Biology subjects

Hutt, K.

Publications and source records attributed to Hutt, K..

5 recordsLinked to original sources

bioRxiv2024

A pervasive large conjugative plasmid mediates multispecies biofilm formation in the intestinal microbiota increasing resilience to perturbations

Although horizontal gene transfer is pervasive in the intestinal microbiota, we understand only superficially the roles of most exchanged genes and how the mobile repertoire affects community dynamics. Similarly, little is known about the mechanisms underlying the ability of a community to recover after a perturbation. Here, we identified and functionally characterized a large conjugative plasmid that is one of the most frequently transferred elements among Bacteroidales species and is ubiquitous in diverse human populations. This plasmid encodes both an extracellular polysaccharide and fimbriae, which promote the formation of multispecies biofilms in the mammalian gut. We use a hybridization-based approach to visualize biofilms in clarified whole colon tissue with unprecedented 3D spatial resolution. These biofilms increase bacterial survival to common stressors encountered in the gut, increasing strain resiliency, and providing a rationale for the plasmids recent spread and high worldwide prevalence.

microbiology↗

bioRxiv2023

eCV: Enhanced coefficient of variation and IDR extensions for reproducibility 1 assessment of high-throughput experiments with multiple replicates.

MotivationReproducibility assessment is essential in extracting reliable scientific insights from highthroughput experiments. Inconsistency between technical replicates poses a challenge, particularly clear in next generation sequencing technologies based on immunoprecipitations, where the assessment of reproducibility in peak identification is a critical analytical step. While the Irreproducibility Discovery Rate (IDR) method has been instrumental in assessing reproducibility, its standard implementation is constrained to handling only two replicates. In the current era of steadily growing sample sizes, eased by multiplexing and reduced sequencing costs, highly performing methods that handle any number of replicates are desirable. ResultsWe introduce three novel methods for reproducibility assessment in high-throughput data that handle an arbitrary number of replicates. The first, general IDR (gIDR), extends the standard IDR by adapting its Expectation-Maximization (EM) algorithm to handle distributions of any dimensions dictated by the number of replicates. The second, meta-IDR (mIDR), employs a meta-analysis approach, calculating local IDR scores for all pairs of replicates and combining them using standard probability rules. The third method introduces an "enhanced" Coefficient of Variation (eCV), ranking features based on intensity and variability, using a parametric bootstrap approach to obtain an index analogous to local IDR. Comparative analysis with traditional IDR in simulated and experimental data reveals the heightened performance of the proposed multivariate alternatives under varying scenarios, thereby addressing the critical challenge of reproducibility assessment in contemporary high-throughput experiments. Availability and implementationThe described methods are implemented as an R package: https://github.com/eclipsebio/eCV Contactinfo@eclipsebio.com

bioinformatics↗

bioRxiv2022

Fancm regulates meiotic double-strand break repair pathway choice in mammals

Meiotic crossovers are required for accurate chromosome segregation and to produce new allelic combinations. Meiotic crossover numbers are tightly regulated within a narrow range, despite an excess of initiating DNA double-strand breaks. Here, we describe the tumour suppressor FANCM as a meiotic anti-crossover factor in mammals. Crossover analyses with single-gamete and pedigree datasets both reveal a genome-wide increase in crossover frequencies in Fancm-deficient mice. Gametogenesis is heavily perturbed in Fancm loss of function mice, which is consistent with the reproductive defects reported in humans with biallelic FANCM mutations. A portion of the gametogenesis defects can be attributed to the cGAS-STING pathway. Despite the gametogenesis phenotypes in Fancm mutants both sexes were capable of producing offspring. We propose that the anti-crossover function and role in gametogenesis of Fancm are separable and will inform diagnostic pathways for human genomic instability disorders.

genetics↗

bioRxiv2020

Moderate episodic prenatal alcohol does not impact female offspring fertility in rats

Prenatal alcohol exposure (PAE) has been associated with reproductive dysfunction in offspring. However, studies in females, particularly examining long-term infertility or impacts on ovarian reserve, are lacking. The current study utilised a moderate, episodic exposure model in rats to mimic special occasion drinking, which is reported to be common during pregnancy. Our objective was to examine the consequences of this prenatal alcohol exposure on reproductive parameters in female offspring. Pregnant Sprague Dawley rats were treated with either an ethanol gavage (1g EtOH/kg body weight), or an equivalent volume of saline, on embryonic days 13.5 and 14.5 of pregnancy, resulting in a peak blood alcohol concentration of [~]0.04%. Neonatal female offspring were examined for molecular markers regulating early follicle numbers in the ovary and unbiased stereology used to quantify primordial and early growing follicle numbers. Puberty onset (age at vaginal opening and first estrous) was measured post-weaning and estrous cycles, reproductive hormones (progesterone and estradiol) and pregnancy success measured in adults (5-6 months of age). We found no evidence that any of these reproductive parameters were significantly altered by PAE in this model. This animal study provides some reassurance for women who may have consumed a small amount of alcohol during their pregnancy. However, previously published effects on offspring metabolism using this model reinforce avoidance of alcohol during pregnancy.

developmental biology↗

bioRxiv2020

Smchd1 is a maternal effect gene required for autosomal imprinting

Genomic imprinting establishes parental allele-biased expression of a suite of mammalian genes based on parent-of-origin specific epigenetic marks. These marks are under the control of maternal effect proteins supplied in the oocyte. Here we report the epigenetic repressor Smchd1 as a novel maternal effect gene that regulates imprinted expression of 16 genes. Most Smchd1-sensitive genes only show loss of imprinting post-implantation, indicating maternal Smchd1s long-lived epigenetic effect. Sm-chd1-sensitive genes include both those controlled by germline polycomb marks and germline DNA methylation imprints; however, Smchd1 differs to other maternal effect genes that regulate the latter group, as Smchd1 does not affect germline DNA methylation imprints. Instead, Smchd1-sensitive genes are united by their reliance on polycomb-mediated histone methylation marks as germline or secondary imprints. We propose that Smchd1 translates these imprints to establish a heritable chromatin state required for imprinted expression later in development, revealing a new mechanism for maternal effect genes.

genomics↗