Biology subjects

Fuller, J.

Publications and source records attributed to Fuller, J..

7 recordsLinked to original sources

bioRxiv2026

A Donor T-Cell Receptor Structural Signature Determines Alloreactive Potential and Predicts Acute Graft-Versus-Host Disease

Acute graft-versus-host disease (GVHD) remains a lethal barrier to successful allogeneic hematopoietic cell transplantation, yet pre-transplant donor selection entirely ignores hypervariable T-cell receptor (TCR) architecture. Here, by characterizing over 64,000 alloreactive clonotypes, we demonstrate that human alloreactivity is dictated by a constrained, predictable baseline structural signature. Pathogenic, tissue-infiltrating alloreactive T cells exhibit significantly shortened CDR3{beta} regions, altered antigen-facing biophysical features, biased VJ gene usage and extensive inter-donor sharing originating from public anti-pathogen memory reservoirs. These potent clones natively cluster within the high-frequency fraction of the unstimulated baseline donor repertoire. We introduce R50, an assay-independent metric quantifying this clonal dominance, which independently predicted a six-fold increased risk of acute GVHD in a cross-institutional cohort. This scalable in silico platform shifts pre-transplant risk stratification from HLA typing and demographic surrogates to precision immune-receptor modeling.

immunology↗

bioRxiv2025

Transcriptional response to Phytophthora root rot in raspberry identifies RiABP19, a Germin-like protein (GLP) gene with a putative role in resistance

Most phytophthora root rot (PRR) outbreaks in symptomatic commercially cultivated raspberry varieties are associated with the prevalence of Phytophthora rubi. Reduced availability of chemical actives and the persistent presence of Phytophthora oospores in the soil contribute to its devastating impact on raspberry-growing regions. In this study, we examined the variation in root morphology in two contrasting raspberry cultivars, Latham (PRR resistant) and Glen Moy (PRR susceptible). We performed RNA-sequencing on Latham roots challenged with P. rubi, to study the transcriptomic response and uncover mechanisms underpinning resistance. We established a new raspberry reference transcript dataset that allowed quantification of raspberry root gene expression. Transcripts significantly upregulated in Latham challenged with P. rubi, included many with characterised roles in resistance, such as Pathogenesis-related proteins and a Germin-like protein, designated RiABP19. The homologous Glen Moy RiABP19 gene showed no differential transcriptional response to PRR infection, indicating a resistance cultivar-specific induction signature following PRR challenge. Three-dimensional structural modelling predicts that RiABP19 contains conserved active sites implicated in auxin-binding and superoxide dismutase activity and can form a homo-hexamer like true germins. Co-immunoprecipitation assays confirmed that RiABP19 can form both homo- and heterodimers in planta. Virus-induced gene silencing of RiABP19 orthologs of in the model plant Nicotiana benthamiana strongly impacts immune signalling, enhancing Phytophthora infestans colonization and attenuating resistance and cell death triggered by the tomato Cf4/Avr4 interaction. These findings suggest that RiABP19 functions as a positive regulator of immunity and may represent a target for future crop improvement in raspberries.

plant biology↗

bioRxiv2023

An unconventional mechanism of IL-1β secretion that requires Type I IFN in lupus monocytes

Systemic Lupus Erythematosus (SLE) is characterized by autoreactive B cell activation, upregulation of Type I Interferon (IFN) and widespread inflammation. Mitochondrial nucleic acids (NAs) are increasingly recognized as triggers of IFN1. Thus, defective removal of mitochondria from mature red blood cells (Mito+ RBCs), a feature of SLE, contributes to IFN production by myeloid cells2. Here we identify blood monocytes (Mo) that have internalized RBCs and co-express IFN-stimulated genes (ISGs) and interleukin-1{beta} (IL-1{beta}) in SLE patients with active disease. We show that ISG expression requires the interaction between Mito+ RBC-derived mitochondrial DNA (mtDNA) and cGAS, while IL-1{beta} production entails Mito+ RBC-derived mitochondrial RNA (mtRNA) triggering of RIG-I-like receptors (RLRs). This leads to the cytosolic release of Mo-derived mtDNA that activates the NLRP3 inflammasome. Importantly, IL-1{beta} release depends on the IFN-inducible myxovirus resistant protein 1 (MxA), which enables the translocation of this cytokine into a trans-Golgi network (TGN)-mediated unconventional secretory pathway. Our study highlights a novel and synergistic pathway involving IFN and the NLRP3 inflammasome in SLE.

immunology↗

bioRxiv2021

BaRTv2: A highly resolved barley reference transcriptome for accurate transcript-specific RNA-seq quantification

Accurate characterization of splice junctions as well as transcription start and end sites in reference transcriptomes allows precise quantification of transcripts from RNA-seq data and enable detailed investigations of transcriptional and post-transcriptional regulation. Using novel computational methods and a combination of PacBio Iso-seq and Illumina short read sequences from 20 diverse tissues and conditions, we generated a comprehensive and highly resolved barley reference transcript dataset (RTD) from the European 2-row spring barley cultivar Barke (BaRTv2.18). Stringent and thorough filtering was carried out to maintain the quality and accuracy of the splice junctions and transcript start and end sites. BaRTv2.18 shows increased transcript diversity and completeness compared to an earlier version, BaRTv1.0. The accuracy of transcript level quantification, splice junctions and transcript start and end sites has been validated extensively using parallel technologies and analysis, including high resolution RT PCR and 5 RACE. BaRTv2.18 contains 39,434 genes and 148,260 transcripts, representing the most comprehensive and resolved reference transcriptome in barley to date. It provides an important and high-quality resource for advanced transcriptomic analyses, including both transcriptional and post-transcriptional regulation, with exceptional resolution and precision.

plant biology↗

bioRxiv2020

Single-dose replicating RNA vaccine induces neutralizing antibodies against SARS-CoV-2 in nonhuman primates

The ongoing COVID-19 pandemic, caused by infection with SARS-CoV-2, is having a dramatic and deleterious impact on health services and the global economy. Grim public health statistics highlight the need for vaccines that can rapidly confer protection after a single dose and be manufactured using components suitable for scale-up and efficient distribution. In response, we have rapidly developed repRNA-CoV2S, a stable and highly immunogenic vaccine candidate comprised of an RNA replicon formulated with a novel Lipid InOrganic Nanoparticle (LION) designed to enhance vaccine stability, delivery and immunogenicity. We show that intramuscular injection of LION/repRNA-CoV2S elicits robust anti-SARS-CoV-2 spike protein IgG antibody isotypes indicative of a Type 1 T helper response as well as potent T cell responses in mice. Importantly, a single-dose administration in nonhuman primates elicited antibody responses that potently neutralized SARS-CoV-2. These data support further development of LION/repRNA-CoV2S as a vaccine candidate for prophylactic protection from SARS-CoV-2 infection.

immunology↗

bioRxiv2020

Heritability estimates of antler and body traits in white-tailed deer (Odocoileus virginianus) from genomic-relatedness matrices

Estimating heritability (h2) is required to predict the response to selection and is useful in species that are managed or farmed using trait information. Estimating h2 in free-ranging populations is challenging due to the need for pedigrees; genomic-relatedness matrices (GRMs) circumvent this need and can be implemented in nearly any system where phenotypic and SNP data are available. We estimated the heritability of five body and three antler traits in a free-ranging population of white-tailed deer (Odocoileus virginianus) on Anticosti Island, Quebec, Canada. We generated GRMs from >10,000 SNPs: dressed body mass and peroneus muscle mass had moderate h2 values of 0.49 and 0.56, respectively. Heritability in male-only antler features ranged from 0.00 to 0.51 and had high standard errors. We explored the influence of minor allele frequency and data completion filters on h2: GRMs derived from fewer SNPs had reduced h2 estimates and the relatedness coefficients significantly deviated from those generated with more SNPs. As a corollary, we discussed limitations to the application of GRMs in the wild, notably how skewed GRMs increase variance around h2 estimates. This is the first study to estimate h2 on a free-ranging population of white-tailed deer and should be informative for breeding designs and management.

genomics↗

bioRxiv2019

BaRTv1.0: an improved barley reference transcript dataset to determine accurate changes in the barley transcriptome using RNA-seq

BackgroundTime consuming computational assembly and quantification of gene expression and splicing analysis from RNA-seq data vary considerably. Recent fast non-alignment tools such as Kallisto and Salmon overcome these problems, but these tools require a high quality, comprehensive reference transcripts dataset (RTD), which are rarely available in plants.\n\nResultsA high-quality, non-redundant barley gene RTD and database (Barley Reference Transcripts - BaRTv1.0) has been generated. BaRTv1.0, was constructed from a range of tissues, cultivars and abiotic treatments and transcripts assembled and aligned to the barley cv. Morex reference genome (Mascher et al., 2017). Full-length cDNAs from the barley variety Haruna nijo (Matsumoto et al., 2011) determined transcript coverage, and high-resolution RT-PCR validated alternatively spliced (AS) transcripts of 86 genes in five different organs and tissue. These methods were used as benchmarks to select an optimal barley RTD. BaRTv1.0-Quantification of Alternatively Spliced Isoforms (QUASI) was also made to overcome inaccurate quantification due to variation in 5 and 3 UTR ends of transcripts. BaRTv1.0-QUASI was used for accurate transcript quantification of RNA-seq data of five barley organs/tissues. This analysis identified 20,972 significant differentially expressed genes, 2,791 differentially alternatively spliced genes and 2,768 transcripts with differential transcript usage.\n\nConclusionA high confidence barley reference transcript dataset consisting of 60,444 genes with 177,240 transcripts has been generated. Compared to current barley transcripts, BaRTv1.0 transcripts are generally longer, have less fragmentation and improved gene models that are well supported by splice junction reads. Precise transcript quantification using BaRTv1.0 allows routine analysis of gene expression and AS.

genomics↗