Biology subjects

Rossius, J.

Publications and source records attributed to Rossius, J..

4 recordsLinked to original sources

bioRxiv2026

Tau spreading coordinates intercellular lipid flux enhancing neuronal resilience to lipid toxicity

The presence of intrinsically disordered proteins (IDPs) in the extracellular environment of the brain suggests that protein disorder may serve functions beyond those confined to the intracellular space. Tau, a prototypical IDP linked to tauopathies, a class of neurodegenerative diseases, is continuously released and spreads between cells in the brain, yet the biological significance of this extracellular phase remains unresolved. Here, we show that spreading tau coordinates neutral lipid homeostasis by promoting neuronal lipid efflux and enhancing resilience to lipid toxicity. Integrating transcriptomics and lipidomics, we demonstrate that tau spreading reprograms lipid transport pathways and triggers redistribution of triacylglycerol pools, remodeling neutral lipid metabolism. Mechanistically, cellular uptake of spreading tau drives its accumulation within neutral lipid-rich compartments and promotes neuronal lipid efflux. The exported lipids are enriched in peroxidized species that are subsequently transferred to astrocytes, reducing neuronal lipid stress and revealing a pathway through which tau regulates lipid homeostasis. Our findings reframe spreading tau as a regulator of intercellular lipid flux and position protein disorder as an active mediator of cell-to-cell communication in coordinating tissue metabolism. Loss of this homeostatic function is likely to contribute to the early metabolic dysfunction associated with tauopathy.

neuroscience↗

bioRxiv2026

Spreading α-synuclein rewires organelle communication and impairs neuron-astrocyte mitochondrial quality control

Progressive intercellular spreading of -synuclein (S) is implicated in pathology initiation and propagation of synucleinopathies. However, how recipient neurons respond to incoming S and whether these responses contribute to disease-associated early metabolic events, remains unknown. Here, using extracellular monomeric S to model the earliest cellular response to spreading, we found that internalized S accumulates at tri-organelle contact sites linking mitochondria, endoplasmic reticulum, and endo/lysosomal compartments. At these interfaces, S stabilizes generally dynamic contacts and constrains their remodeling, thereby rewiring organelle communication. These effects require the acidic S C-terminus and are not recapitulated by intracellular S overexpression. Proteomic profiling of S-associated mitochondria identified a contact site-enriched but quality-control-deficient state. Functionally, spreading S impairs neuron-astrocyte mitochondrial quality control (MQC) by reducing neuronal mitochondria transfer to astrocytes, while enhancing mitochondrial import. Our findings establish organelle contact sites as critical target of spreading S, through which rewired organelle communication impairs MQC and neuron-astrocyte crosstalk.

neuroscience↗

bioRxiv2026

Novel mouse reporter models for the detection of genome editing events in vivo

With the expansion of therapeutic gene editing technology, small animal models provide essential platforms to evaluate the function of these new approaches in vivo. As part of the Somatic Cell Genome Editing (SCGE) Consortium, we developed next-generation murine reporters that overcome current model limitations and broaden detectable in vivo editing outcomes. These include two mouse models built on the "traffic light" reporter concept. This system enables fluorescent detection of both gene repair (green) and CRISPR-generated indels (red) events following editing by a single guide and either dsDNA or single-stranded oligonucleotide donor. We also generated a third reporter model that efficiently detects A-base editor activity. Reporters were validated in cultured embryos, via germline editing, and through activation in vivo by AAV transduction or direct ribonucleoprotein delivery. Together, these new models provide a valuable resource for improved detection of genome editing events in vivo.

genomics↗

bioRxiv2026

A bio-orthogonal and covalent 5 kDa small protein tag

Precise and minimally perturbative protein labelling remains a key challenge for studying biomolecular function in living systems. Here, a minimal way to specifically label proteins based on SNAP-tag and intein-mediated protein splicing reaction is introduced. Termed CLUSTER (for Chemical Label-Unfold-Splice Technology Enables Recombination), this chimeric platform supports efficient labelling across diverse targets in living cells by retaining a fluorescent, 5 kDa sized peptide on a fusion protein of interest after splicing. A bacterial screening workflow was developed to optimize the reaction efficiency and construct design. Quantitative characterization using fluorescence polarization provides mechanistic insight into labelling efficiency and dynamics, while molecular dynamics simulations elucidate its stability, grasping the intricate nature of protein behaviour upon covalent labelling. This bio-orthogonal labelling technology allows for a versatile and minimally invasive approach for protein labelling, providing a powerful tool to probe protein behavior in native cellular systems.

synthetic biology↗