Biology subjects

Jones, E. L.

Publications and source records attributed to Jones, E. L..

4 recordsLinked to original sources

bioRxiv2025

Intracellular Trafficking SNARE Protein, Syntaxin-6, is a Modifier of Prion and Tau Pathogenesis in vivo and in Cellular Models

Syntaxin-6, a SNARE protein involved in intracellular protein trafficking, is a proposed risk factor for sporadic prion disease, progressive supranuclear palsy and Alzheimers disease. However, no study has validated its functional role in these diseases, explored the disease stage at which it is acting nor its mechanism of action. Here, we show that syntaxin-6 acts at early stages of prion disease in experimental mice by increasing disease transmission risk following inoculation with low prion doses. Conversely, syntaxin-6 does not affect prion propagation kinetics or toxicity during established disease. Syntaxin-6 manipulation in cellular models profoundly alters the subcellular distribution and morphologies of disease-related PrP and modifies prion export. Furthermore, syntaxin-6 knockout in a transgenic tauopathy mouse model exerts protective effects on numerous physiological, behavioural and neuropathological outcome measures. Therefore, our studies firmly establish syntaxin-6 as a modifier of prion and tau pathogenesis, providing key insights into a fundamental mechanism of neurodegeneration.

neuroscience↗

bioRxiv2024

Ocean carbon export can be predicted from ocean color-based phytoplankton communities

Carbon flux to the deep sea can be dictated by surface ocean phytoplankton community composition, but translating surface ocean observations into quantitative predictions of carbon export requires additional consideration of the underlying ecosystem drivers. Here, we used genetic tracers of phytoplankton detected in surface seawater and within sinking particles collected in the mesopelagic ocean to identify mechanistic links between surface communities and carbon export in the North Pacific and North Atlantic Oceans. Phytoplankton 18S rRNA sequences were sampled over a one-month period in surface seawater and within bulk-collected and individually-isolated sinking particles using mesopelagic sediment traps (100-500m). Nearly all phytoplankton amplicon sequence variants (ASVs) exported from the surface were packaged in large (>300 {micro}m) particles. Individually, these particles contained only a few distinct phytoplankton ASVs, but collectively, large particles transported about half of the surface taxonomic diversity into the mesopelagic. The relative sequence abundances of the surface community detected within particles were quantitatively related to measured POC fluxes: a linear model based on the relative sequence abundance of just two pigment-based phytoplankton taxa, diatoms and photosynthetic Hacrobia, was predictive of POC flux magnitude. These two taxa were also enriched within the ecologically-distinct particle classes that had the greatest influence on carbon export magnitude. As global, hyperspectral ocean color satellites begin to quantify these taxonomic groups in the surface ocean, the relationship of these taxa to carbon fluxes demonstrated here may help generate more accurate global estimates of export.

ecology↗

bioRxiv2024

Autoantigen TRIM21 (Ro52) assembles pro-inflammatory immune complexes following lytic cell death

Sjogrens disease (SjD) causes localised and systemic inflammation due to autoantibody production against intracellular proteins, such as TRIM21/Ro52. TRIM21 is an E3 ubiquitin ligase which binds antibody Fc domains on opsonised pathogens, which have escaped extracellular immunity and entered cytosols; TRIM21 ubiquitinates these, driving their proteasomal degradation. How and why TRIM21 becomes an autoantigen remains unclear. We show that TRIM21 is released upon lytic cell death (pyroptosis/necroptosis) but not apoptosis. Released TRIM21 binds circulating antibody Fc domains, and forms large immune complexes (ICs). These are further enhanced with TRIM21/Ro52 seropositive SjD plasma antibodies, where interactions are mediated via both Fc and F(ab)2 domains. TRIM21-ICs are taken up by macrophages, which in high interferon environments drive pro-inflammatory responses, antigen presentation, and inflammatory and metabolic transcriptional changes. Whilst many cytosolic proteins are released by dead cells, due to its high affinity for antibodies, TRIM21 can generate large ICs. This may perpetuate inflammation and antigen presentation, causing TRIM21 to be highly autoimmunogenic. One Sentence SummaryHow the intracellular protein TRIM21 becomes an autoantigen.

immunology↗

bioRxiv2023

Quantitative analysis of food web dynamics in a low export ecosystem

Food webs trace the flow of organic matter and energy among producers and consumers; for pelagic marine food webs, network complexity directly influences the amount and form of carbon exported to the deep ocean via the biological pump. Here we present a synoptic view of mixed layer food web dynamics observed during the late summer 2018 EXport Processes in the Ocean from Remote Sensing (EXPORTS) field campaign in the subarctic Northeast Pacific at the long-running time-series site, Ocean Station Papa. Carbon biomass reservoirs of phytoplankton, microzooplankton, and bacterioplankton, were approximately equal while mesozooplankton biomass was 70% lower. Live organisms composed [~]40% of the total particulate organic carbon within the mixed layer: the remainder was attributed to detritus. Rates of carbon transfer among reservoirs indicated production and assimilation rates were well balanced by losses, leaving little organic carbon available for export. The slight positive net community production rate generated organic carbon that was exported from the system in the form of food web byproducts, such as large fecal pellets generated by mesozooplankton. This characteristically regenerative food web had relatively slow turnover times with small-magnitude transfers of carbon relative to standing stocks that occurred amidst a high background concentration of detrital particles and dissolved organic matter. The concurrent estimation of food web components and rates revealed that separated processes dominated the transfer of carbon within the food web compared to those that contributed to export. Plain Language SummaryThe biological carbon pump drives a downward flux of organic matter from the sunlit surface ocean to the vast ocean interior. Ecological interactions in the surface ocean directly affect the amount and type of carbon that is exported to the deep ocean. In this study, we present a synthesis of the late summer mixed layer food web in the Northeast Pacific that was extensively characterized during the 2018 EXport Processes in the Ocean from Remote Sensing (EXPORTS) field campaign. We found the majority of carbon was recycled within the mixed layer by microbes through multiple transfers between producers and consumers. Larger organisms, mesozooplankton and salps, only consumed a small amount of carbon but through the formation of sinking fecal pellets were the main mechanism of transporting carbon out of the system. The study highlights the need to concurrently study microbial and large organism dynamics to develop a predictive understanding of the fate of organic carbon in the oceans. Key PointsO_LIThe microbial loop dominated carbon flow in the late summer mixed layer food web of the North Pacific, most net production was respired leaving little carbon available for export. C_LIO_LIActive production and consumption of organic carbon occurred amid a high background of detrital particulate organic carbon (58% of total) with slow turnover time, 66 d. C_LIO_LIMesozooplankton which had relatively minor carbon consumption rates created the majority of export production due to efficient repackaging of consumed material. C_LI

ecology↗