Biology subjects

Barker, C.

Publications and source records attributed to Barker, C..

5 recordsLinked to original sources

bioRxiv2026

SPIN1 selectively silences evolutionarily young transposable elements through chromatin regulation

Mammalian genomes encode multiple transposable element (TE) silencing pathways that distinguish their targets through different molecular features, with KRAB zinc finger proteins recognizing DNA sequence, the HUSH complex sensing intronless transcripts, and the PIWI-piRNA pathway using small RNA guides. How chromatin state itself contributes to TE recognition remains less defined. Here we identify Spindlin1 (SPIN1), a three-Tudor-domain histone reader implicated in germline piRNA-directed DNA methylation, as a transcriptional repressor of evolutionarily young TEs in mouse embryonic stem cells. SPIN1 selectively binds LINE and ERV loci carrying H3K4me3 and H3K9me3, a chromatin signature enriched at young, transcription-permissive elements, and recognition of these marks by Tudor domains 1 and 2 is required for TE targeting. SPIN1 engages SPINDOC as a Tudor 1 and 3-dependent cofactor whose loss phenocopies SPIN1 depletion, and associates with the H3K9 methyltransferases SETDB1 and G9a. SPIN1 loss reduces H3K9me3 and is accompanied by increased chromatin accessibility, without altering DNA methylation. Thus, SPIN1 uses a histone-state-based mechanism to identify and repress young TEs in pluripotent cells, mechanistically distinct from its germline mode in which SPIN1 cooperates with the PIWI-piRNA pathway to promote DNA methylation, illustrating how a single histone reader engages distinct silencing machineries across cellular contexts.

molecular biology↗

bioRxiv2025

Storage Protein-Mediated Translation Control Links Juvenile Diet to Longevity in Drosophila

Dietary restriction (DR), whether applied during adulthood or juvenile stages, extends lifespan across diverse species. However, the mechanisms by which early-life dietary interventions influence adult physiology and longevity remain poorly understood. Here, using Drosophila as a model, we demonstrate that protein restriction during the larval stage (early-life protein restriction, ePR) promotes adult lifespan by reducing storage protein levels. Stable isotope tracing reveals that dietary amino acids obtained in the larval stage are retained into adulthood, especially incorporated into ribosomal proteins. This is mediated by larval serum protein 2 (Lsp2), a major storage protein, whose expression is durably downregulated by ePR. Both dietary (ePR) and genetic (Lsp2-RNAi) reduction of the protein storage lead to decreased ribosomal protein levels and translation activity in early adulthood. Notably, these storage proteins are enriched in aromatic amino acids such as tyrosine, and larval tyrosine restriction alone is sufficient to suppress translation and promote longevity. These findings show that storage proteins mediate the effect of larval nutrition on adult longevity via controlling translation. Our study uncovers a previously unrecognised mechanism of nutritional memory that links early-life diet to life-long organismal health.

physiology↗

bioRxiv2018

Chiral DNA sequences as commutable reference standards for clinical genomics

Chirality is a geometric property describing any object that is inequivalent to a mirror image of itself. Due to its 5-3 directionality, a DNA sequence is distinct from a mirrored sequence arranged in reverse nucleotide order, and is therefore chiral. A given sequence and its opposing chiral partner sequence share many properties, such as nucleotide composition and sequence entropy. Here we demonstrate that chiral DNA sequence pairs also perform equivalently during molecular and bioinformatic techniques that underpin modern genetic analysis, including PCR amplification, hybridization, whole-genome, target-enriched and nanopore sequencing, sequence alignment and variant detection. Given these shared properties, synthetic DNA sequences that directly mirror clinically relevant and/or analytically challenging regions of the human genome are ideal reference standards for clinical genomics. We show how the addition of chiral DNA standards to patient tumor samples can prevent false-positive and false-negative mutation detection and, thereby, improve diagnosis. Accordingly, we propose that chiral DNA standards can fulfill the unmet need for commutable internal reference standards in precision medicine.

genomics↗

bioRxiv2018

What lies beneath: a spatial mosaic of Zika virus transmission in the 2015-2016 epidemic in Colombia

Time series data provide a crucial window into infectious disease dynamics, yet their utility is often limited by the spatially aggregated form in which they are presented. When working with time series data, violating the implicit assumption of homogeneous dynamics below the scale of spatial aggregation could bias inferences about underlying processes. We tested this assumption in the context of the 2015-2016 Zika epidemic in Colombia, where time series of weekly case reports were available at national, departmental, and municipal scales. First, we performed a descriptive analysis, which showed that the timing of departmental-level epidemic peaks varied by three months and that departmental-level estimates of the time-varying reproduction number, R(t), showed patterns that were distinct from a national-level estimate. Second, we applied a classification algorithm to six features of proportional cumulative incidence curves, which showed that variability in epidemic duration, the length of the epidemic tail, and consistency with a cumulative normal density curve made the greatest contributions to distinguishing groups. Third, we applied this classification algorithm to data simulated with a stochastic transmission model, which showed that group assignments were consistent with simulated differences in the basic reproduction number, R0. This result, along with associations between spatial drivers of transmission and group assignments based on observed data, suggests that the classification algorithm is capable of detecting differences in temporal patterns that are associated with differences in underlying drivers of incidence patterns. Overall, this diversity of temporal patterns at local scales underscores the value of spatially disaggregated time series data.

epidemiology↗

bioRxiv2017

Preliminary results of models to predict areas in the Americas with increased likelihood of Zika virus transmission in 2017.

Numerous Zika virus vaccines are being developed. However, identifying sites to evaluate the efficacy of a Zika virus vaccine is challenging due to the general decrease in Zika virus activity. We compare results from three different modeling approaches to estimate areas that may have increased relative risk of Zika virus transmission during 2017. The analysis focused on eight priority countries (i.e., Brazil, Colombia, Costa Rica, Dominican Republic, Ecuador, Mexico, Panama, and Peru). The models projected low incidence rates during 2017 for all locations in the priority countries but identified several subnational areas that may have increased relative risk of Zika virus transmission in 2017. Given the projected low incidence of disease, the total number of participants, number of study sites, or duration of study follow-up may need to be increased to meet the efficacy study endpoints.

epidemiology↗