Biology subjects

Willis, A. R.

Publications and source records attributed to Willis, A. R..

5 recordsLinked to original sources

bioRxiv2023

Parental dietary vitamin B12 causes intergenerational growth acceleration and protects offspring from pathogenic microsporidia and bacteria

The parental environment of C. elegans can have lasting effects on progeny development and immunity. Vitamin B12 exposure in C. elegans has been shown to accelerate development and to reduce killing caused by pathogenic Pseudomonas aeruginosa. Vitamin B12 is also maternally transferred to offspring, suggesting a potential role in progeny development. However, the intergenerational effects of vitamin B12 in C. elegans remain uncharacterized. Here, we show that parental exposure to dietary vitamin B12 or vitamin B12-producing bacteria results in offspring with accelerated growth. We find that this inherited acceleration phenotype is vitamin B12 dose-dependent and persists for a single generation. Progeny from vitamin B12 treated parents display reduced levels of the acdh-1 dietary sensor in the earliest larval stages, with expression of this protein recovering into adulthood. During infection with Nematocida parisii, a natural microsporidian pathogen, the offspring of worms fed vitamin B12 diets have better reproductive fitness. However, vitamin B12 diet does not affect offspring infection levels, suggesting that accelerated development provides tolerance to microsporidian infection. Offspring from parents exposed to vitamin B12 are also protected from killing by pathogenic Pseudomonas vranovensis. Vitamin B12-induced intergenerational growth acceleration and N. parisii tolerance is dependent upon the methionine biosynthesis pathway. However, protection from P. vranovensis killing is mediated through both the methionine biosynthesis and the propionyl-CoA breakdown pathways. Our results show how parental microbial diet impacts progeny development through the transfer of vitamin B12 which results in accelerated growth and pathogen tolerance.

genetics↗

bioRxiv2022

Transcriptional profiling of zebrafish identifies host factors controlling susceptibility to Shigella flexneri

Shigella flexneri is a human adapted pathovar of Escherichia coli that can invade the intestinal epithelium, causing inflammation and bacillary dysentery. Although an important human pathogen, the host response to S. flexneri is poorly understood. Zebrafish larvae, highly innovative for genomics, transcriptomics and genetic tractability, represent a valuable animal model to study human infections in vivo. Here we use a S. flexneri-zebrafish infection model to generate mRNA expression profiles of host response to S. flexneri infection at the whole animal level. The signature of early S. flexneri infection (detected at 6 hours post-infection) is dominated by immune response-related processes. Consistent with its clearance from the host, the signature of late S. flexneri infection (detected at 24 hours post-infection) is significantly changed, where only a small set of immune-related genes remain differentially expressed, including gpr84 which encodes a putative G-protein coupled receptor. Using mutant zebrafish lines generated by ENU, CRISPR mutagenesis and the F0 CRISPR knockout method, we show that gpr84-deficient larvae are more susceptible to S. flexneri infection. Together, these results highlight the power of zebrafish to model infection by bacterial pathogens and provide a community resource to investigate host response to S. flexneri infection.

microbiology↗

bioRxiv2022

A Comprehensive Survey of C. elegans Argonaute Proteins Reveals Organism-wide Gene Regulatory Networks and Functions

Argonaute (AGO) proteins associate with small RNAs to direct their effector function on complementary transcripts. The nematode C. elegans contains an expanded family of 19 functional AGO proteins, many of which have not been fully characterized. In this work we systematically analyzed every C. elegans AGO, using CRISPR-Cas9 genome editing to introduce GFP::3xFLAG tags. We have characterized the expression patterns of each AGO throughout development, identified small RNA binding complements, and determined the effects of ago loss on small RNA populations and developmental phenotypes. Our analysis indicates stratification of subsets of AGOs into distinct regulatory modules, and integration of our data led us to uncover novel stress-induced fertility and pathogen response phenotypes due to ago loss.

molecular biology↗

bioRxiv2021

Intergenerational adaptations to stress are evolutionarily conserved, stress-specific, and have deleterious trade-offs

Despite reports of parental exposure to stress promoting physiological adaptations in progeny in diverse organisms, there remains considerable debate over the significance and evolutionary conservation of such multigenerational effects. Here, we investigate four independent models of intergenerational adaptations to stress in C. elegans - bacterial infection, eukaryotic infection, osmotic stress and nutrient stress - across multiple species. We found that all four intergenerational physiological adaptations are conserved in at least one other species, that they are stress-specific, and that they have deleterious trade-offs in mismatched environments. By profiling the effects of parental bacterial infection and osmotic stress exposure on progeny gene expression across species we established a core set of 279 highly conserved genes that exhibited intergenerational changes in expression in response to stress in all species tested and provide evidence suggesting that presumed adaptive and deleterious intergenerational effects are molecularly related at the gene expression level. By contrast, we found that these same stresses did not elicit any similarly conserved transgenerational changes in progeny gene expression three generations after stress exposure. We conclude that intergenerational responses to stress play a substantial and evolutionarily conserved role in regulating animal physiology and that the vast majority of the effects of parental stress on progeny gene expression are reversible and not maintained transgenerationally.

genetics↗

bioRxiv2020

A parental transcriptional response to microsporidia infection induces inherited immunity in offspring

Inherited immunity is an emerging field and describes how the transfer of immunity from parents to offspring can promote progeny survival in the face of infection. The mechanisms of how inherited immunity is induced are mostly unknown. The intracellular parasite Nematocida parisii is a natural microsporidian pathogen of Caenorhabditis elegans. Here, we show that N. parisii-infected worms produce primed offspring that are resistant to microsporidia infection. We find that immunity is induced in a dose dependent manner and lasts for a single generation. Intergenerational immunity prevents host cell invasion by N. parisii and also enhances survival to the bacterial pathogen Pseudomonas aeruginosa. Further, we show that inherited immunity is triggered by the host transcriptional response to infection, which can also be induced through maternal somatic depletion of negative regulators PALS-22 and the retinoblastoma protein ortholog LIN-35. We show that other biotic and abiotic stresses, such as viral infection and cadmium exposure, that induce a similar transcriptional response to microsporidia can also induce immunity in progeny. Our results demonstrate that distinct stimuli can induce inherited immunity to provide resistance against multiple classes of pathogens. These results show that activation of an innate immune response can provide protection against pathogens not only within a generation, but also in the next generation.

microbiology↗