Biology subjects

Cordes, E.

Publications and source records attributed to Cordes, E..

6 recordsLinked to original sources

bioRxiv2026

TRAPPC8 Is an Endogenous Brake on UFMylation That Suppresses Tauopathy

UFMylation, a ubiquitin-like protein modification, drives tau spread through the brain, but what keeps this process in check has remained unclear. We show that TRAPPC8 acts as a natural brake on UFMylation, binding directly to the E1 enzyme UBA5 to dampen pathway activity. In Alzheimer's disease brain tissue, TRAPPC8 is reduced while UFMylation is elevated, suggesting this brake fails as disease progresses. Sustaining UFMylation in human iPSC-derived neurons increased tau aggregation and spread while disrupting lysosomal function and lipid balance. Restoring TRAPPC8-UBA5 binding reversed these defects through the lysosomal protein CLN8, which restored lysosomal function and reduced tau pathology. Notably, expressing just the UBA5-binding region of TRAPPC8 was enough to suppress tau pathology in vivo, marking it as a promising therapeutic target.

neuroscience↗

bioRxiv2026

Humanized tauopathy chimeras uncover microglial and lncRNA strategies for neuroprotection

Human genetics implicates innate immunity as a key modifier of tau toxicity, yet human-specific neuroimmune mechanisms remain difficult to test in vivo. Here, we developed HuMiNAX, the first humanized iPSC-based neuroimmune xenograft model of tau-associated neurodegeneration, enabling human microglia to interact with human neurons and astrocytes in the adult mouse brain. In HuMiNAX, tau seeding induced aggregation only in mutation-carrying human neural grafts, causing neuron loss and inflammatory activation of human microglia. Progranulin-overexpressing human microglia dampened tau-associated inflammation, preserved neurons, and restored neuronal gene-expression and RNA-splicing programs, supporting microglial control of neuronal resilience. CRISPRi knockdown of the human-specific lncRNA HNRNPK-AS1 also protected neurons in HuMiNAX. These findings establish HuMiNAX as a human neuroimmune model of tauopathy and identify microglial and RNA-mediated strategies of neuronal resilience.

neuroscience↗

bioRxiv2026

Novel insights into conserved biomineralization mechanisms revealed from a cold-water scleractinian coral skeletal proteome

Stony corals exhibit striking morphological plasticity across diverse environments and trophic strategies, raising fundamental questions about the conservation of their biomineralization machinery. Here, we characterize the skeletal organic matrix proteome of the cold-water, asymbiotic coral Desmophyllum pertusum and compare it with skeletal proteomes from a facultatively photosymbiotic temperate coral and an obligately photosymbiotic subtropical coral. Despite pronounced differences in habitat, symbiotic status, and skeletal micro-density, we observe convergence on a conserved "biomineralization toolkit". Comparative proteomics, genomics, and structural predictions reveal that this toolkit integrates diverse acidic matrix proteins, carbonic anhydrases, adhesion and structural proteins, and signaling components with multiple cellular export pathways. Together, these findings redefine coral biomineralization as a dynamic, coordinated network of cellular pathways rather than a static assemblage of matrix components. The symbiont-free model D. pertusum provides a mechanistic framework for dissecting coral calcification across environments and for assessing the resilience of this conserved machinery.

biochemistry↗

bioRxiv2023

Genome assembly of the deep-sea coral Lophelia pertusa

Like their shallow-water counterparts, cold-water corals create reefs that support highly diverse communities, and these structures are subject to numerous anthropogenic threats. Here, we present the genome assembly of Lophelia pertusa from the southeastern coast of the USA, the first one for a deep-sea scleractinian coral species. We generated PacBio CLR data for an initial assembly and proximity ligation data for scaffolding. The assembly was annotated using evidence from transcripts, proteins, and ab initio gene model predictions. This assembly is comparable to high-quality reference genomes from shallow-water scleractinian corals. The assembly comprises 2,858 scaffolds (N50 1.6 Mbp) and has a size of 556.9 Mbp. Approximately 57% of the genome comprises repetitive elements and 34% of coding DNA. We predicted 41,089 genes, including 91.1% of complete metazoan orthologs. This assembly will facilitate investigations into the ecology of this species and the evolution of deep-sea corals.

genomics↗

bioRxiv2020

Fungal communities in sediments along a depth gradient in the Eastern Tropical Pacific

Deep waters represent the largest biome on Earth and the largest ecosystem of Costa Rica. Fungi play a fundamental role in global biogeochemical cycling in marine sediments, yet, they remain little explored. We studied fungal diversity and community composition in several marine sediments from 16 locations sampled along a bathymetric gradient (from a depth of 380 to 3474 m) in two transects of about 1500 km length in the Eastern Tropical Pacific (ETP) of Costa Rica. Sequence analysis of the V7-V8 region of the 18S rRNA gene obtained from sediment cores revealed the presence of 787 fungal amplicon sequence variants (ASVs). On average, we detected a richness of 75 fungal ASVs per sample. Ascomycota represented the most abundant phylum with Saccharomycetes constituting the dominant class. Three ASVs accounted for ca. 63% of all fungal sequences: the yeast Metschnikowia (49.4%), Rhizophydium (6.9%), and Cladosporium (6.7%). Although we distinguished a cluster dominated by yeasts and a second cluster dominated by filamentous fungi, we were unable to detect a strong effect of depth, temperature, salinity, dissolved oxygen, and pH on the composition of fungal communities. We highlight the need to understand further the ecological role of fungi in deep-sea ecosystems.

microbiology↗

bioRxiv2019

Sequestration of Methane by Symbiotic Deep-Sea Annelids: Ancient and Future Implications of Redefining the Seep Influence

Deep-sea methane seeps are dynamic sources of greenhouse gas production and unique habitats supporting ocean biodiversity and productivity. Here, we demonstrate new animal-bacterial symbioses fueled by methane, between two undescribed species of annelid (a serpulid Laminatubus and sabellid Bispira) and distinct methane-oxidizing Methylococcales bacteria. Worm tissue {delta}13C of -44{per thousand} to -58{per thousand} suggested methane-fueled nutrition for both species and shipboard experiments revealed active assimilation of 13C-labelled CH4 into animal biomass, occurring via engulfment of methanotrophic bacteria across the host epidermal surface. These worms represent a new addition to the few animals known to intimately associate with methane-oxidizing bacteria, and further explain their enigmatic mass occurrence at 150-million-year-old fossil seeps. High-resolution seafloor surveys document significant coverage by these symbioses, beyond typical obligate seep fauna. These findings uncover novel consumers of methane in the deep-sea, and by expanding the known spatial extent of methane seeps, may have important implications for deep-sea conservation.

microbiology↗