Biology subjects

Murphy, H.

Publications and source records attributed to Murphy, H..

5 recordsLinked to original sources

bioRxiv2026

Multicellularity and virulence in the budding yeast, Saccharomyces cerevisiae

In the real world, microbes must cope with environmental fluctuations, compete for scarce resources, and avoid predation. One adaptation to survive this tangled web is the formation of multicellular aggregates, such as biofilms, which are known to be associated with pathogenicity. Despite the importance of the yeast Saccharomyces cerevisiae to biomedical research, little is known about the natural variation in its multicellular, biofilm-related traits. We investigated five multicellular phenotypes in a diverse, worldwide panel of ~1000 isolates. We found that all traits varied significantly and ~2/3 of the isolates expressed at least one multicellular trait. Both recent ecology and evolutionary history explained some of this variation, with clinical isolates exhibiting increased levels of three biofilm-related traits. When tested against wax moth larvae, hyper-multicellular isolates tended to be more virulent than non-multicellular isolates. Genome-wide association analysis on each trait suggested a genetic architecture of many small effect loci, compatible with polygenic adaptation. Only four genes, SLN1, ECM5, MLP2, and ECM9, were shared among the traits; deletion of MLP2 and ECM9 verified their association with multicellularity. Our results show that this yeast expresses far more multicellularity than previously appreciated and suggest that the aggregative phenotypes are likely evolving independently.

evolutionary biology↗

bioRxiv2026

Pichinde virus models intrauterine infection by hemorrhagic fever-causing arenaviruses

Arenavirus infection during pregnancy can cause severe maternal disease, congenital infection, and fetal demise. Many arenaviruses are endemic in economically disadvantaged areas and must be studied in high containment laboratories, which has limited our understanding of arenavirus pathogenesis in the placenta. Pichinde virus (PICV) is a nonpathogenic arenavirus that recapitulates many aspects of viral hemorrhagic fever in guinea pigs. Using a combination of experiments in human placental cells and guinea pigs, we characterized the tropism and impact of PICV infection during pregnancy. PICV replicated in human trophoblast stem cells (TSCs), TSC-derived trophoblasts, and explanted term placenta. When guinea pigs were infected at mid-gestation, PICV caused fetal demise. High infectious titers were recovered from placenta and decidua, but PICV was infrequently detected in fetal tissues or amniotic fluid. In situ hybridization confirmed that the placenta, decidua, and fetal membranes were all infected by the virus. Transcriptional profiling of PICV-infected human trophoblasts and guinea pig tissues revealed that infection upregulated canonical antiviral responses, which could contribute to placental dysfunction and pregnancy loss. Thus, PICV is safe and tractable model of zoonotic arenavirus infection during pregnancy with utility for preclinical therapeutic and vaccine development.

microbiology↗

bioRxiv2023

Leveraging whole genome sequencing to promote genetic diversity and population health in zoo-housed western lowland gorillas

The sustainability of zoo populations is dependent on maintaining genetic diversity and controlling heritable disease. Here, we explore the integration of whole genome sequencing data in the management of the international zoological population of western lowland gorillas, focusing on genetic diversity and heritable diseases. By comparing kinship values derived from classical pedigree mapping and whole genome sequencing, we demonstrate that genomic data provides a more sensitive measure of relatedness. Our analysis reveals a decrease in genetic diversity due to closed breeding, emphasizing the potential for genetic intervention to mitigate negative impact on population fitness. We identify contributing factors to the decreasing genetic diversity including breeding within a closed population, unknown kinship among potential mates, and disproportionate genetic contributions from individual founders. Additionally, we highlight idiopathic myocardial fibrosis (IMF), a common cardiovascular pathology observed in zoologically housed gorillas, and identify a novel genetic variant in the TNNI3K gene that appears to be associated with this condition. These findings underscore the importance of incorporating molecular data into ex-situ population management strategies, and advocate for the adoption of advanced genomic techniques to optimize the genetic health and diversity of zoologically housed western lowland gorillas.

zoology↗

bioRxiv2019

Variation in filamentous growth and response to quorum-sensing compounds in environmental isolates of Saccharomyces cerevisiae

In fungi, filamentous growth is a major developmental transition that occurs in response to environmental cues. In diploid Saccharomyces cerevisiae, it is known as pseudohyphal growth and presumed to be a foraging mechanism. Rather than normal unicellular growth, multicellular filaments composed of elongated, attached cells spread over and into surfaces. This morphogenetic switch can be induced through quorum sensing with the aromatic alcohols phenylethanol and tryptophol. Most research investigating pseudohyphal growth has been conducted in a single lab background, {Sigma}1278b. To investigate the natural variation in this phenotype and its induction, we assayed the diverse 100-genomes collection of environmental S. cerevisiae isolates. Using computational image analysis, we quantified the production of pseudohyphae and observed a large amount of variation. Unlike ecological niche, population membership was associated with pseudohyphal growth, with the West African population having the most. Surprisingly, most strains showed little or no response to exogenous phenylethanol or tryptophol. We also investigated the amount of natural genetic variation in pseudohyphal growth using a mapping population derived from a single, highly-heterozygous clinical isolate that contained as much phenotypic variation as the environmental panel. A bulk-segregant analysis uncovered five major peaks with candidate loci that have been implicated in the {Sigma}1278b background. Our results indicate that the filamentous growth response is a generalized, highly variable phenotype in natural populations, while response to quorum sensing molecules is surprisingly rare. These findings highlight the importance of coupling studies in tractable lab strains with natural isolates in order to understand the relevance and distribution of well-studied traits.

genetics↗

bioRxiv2017

Biofilm formation and toxin production provide a fitness advantage in mixed colonies of natural yeast isolates

Microbes exist in complex communities and can engage in social interactions ranging from cooperation to warfare. Biofilms are structured, cooperative microbial communities; they are pervasive and ancient, representing the first fossilized life. Like all cooperative communities, biofilms are susceptible to invasion by selfish individuals who benefit from cooperation, but do not contribute. The ubiquity of biofilms therefore poses a challenge to evolutionary theory. One hypothesis for biofilm stability is spatial structure: patches of related cooperative cells are able to outcompete unrelated cells. These dynamics have been explored computationally and in bacterial systems; however, their relevance to eukaryotic microbes remains an open question. Here, we investigate the interactions of environmental yeast isolates with different social phenotypes. Our results show that biofilm strains spatially exclude non-biofilm strains, and that biofilm spatial structure confers a consistent and robust fitness advantage in direct competition. We also find that biofilms protect against killer toxin, a warfare phenotype. During biofilm formation, cells are susceptible to toxin from nearby competitors; however, increased spatial use by biofilms provides an escape from toxin-producers. Our results suggest that yeast biofilms represent a competitive strategy, and that principles elucidated for the evolution and stability of bacterial biofilms may apply to eukaryotes.

evolutionary biology↗