Biology subjects

Biela, A.

Publications and source records attributed to Biela, A..

5 recordsLinked to original sources

bioRxiv2026

Modular Surface Engineering of Feline Parvovirus Virus-Like Particles for Antigen Presentation and Receptor-Mediated Cell Targeting

Virus-like particles (VLPs) are non-infectious, multiprotein nanostructures that mimic the architecture of viruses while lacking genetic material. Their structural versatility and safety profile make them promising platforms for biomedical applications, including vaccine development, targeted drug delivery, and diagnostics. Among various functionalization strategies, click-chemistry has emerged as a precise and efficient method for attaching bioactive molecules to VLP surfaces. In this study, we report the production and functionalization of VLPs derived from the feline panleukopenia virus (FPV), a parvovirus closely related to the well-characterized canine parvovirus (CPV). We demonstrate successful expression, assembly, and purification of FPV VLPs, followed by their modification with fluorophores, peptides, oligonucleotides, and proteins using copper-free click-chemistry. Furthermore, using cryo-EM, we structurally characterize FPV VLP functionalized with antigenic peptides, providing detailed insights for further development of such vaccine prototype. Finally, we demonstrate that our FPV VLP specifically transduce feline and human cells expressing transferrin receptor type 1 (TfR), thus validating their potential as a unique platform for future nanotechnological and therapeutic applications.

bioengineering↗

bioRxiv2025

Pus7 mutation links tRNA dysregulation to aggressive behavior through activation of the integrated stress response and glycolytic reprogramming

Pseudouridine ({Psi}) is a prevalent RNA modification found in multiple RNA species. It is deposited by {Psi} synthases (Pus) and it can stabilize RNA structures. Patients carrying alterations in the Pus7 gene suffer from developmental delay, intellectual disability, microcephaly, hyperactivity and increased aggression levels. Here we show that the Pus7 mutation in human patient cells and in a Drosophila model is associated with a specific decrease of tRNA:Aspartate (tRNA-Asp) levels, which leads to slow decoding at Aspartate codons. This in turn activates the integrated stress response and induces a metabolic shift towards increased glycolysis and reduced mitochondrial respiration. Elevating tRNA-Asp expression, inhibiting the integrated stress response or dampening the glycolytic pathway is sufficient to rescue the aggressiveness phenotype, demonstrating the involvement of the tRNA-Asp-ISR-glycolysis axis in this behavior. Together our data provide new insights into the molecular defects associated with the loss of Pus7 and suggest potential new avenues for therapeutic treatment.

genetics↗

bioRxiv2024

Extended Plasmonic Nanostructures Templated by Tobacco Mosaic Virus Coat Protein

Optical and magnetic metamaterials possess interesting properties that cannot be achieved with conventional materials. However, there is currently no synthetic method offering both scalability and nanometer spatial precision. Biotemplating is a promising technique that has the potential to organize nanoscale components with high precision while being scalable and low-cost. Here we demonstrate a versatile template using hexahistidine-tagged tobacco mosaic virus coat protein. The protein self-assembles into disks which further assemble into extended nanostructures under mild conditions. Large sheets with either hexagonal or square packing and core-shell nanorods were formed, and gold nanoparticles were attached to the disks within each nanostructure to form assemblies of nanoparticle rings.

biochemistry↗

bioRxiv2024

Glycosaminoglycans act as activators of peptidylarginine deiminase 4

Peptidylarginine deiminase 4 (PAD4) is a citrullinating enzyme that is gathering increasing attention due to its possible involvement in physiological processes as well as in the pathogenesis of diseases like rheumatoid arthritis or thrombosis. PAD4 is activated by calcium ions, but the details of this mechanism are elusive, because in the human body, Ca2+ concentrations are too low for full activity. Given that glycosaminoglycans (GAGs) are also implicated in the development and progression of rheumatoid arthritis, we investigated the activation of PAD4 by GAGs using heparin as a model. We employed activity assays, chromatography techniques, molecular interaction measurements (MST and SPR), FACS, and immunocytochemistry to demonstrate the activation of PAD4 by GAGs. Our data show that PAD4 binds heparin with high affinity and forms high molecular weight complexes with heparin, consistent with heparin-bound tetramer formation. Heparin activates PAD4 by increasing the enzymes Ca2+ affinity threefold. We also show that the effectiveness of activation with heparin depends on the length of GAG used and its negative charge. Direct measurement of heparin binding to PAD4 confirmed tight interaction with nanomolar affinity. Mutagenesis of regions likely responsible for heparin binding showed that dimerization of PAD4 is necessary for efficient activation, but the distinct binding site was not determined as interaction with heparin likely occurs over larger surface of PAD4. Furthermore, we show that other GAG family members, including heparan and chondroitin sulphates, are also able to activate PAD4. We also found that disturbed production of GAGs by CHO cells results in reduced PAD4 binding efficiency. Finally, heparin induces NETosis in hPMNs in concentration-dependent manner, as measured by the release of DNA and citrullination of histone H3. In summary, we identify the first natural coactivator of PAD4, which is present in all individuals, potentially explaining the regulation of PAD4 activity in physiological conditions, and providing new insight into the development of rheumatoid arthritis and other PAD4-related diseases.

biochemistry↗

bioRxiv2021

Large scale screening discovers clofoctol as an inhibitor of SARS-CoV-2 replication that reduces COVID-19-like pathology

Drug repurposing has the advantage of shortening regulatory preclinical development steps. Here, we screened a library of drug compounds, already registered in one or several geographical areas, to identify those exhibiting antiviral activity against SARS-CoV-2 with relevant potency. Of the 1,942 compounds tested, 21 exhibited a substantial antiviral activity in Vero-81 cells. Among them, clofoctol, an antibacterial drug used for the treatment of bacterial respiratory tract infections, was further investigated due to favorable safety profile and pharmacokinetic properties. Notably, the peak concentration of clofoctol that can be achieved in human lungs is more than 20 times higher than its IC50 measured against SARS-CoV-2 in human pulmonary cells. This compound inhibits SARS-CoV-2 at a post-entry step. Lastly, therapeutic treatment of human ACE2 receptor transgenic mice decreased viral load, reduced inflammatory gene expression and lowered pulmonary pathology. Altogether, these data strongly support clofoctol as a therapeutic candidate for the treatment of COVID-19 patients. SummaryAntivirals targeting SARS-CoV-2 are sorely needed. In this study, we screened a library of drug compounds and identified clofoctol as an antiviral against SARS-CoV-2. We further demonstrated that, in vivo, this compound reduces inflammatory gene expression and lowers pulmonary pathology.

microbiology↗