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Fawcett, S.

Publications and source records attributed to Fawcett, S..

6 recordsLinked to original sources
bioRxiv2026

A tribal-scale phylogenomic perspective on ancestry and major lineages of the allotetraploid Hawaiian silversword alliance (Madieae, Compositae)

Premise of the studyDisentangling ancestry of insular plant lineages is important for resolving their evolutionary histories but often complicated by polyploidy, an overrepresented condition in remote island floras. A phylogenomic approach was used to study the origin of subgenomes of the tetraploid Hawaiian silversword alliance and advance understanding of this major example of adaptive radiation. MethodsSequences from 461 target-capture nuclear loci were phased to subgenomes of the tetraploid silversword alliance (Compositae) using assemblies from diploid North American tarweeds as clade references. Maximum-likelihood and multispecies- coalescent analyses of phased loci were conducted with and without representatives of diploid lineages throughout tribe Madieae. Key resultsAn allopolyploid origin of the silversword alliance was corroborated, with Subgenome-A phased consistently to Anisocarpus madioides and Subgenome-B phased to diploid representatives of each of three other sublineages of the "Madia" lineage. Phylogenomic analyses indicate Anisocarpus madioides is more closely related to Subgenome-A than to other tarweeds, including Anisocarpus scabridus. Subgenome trees for the silversword alliance are highly congruent with each other and with structural genomic differences between lineages. ConclusionsThese results indicate an even closer relationship of the silversword alliance to extant California tarweeds than previously understood. Anisocarpus madioides has chromosomal and ecological traits anticipated in an ancestor of the silversword alliance, with the widest geographic range among perennial tarweeds and sticky bracts completely enveloping fruits. Within the silversword alliance, robust support for four major clades reinforces the phylogenetic value of chromosomal interchanges and taxonomic insights by Asa Gray regarding the enigmatic liana Dubautia latifolia.

evolutionary biology↗
bioRxiv2024

Viral susceptibility and innate immune competency of Carollia perspicillata bat cells produced for virological studies

Multiple viruses that are highly pathogenic in humans are known to have evolved in bats. How bats tolerate infection with these viruses, however, is poorly understood. As viruses engage in a wide range of interactions with their hosts, it is essential to study bat viruses in a system that resembles their natural environment like bat-derived in vitro cellular models. However, stable and accessible bat cell lines are not widely available for the broader scientific community. Here, we generated in vitro reagents for the Sebas short-tailed bat (Carollia perspicillata), tested multiple methods of immortalization, and characterized their susceptibility to virus infection and response to immune stimulation. Using a pseudotyped virus library and authentic virus infections, we show that these C. perspicillata cell lines derived from a diverse array of tissues are susceptible to viruses bearing the glycoprotein of numerous orthohantaviruses, including Andes and Hantaan virus and are also susceptible to live hantavirus infection. Furthermore, stimulation with synthetic double-stranded RNA prior to infection with VSV and MERS-CoV induced a protective antiviral response, demonstrating the suitability of our cell lines to study the bat antiviral immune response. Taken together, the approaches outlined here will inform future efforts to develop in vitro tools for virology from non-model organisms and these C. perspicillata cell lines will enable studies on virus-host interactions in bats.

microbiology↗
bioRxiv2024

Antiviral insulin signaling during West Nile virus infection results in viral mutations

Arthropod-borne viruses or arboviruses, including West Nile virus (WNV), dengue virus (DENV), and Zika virus (ZIKV) pose significant threats to public health. It is imperative to develop novel methods to control these mosquito-borne viral infections. We previously showed that insulin/insulin-like growth factor-1 signaling (IIS)-dependent activation of ERK and JAK-STAT signaling has significant antiviral activity. Continuous immune pressure can lead to adaptive mutations of viruses during infection. We aim to elucidate how IIS-signaling in mosquitoes selects for West Nile virus escape variants, to help formulate future transmission blocking strategies. We hypothesize that passage of WNV under activation of IIS will induce adaptive mutations or escape variants in the infecting virus. To test our hypothesis, WNV was serially passaged through Culex quinquefasciatus Hsu cells in the presence or absence of bovine insulin to activate IIS antiviral pressure. We sequenced WNV genes encoding for E, NS2B, NS3, and NS5 and identified variants in E and NS5 arising from IIS antiviral pressure. In parallel to the genetic analyses, we also report differences in the levels of virus replication and Akt activation in human cells using virus passaged in the presence or absence of insulin. Finally, using adult Culex quinquefasciatus, we demonstrated the enhancement of immune response gene expression in virus-infected mosquitoes fed on insulin, compared to control. Notably, virus collected from insulin-fed mosquitoes contained a non-synonymous mutation in NS3. These results contribute towards achieving our long-term goal of manipulating mosquito IIS-dependent antiviral immunity to reduce WNV or other flavivirus transmission to mammalian hosts.

immunology↗
bioRxiv2023

Insulin-mediated endothelin signaling is antiviral during West Nile virus infection

West Nile virus (WNV) is the most prevalent mosquito-borne virus in the United States with approximately 2,000 cases each year. There are currently no approved human vaccines and a lack of prophylactic and therapeutic treatments. Understanding host responses to infection may reveal potential intervention targets to reduce virus replication and disease progression. The use of Drosophila melanogaster as a model organism to understand innate immunity and host antiviral responses is well established. Previous studies revealed that insulin-mediated signaling regulates WNV infection in invertebrates by regulating canonical antiviral pathways. Because insulin signaling is well-conserved across insect and mammalian species, we sought to determine if results using D. melanogaster can be extrapolated for the analysis of orthologous pathways in humans. Here, we identify insulin-mediated endothelin signaling using the D. melanogaster model and evaluate an orthologous pathway in human cells during WNV infection. We demonstrate that endothelin signaling reduces WNV replication through the activation of canonical antiviral signaling. Taken together, our findings show that endothelin-mediated antiviral immunity is broadly conserved across species and reduces replication of viruses that can cause severe human disease. IMPORTANCEArboviruses, particularly those transmitted by mosquitoes, pose a significant threat to humans and are an increasing concern because of climate change, human activity, and expanding vector-competent populations. West Nile virus is of significant concern as the most frequent mosquito-borne disease transmitted annually within the continental United States. Here, we identify a previously uncharacterized signaling pathway that impacts West Nile virus infection, namely endothelin signaling. Additionally, we demonstrate that we can successfully translate results obtained from D. melanogaster into the more relevant human system. Our results add to the growing field of insulin-mediated antiviral immunity and identifies potential biomarkers or intervention targets to better address West Nile virus infection and severe disease.

microbiology↗
bioRxiv2020

A target enrichment probe set for resolving the flagellate plant tree of life

Premise of the studyNew sequencing technologies enable the possibility of generating large-scale molecular datasets for constructing the plant tree of life. We describe a new probe set for target enrichment sequencing to generate nuclear sequence data to build phylogenetic trees with any flagellate plants, comprising hornworts, liverworts, mosses, lycophytes, ferns, and gymnosperms. Methods and ResultsWe leveraged existing transcriptome and genome sequence data to design a set of 56,989 probes for target enrichment sequencing of 451 nuclear exons and non-coding flanking regions across flagellate plant lineages. We describe the performance of target enrichment using the probe set across flagellate plants and demonstrate the potential of the data to resolve relationships among both ancient and closely related taxa. ConclusionsA target enrichment approach using the new probe set provides a relatively low-cost solution to obtain large-scale nuclear sequence data for inferring phylogenetic relationships across flagellate plants.

evolutionary biology↗