Biology subjects

Soanes, D. M.

Publications and source records attributed to Soanes, D. M..

7 recordsLinked to original sources

bioRxiv2025

Systemic infections alter cortical transcriptional signatures in Alzheimer's disease

Alzheimers disease (AD) is characterized by neuroinflammation, yet the impact of concurrent systemic infections on the AD brain remains poorly understood. We investigated the molecular mechanisms underlying the central nervous system response to systemic infections in AD by analyzing RNA sequencing data generated in the prefrontal cortex from 202 post-mortem donors (113 AD, 89 controls), where we stratified by the presence of a respiratory infection at the time of death. We identified 763 significantly differentially expressed genes (DEGs) between AD and controls without infection, which were enriched for oxidative phosphorylation and neurodegenerative pathways. In contrast, 122 DEGs distinguished AD from controls during infection, with 57 genes uniquely altered in AD in the presence of infection, including MAPK4, VAV3, and POU3F4, implicating infection-dependent mechanisms of vascular and immune regulation. Pathway activity analysis revealed that infection in AD suppresses some immune and vascular pathways, while enhancing transcriptional and developmental programs. Weighted gene co-expression network analysis uncovered three key modules: one module strongly associated with AD, enriched for aging and signal transduction; one module linked to both AD and infection, highlighting cytoskeletal remodelling and host-pathogen interactions; and one module specific to infection, enriched in astrocytes, pericytes, and endothelial cells, implicating blood-brain barrier dysfunction. These findings suggest that systemic respiratory infections reshape transcriptional programs in the AD brain, dampening immune effector pathways and engaging vascular and host-pathogen processes in blood-brain-barrier-associated cell types. Our results highlight the complex interplay between systemic infection, neuroinflammation, and vascular responses in AD.

neuroscience↗

bioRxiv2022

Rgs1 is a regulator of effector gene expression during plant infection by the rice blast fungus Magnaporthe oryzae

To cause rice blast disease the filamentous fungus Magnaporthe oryzae secretes a battery of effector proteins into host plant tissue to facilitate infection. Effector-encoding genes are expressed only during plant infection and show very low expression during other developmental stages. How effector gene expression is regulated in such a precise manner during invasive growth by M. oryzae is not known. Here, we report a forward-genetic screen to identify regulators of effector gene expression, based on selection of mutants that show constitutive effector gene expression. Using this simple screen, we identify Rgs1, a regulator of G-protein signalling (RGS) protein that is necessary for appressorium development, as a novel transcriptional regulator of effector gene expression, which acts prior to plant infection. We show that an N-terminal domain of Rgs1, possessing transactivation activity, is required for effector gene regulation and acts in an RGS-independent manner. Rgs1 controls expression of at least 60 temporally co-regulated effector genes, preventing their transcription during the pre-penetration stage of development prior to plant infection. A regulator of appressorium morphogenesis is therefore also required for orchestration of pathogen gene expression required for invasive growth by M. oryzae during plant infection.

molecular biology↗

bioRxiv2022

A pandemic clonal lineage of the wheat blast fungus

Wheat, the most important food crop, is threatened by a blast disease pandemic. Here, we show that a clonal lineage of the wheat blast fungus recently spread to Asia and Africa following two independent introductions from South America. Through a combination of genome analyses and laboratory experiments, we show that the decade-old blast pandemic lineage can be controlled by the Rmg8 disease resistance gene and is sensitive to strobilurin fungicides. However, we also highlight the potential of the pandemic clone to evolve fungicide-insensitive variants and sexually recombine with African lineages. This underscores the urgent need for genomic surveillance to track and mitigate the spread of wheat blast outside of South America, and to guide pre-emptive wheat breeding for blast resistance.

evolutionary biology↗

bioRxiv2020

A hierarchical transcriptional network controls appressorium-mediated plant infection by the rice blast fungus Magnaporthe oryzae

Rice blast is a pervasive and devastating disease that threatens rice production across the world. In spite of its importance to global food security, however, the underlying biology of plant infection by the blast fungus Magnaporthe oryzae remains poorly understood. In particular, it is unclear how the fungus elaborates a specialised infection cell, the appressorium, in response to surface signals from the rice leaf. Here, we report the identification of a network of temporally co-regulated transcription factors that act downstream of the Pmk1 mitogen-activated protein kinase pathway to regulate gene expression during appressorium-mediated plant infection. We have functionally characterised this network of transcription factors and demonstrated the operation of a hierarchical transcriptional control system. We show that this tiered regulatory mechanism involves Pmk1-dependent phosphorylation of the Hox7 homeobox transcription factor, which represses hyphal-associated gene expression and simultaneously induces major physiological changes required for appressorium development, including cell cycle arrest, autophagic cell death, turgor generation and melanin biosynthesis. Mst12 then regulates gene functions involved in septin-dependent cytoskeletal re-organisation, polarised exocytosis and effector gene expression necessary for plant tissue invasion.

microbiology↗

bioRxiv2018

A Genome-Wide Association Study Identifies SNP Markers for Virulence in Magnaporthe oryzae Isolates from Sub-Saharan Africa

The fungal phytopathogen Magnaporthe oryzae causes blast disease in cereals such as rice and finger millet worldwide. In this study, we assessed genetic diversity of 160 isolates from nine sub-Saharan Africa (SSA) and other principal rice producing countries and conducted a genome-wide association study (GWAS) to identify the genomic regions associated with virulence of M. oryzae. GBS of isolates provided a large and high-quality 617K single nucleotide polymorphism (SNP) dataset. Disease ratings for each isolate was obtained by inoculating them onto differential lines and locally-adapted rice cultivars. Genome-wide association studies were conducted using the GBS dataset and sixteen disease rating datasets. Principal Component Analysis (PCA) was used an alternative to population structure analysis for studying population stratification from genotypic data. A significant association between disease phenotype and 528 SNPs was observed in six GWA analyses. Homology of sequences encompassing the significant SNPs was determined to predict gene identities and functions. Seventeen genes recurred in six GWA analyses, suggesting a strong association with virulence. Here, the putative genes/genomic regions associated with the significant SNPs are presented.

genetics↗

bioRxiv2018

CRISPR-Cas9 ribonucleoprotein-mediated co-editing and counterselection in the rice blast fungus

The rice blast fungus Magnaporthe oryzae is the most serious pathogen of cultivated rice and a significant threat to global food security. To accelerate targeted mutation and specific gene editing in this species, we have developed a rapid plasmid-free CRISPR-Cas9-based gene editing method. It has previously been reported in M. oryzae that transformation with plasmids expressing Cas9 can generate specific mutations using sgRNAs, directing the endonuclease to specific genes. We show, however, that expression of Cas9 is highly toxic to M. oryzae, rendering this approach impractical. We demonstrate that using purified Cas9 pre-complexed to RNA guides to form ribonucleoproteins (RNPs), provides an alternative and very effective gene editing procedure. When used in combination with oligonucleotide or PCR-generated donor DNAs, generation of strains with specific base pair edits, in-locus gene replacements, or multiple gene edits, is very rapid and straightforward. Additionally, we report a novel counterselection strategy which allows creation of precisely edited fungal strains that contain no foreign DNA and are completely isogenic to the wild type. Together, these developments represent a scalable improvement in the precision and speed of genetic manipulation in M. oryzae and are likely to be broadly applicable to other fungal species.

microbiology↗

bioRxiv2018

The MoT3 assay does not distinguish between Magnaporthe oryzae wheat and rice blast isolates from Bangladesh

The blast fungus Magnaporthe oryzae is comprised of lineages that exhibit varying degrees of specificity on about 50 grass hosts, including rice, wheat and barley. Reliable diagnostic tools are essential given that the pathogen has a propensity to jump to new hosts and spread to new geographic regions. Of particular concern is wheat blast, which has suddenly appeared in Bangladesh in 2016 before spreading to neighboring India. In these Asian countries, wheat blast strains are now co-occurring with the destructive rice blast pathogen raising the possibility of genetic exchange between these destructive pathogens. We assessed the recently described MoT3 diagnostic assay and found that it did not distinguish between wheat and rice blast isolates from Bangladesh. The assay is based on primers matching the WB12 sequence corresponding to a fragment of the M. oryzae MGG_02337 gene annotated as a short chain dehydrogenase. These primers could not reliably distinguish between wheat and rice blast isolates from Bangladesh based on DNA amplification experiments performed in separate laboratories in Bangladesh and in the UK. In addition, comparative genomics of the WB12 sequence revealed a complex underlying genetic structure with related sequences across M. oryzae strains and in both rice and wheat blast isolates. We, therefore, caution against the indiscriminate use of this assay to identify wheat blast.

plant biology↗