Biology subjects

Burgess, T.

Publications and source records attributed to Burgess, T..

6 recordsLinked to original sources

bioRxiv2026

Inter-population connectivity of southern elephant seals and the likely intra-species transmission pathways of high pathogenicity avian influenza

High Pathogenicity Avian Influenza (HPAI) H5N1 clade 2.3.4.4b has spread beyond birds to affect seals across the Southern Ocean and sub-Antarctic region, with southern elephant seals (Mirounga leonina) particularly devastated. The virus, likely introduced via spillover from infected migratory birds, has killed tens of thousands of adult seals and pups throughout most of their range, though Macquarie Island remains unaffected so far. We used twenty years of elephant seal movement data from the southern Indian and Pacific oceans to assess whether seal-to-seal transmission could spread HPAI H5N1 between breeding colonies, despite the vast distances separating them (Marion Island, Iles Crozet, Iles Kerguelen, and Macquarie Island). There was substantial overlap in seals at-sea distributions during their winter post-moult trips, when seals travel for weeks at average speeds of 3.5 km/h. Two transmission pathways were examined: (1) terrestrial "stepping stone" routes, where infected seals could pass the virus between colonies during short intervals to remain infectious were feasible from Marion Island to Kerguelen but not from Kerguelen to Macquarie Island; and (2) at-sea encounters between seals, which occurred frequently enough to enable transmission. The findings suggest that once established at Macquarie Island, the virus could potentially spread further to New Zealands sub-Antarctic islands and mainland New Zealand. While seal-to-seal transmission appears possible, we conclude this is unlikely. Nonetheless, understanding at-sea contact rates enhances knowledge of H5N1 epidemiology and demonstrates the value of combining long-term population monitoring with movement data to understand wildlife disease dynamics.

ecology↗

bioRxiv2026

Mass mortality of southern elephant seals during multi-species outbreak of HPAI H5N1 on sub-Antarctic Heard Island

High pathogenicity avian influenza (HPAI) has spread across the sub-Antarctic, causing significant wildlife impacts. We report its first detection in an Australian external territory, Heard Island and McDonald Islands, which supports over one million breeding seabirds and seals. Drone and ground surveys (October 2025, January 2026), combined with viral genome analysis, confirmed infection with Influenza A H5N1 clade 2.3.4.4b at Heard Island. Drone surveys revealed mass mortality in southern elephant seals, with 8,573 pups (62%) recorded dead across Heard Island by the final surveys. Mortality increased at an average rate of 5.6% per day in a subset of harems, and the highest observed mortality in a harem was 97%. Based on the average (76%) mortality in the final surveys, total estimated pup mortality at Heard Island was 13,359 (from a total population of 17,364 pups), though this may be an underestimate as mortality was ongoing at this time. HPAI was detected in six of nine species tested and, we suspect, led to elevated mortality in king and gentoo penguins. Phylogenetic analysis indicates the virus was introduced from Crozet Islands, with an estimated arrival around August 2025. These data show the continued easterly spread of HPAI around the sub-Antarctic, with severe but heterogeneous impacts across taxa. Our results demonstrate the value of drones for large-scale monitoring, underscoring the need for continued and enhanced HPAI surveillance across the Southern Ocean.

ecology↗

bioRxiv2023

LETHAL COVID-19 ASSOCIATES WITH RAAS-INDUCED INFLAMMATION FOR MULTIPLE ORGAN DAMAGE INCLUDING MEDIASTINAL LYMPH NODES

Lethal COVID-19 outcomes are most often attributed to classic cytokine storm and attendant excessive immune signaling. We re-visit this question using RNA sequencing in nasopharyngeal and 40 autopsy samples from COVID-19-positive and negative individuals. In nasal swabs, the top 100 genes which significantly correlated with COVID-19 viral load, include many canonical innate immune genes. However, 22 much less studied "non-canonical" genes are found and despite the absence of viral transcripts, subsets of these are upregulated in heart, lung, kidney, and liver, but not mediastinal lymph nodes. An important regulatory potential emerges for the non-canonical genes for over-activating the renin-angiotensin-activation-system (RAAS) pathway, resembling this phenomenon in hereditary angioedema (HAE) and its overlapping multiple features with lethal COVID-19 infections. Specifically, RAAS overactivation links increased fibrin deposition, leaky vessels, thrombotic tendency, and initiating the PANoptosis death pathway, as suggested in heart, lung, and especially mediastinal lymph nodes, with a tightly associated mitochondrial dysfunction linked to immune responses. For mediastinal lymph nodes, immunohistochemistry studies validate the transcriptomic findings showing abnormal architecture, excess fibrin and collagen deposition, and pathogenic fibroblasts. Further, our findings overlap findings in SARS-CoV-2 infected hamsters, C57BL/6 and BALB/c mouse models, and importantly peripheral blood mononuclear cell (PBMC) and whole blood samples from COVID-19 patients infected with early variants and later SARS-CoV-2 strains. We thus present cytokine storm in lethal COVID-19 disease as an interplay between upstream immune gene signaling producing downstream RAAS overactivation with resultant severe organ damage, especially compromising mediastinal lymph node function.

immunology↗

bioRxiv2023

Climate, host and geography shape insect and fungal communities of trees

Non-native pests, climate change, and their interactions are likely to alter relationships between trees and tree-associated organisms with consequences for forest health. To understand and predict such changes, factors structuring tree-associated communities need to be determined. Here, we analysed the data consisting of records of insects and fungi collected from dormant twigs from 155 tree species at 51 botanical gardens or arboreta in 32 countries. Generalized dissimilarity models revealed similar relative importance of studied climatic, host-related and geographic factors on differences in tree-associated communities. Mean annual temperature, phylogenetic distance between hosts and geographic distance between locations were the major drivers of dissimilarities. The increasing importance of high temperatures on differences in studied communities indicate that climate change could affect tree-associated organisms directly and indirectly through host range shifts. Insect and fungal communities were more similar between closely related vs. distant hosts suggesting that host range shifts may facilitate the emergence of new pests. Moreover, dissimilarities among tree-associated communities increased with geographic distance suggesting that human-mediated transport may facilitate the introductions of new pests. The results of this study highlight the need to limit the establishment of tree pests and increase the resilience of forest ecosystems to changes in climate.

ecology↗

bioRxiv2020

Genome-wide analyses of XRN1-sensitive targets in osteosarcoma cells identifies disease-relevant transcripts containing G-rich motifs.

XRN1 is a highly conserved exoribonuclease which degrades uncapped RNAs in a 5-3 direction. Degradation of RNAs by XRN1 is important in many cellular and developmental processes and is relevant to human disease. Studies in D. melanogaster demonstrate that XRN1 can target specific RNAs, which have important consequences for developmental pathways. Osteosarcoma is a malignancy of the bone and accounts for 2% of all paediatric cancers worldwide. 5 year survival of patients has remained static since the 1970s and therefore furthering our molecular understanding of this disease is crucial. Previous work has shown a downregulation of XRN1 in osteosarcoma cells, however the transcripts regulated by XRN1 which might promote osteosarcoma remain elusive. Here, we confirm reduced levels of XRN1 in osteosarcoma cell lines and patient samples and identify XRN1-sensitive transcripts in human osteosarcoma cells. Using RNA-seq in XRN1-knockdown SAOS-2 cells, we show that 1178 genes are differentially regulated. Using a novel bioinformatic approach, we demonstrate that 134 transcripts show characteristics of direct post-transcriptional regulation by XRN1. Long non-coding RNAs (lncRNAs) are enriched in this group suggesting that XRN1 normally plays an important role in controlling lncRNA expression in these cells. Among potential lncRNAs targeted by XRN1 is HOTAIR, which is known to be upregulated in osteosarcoma and contribute to disease progression. We have also identified G-rich and GU motifs in post-transcriptionally regulated transcripts which appear to sensitise them to XRN1 degradation. Our results therefore provide significant insights into the specificity of XRN1 in human cells which is relevant to disease.

molecular biology↗

bioRxiv2019

A Homogeneous SIRPα-CD47 Cell-Based, Ligand-Binding Assay: Utility for Small Molecule Drug Development in Immuno-oncology.

CD47 is an immune checkpoint protein that downregulates both the innate and adaptive anti-tumor immune response via its counter receptor SIRP. Biologics, including humanized CD47 monoclonal antibodies and decoy SIRP receptors, that block the SIRP-CD47 interaction, are currently being developed as cancer immunotherapy agents. However, adverse side effects and limited penetration of tumor tissue associated with their structure and large size may impede their clinical application. We recently developed a quantitative high throughput screening assay platform to identify small molecules that disrupt the binding of SIRP and CD47 as an alternative approach to these protein-based therapeutics. Here, we report on the development and optimization of a cell-based binding assay to validate active small molecules from our biochemical screening effort. This assay has a low volume, high capacity homogenous format that relies on laser scanning cytometry (LSC) and associated techniques to enhance signal to noise measurement of cell surface binding. The LSC assay is specific, concentration dependent, and validated for the two major human SIRP variants (V1 and V2), with results that parallel those of our biochemical data as well as published studies. The LSC assay also confirmed published studies, such as the inhibition of amino-terminal pyroglutamate formation in CD47 disrupts SIRP binding. SIRP-CD47 interaction could be quantitatively measured in live and fixed tumor cells. Use of fixed cells reduces the burden of cell maintenance and provides stable cell standards to control for inter- and intra-assay variations. We also demonstrate the utility of the assay to characterize the activity of the first reported small molecule antagonists of the SIRP-CD47 interaction. This assay will support the screening of thousands of compounds to identify or validate active small molecules as hits, develop structure activity relationships and assist in the optimization of hits to leads by a typical iterative medicinal chemistry campaign.

immunology↗