Mandracchia, B. | Search bioRxiv

bioRxiv2025

Real-time, High-throughput Super-resolution Microscopy via Panoramic Integration

We introduce super-resolution panoramic integration (SPI), an on-the-fly microscopy technique enabling instantaneous generation of subdiffractional images concurrently with scalable, high-throughput screening. SPI leverages multifocal optical rescaling, high-content sweeping, and synchronized line-scan readout while preserving minimal post-processing and compatibility with epi-fluorescence settings. We demonstrate SPI for various subcellular and populational morphology, function, and heterogeneity. This versatile platform offers a practical pathway toward biological insights beyond traditional optical and computational constraints.

bioengineering↗

bioRxiv2023

Metabolic and mitochondria alterations induced by SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10

Antiviral signaling, immune response and cell metabolism in human body are dysregulated by SARS-CoV-2, the causative agent of the COVID-19. Here, we show that SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10 induce a significant mitochondrial and metabolic reprogramming in A549 lung epithelial cells. While all four ORFs caused mitochondrial fragmentation and altered mitochondrial function, only ORF3a and ORF9c induced a marked structural alteration in mitochondrial cristae. ORF9b, ORF9c and ORF10 induced largely overlapping transcriptomes. In contrast, ORF3a induced a distinct transcriptome, including the downregulation of numerous genes for proteins with critical mitochondrial functions and morphology. Genome-Scale Metabolic Models predicted common and private metabolic flux reprogramming, notably a depressed amino acid metabolism, and an enhanced metabolism of specific lipids distinctly induced by ORF3a. These findings reveal metabolic dependencies and vulnerabilities prompted by SARS-CoV-2 accessory proteins that may be exploited to identify new targets for intervention. One-Sentence SummaryMitochondria and metabolic alterations induced by SARS- CoV-2 accessory proteins ORF3a, ORF9b, ORF9c, ORF10 in pulmonary cells unravel new targets of intervention.

immunology↗