genetic studies focused exclusively on lab-adapted parasite strains and provide insight into the genomic features of T. cruzi that are likely to be important for clinical infection.

microbiology↗

bioRxiv2025

Testing for changes in population trends from low-cost ecological count data

O_LIAccurate and up-to-date knowledge of population trends is essential for effective biodiversity conservation, as is assessing the impact of conservation measures designed to alter these trends. Estimating population trends is challenging, however, either due to altogether insufficient data or due to so-called noisy data that do not readily allow for standard statistical analyses. In addition, many existing methods require monitoring data over long periods of time, which is in contrast to the quick interventions needed by conservation projects, especially when endangered species are involved. C_LIO_LITo address these issues, we here present birp, a novel Bayesian tool that maximizes the power to test for population trends and changes in trends under arbitrary designs, including the canonical before-after (BA), control-intervention (CI) and before-after-control-intervention (BACI) designs often used to assess conservation impact. Our model builds on classic Poisson and negative binomial models for ecological count data and infers changes in population trends jointly from data obtained with multiple survey methods such as track counts, camera trap surveys, or distance sampling, and also from limited and noisy data not necessarily collected in standardized ecological surveys. By focusing on the change itself, our method side-steps common challenges of estimating population trends and does not need to know about absolute population densities or detection probabilities. birp is open-source and available as both a standalone command line tool as well as an R-package for fast and easy use. C_LIO_LIWe illustrate the power of our tool through extensive simulations and show that changes in trends are accurately estimated under various designs, even when data are noisy and sparse, and thereby enables biodiversity research also in regions that are remote and difficult to access. C_LIO_LIUsing birp, we further test for changes in population trends of Tasmanian devils in Australia and of apex predators and their main prey in the Central African Republic. Based on these results we give general guidelines on survey designs that maximize the power to detect trends. C_LI

ecology↗

bioRxiv2022

The spatial distribution and temporal trends of livestock damages caused by wolves in Europe

Wolf populations are recovering and expanding across Europe, causing conflicts with livestock owners. To mitigate these conflicts and reduce livestock damages, authorities spend considerable resources to compensate damages, support damage prevention measures, and manage wolf populations. However, the effectiveness of these measures remains largely unknown, especially at larger geographic scales. Here we compiled incident-based livestock damage data across 21 countries for the years 2018, 2019 and 2020, during which 39,262 wolf-caused incidents were reported from 470 administrative regions. We found substantial regional variation in all aspects of the data, including the primary target species, the density of damages, their seasonal distribution, and their temporal trend. More than half of the variation in damage densities across regions is explained by the area of extensively cultivated habitats occupied by wolves and namely natural grasslands and broad-leaved forests. Regional variation in husbandry practices and damage prevention, while difficult to quantify at a continental scale, appear important factors to further modulate these incidents. As illustrated with detailed data from Germany, for instance, the relationship between the number of wolf units and damages is diminishing over time, suggesting some adaptation of livestock owners and local authorities to their presence, for example by increasing prevention efforts. As we argue, temporal trends of damage incidents, which are robust to variation in data collection across regions, are thus informative about the local intensity of the wolf-human conflict. We estimated increasing trends for the majority of regions, reflecting the current expansion of wolves across the continent. Nonetheless, many of these increases were moderate and for more than one third of all regions, trends were negative despite growing wolf populations, thus indicating that wolf-livestock conflicts can be successfully mitigated with proper management.

ecology↗

bioRxiv2019

A sparse occupancy model to quantify species interactions in time and space

Camera traps and acoustic recording devices are essential tools to quantify the distribution, abundance and behavior of mobile species. Varying detection probabilities among device locations must be accounted for when analyzing such data, which is generally done using occupancy models. We introduce a Bayesian Time-dependent Observation Model for Camera Trap data (Tomcat), suited to estimate relative event densities in space and time. Tomcat allows to learn about the environmental requirements and daily activity patterns of species while accounting for imperfect detection. It further implements a sparse model that deals well will a large number of potentially highly correlated environmental variables. By integrating both spatial and temporal information, we extend the notation of overlap coefficient between species to time and space to study niche partitioning. We illustrate the power of Tomcat through an application to camera trap data of eight sympatrically occurring duiker Cephalophinae species in the savanna - rainforest ecotone in the Central African Republic and show that most species pairs show little overlap. Exceptions are those for which one species is very rare, likely as a result of direct competition.

ecology↗