Biology subjects

Kosuri, P.

Publications and source records attributed to Kosuri, P..

4 recordsLinked to original sources

bioRxiv2026

Spatial imprints of emergent cardiomyocyte states in the pressure-overloaded heart

Resilience to cardiac stress is essential for health, yet the relationship between cardiomyocyte (CM) stress response and local microenvironment remains unclear. Here, we combined MERFISH spatial transcriptome profiling with Cellouette, an improved cell segmentation method, to determine CM-microenvironment relationships in a mouse model of ventricular pressure overload. We report the shape, transcription profile, spatial organization, and physical connectivity for >400,000 cells across stressed and healthy tissues. Under stress, CMs adopted a spectrum of emergent transcriptional states, with advanced states marked by a metabolic and pro-fibrotic shift. To discover CM-environment relationships, we performed a network analysis of physical cell connectivity combined with cell-type-specific profiling. We found that pro-fibrotic CM progression was tightly linked to distinct local microenvironments, and CM metabolic shifts could be inferred from transcriptional patterns in neighboring non-CM cells, revealing microenvironmental imprints of disease. We thus provide a resource for understanding the heterogeneity of outcome during cardiac pressure overload. HighlightsO_LICellouette provides accurate segmentation for single-cell spatial transcriptomics in cardiac tissue. C_LIO_LIPressure overload creates spatial gradients of cardiomyocyte pro-fibrotic states. C_LIO_LICardiomyocyte pro-fibrotic progression is linked to changes in local cell composition and gene expression. C_LIO_LITranscriptional states of non-muscle cells predict metabolic state of adjacent cardiomyocytes. C_LI

genomics↗

bioRxiv2026

Dye-cycling DNA origami rotors for long-term tracking of transcription at base-pair resolution

Protein interactions with DNA often result in rotational movements. These movements underlie many genetic processes such as DNA transcription by RNA polymerase (RNAP). To illuminate these movements, we previously developed Origami Rotor-Based Imaging and Tracking (ORBIT), a fluorescence-based method that enables high-speed tracking of DNA rotation. When used to track DNA rotation during transcription by E. coli RNAP, ORBIT enabled detection of single base-pair steps. However, the duration of ORBIT experiments was limited due to fluorescence photobleaching. To overcome this limitation and extend the total possible observation time, we here introduce dye-cycling ORBIT (dcORBIT), a method that enables observation of protein-DNA interactions for over 10 minutes at 20 Hz while maintaining single base-pair precision. dcORBIT thereby opens new possibilities to study the fundamental rotational movements underlying gene expression.

biophysics↗

bioRxiv2025

BellaVista: Open-Source Visualization for Imaging-Based Spatial Transcriptomics

Imaging-based spatial transcriptomics can reveal gene expression in situ by locating and identifying individual RNA molecules at subcellular resolution. These datasets typically contain an abundance of information that when analyzed appropriately can reveal tissue organization across scales from molecules to entire organs. However, there is currently a lack of simple open-source tools that facilitate visualization, quality control, and custom spatial analysis. Here we introduce BellaVista, a lightweight open-source tool for interactive visualization and exploration of imaging-based spatial transcriptomics data. BellaVista natively supports data from Xenium (10x Genomics), MERSCOPE (Vizgen), and custom MERFISH platforms. By providing a simple means for simultaneous visualization of images, transcripts, and cell segmentation boundaries, we anticipate that BellaVista will accelerate accessibility, exploration and discovery in the rapidly expanding field of spatial biology. BellaVista is available at https://github.com/pkosurilab/BellaVista.

bioinformatics↗

bioRxiv2023

NanoNERF: A nanoscale NERF blaster replica made of DNA

We used DNA origami to create NanoNERF, the worlds smallest NERF blaster replica (Figure 1). We based our design on the NERF model Maverick Rev-6, and scaled the dimensions down three million times. NanoNERF is planar and measures [~]100 nm in length, with a length-to-width ratio closely resembling the original toy. Here, we describe the design, prototyping, and validation pipeline used to create the NanoNERF. We also discuss potential applications to motivate the creation of future nanoscale blasters with a firing functionality. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=41 SRC="FIGDIR/small/560388v3_fig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@1d7619forg.highwire.dtl.DTLVardef@14a16dforg.highwire.dtl.DTLVardef@123b531org.highwire.dtl.DTLVardef@14cb703_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 1:C_FLOATNO A nanoscale replica of the NERF Maverick Rev-6 a) Original NERF Maverick Rev-6 toy, b) rendering of the NanoNERF structure in oxView. Gray lines represent individual DNA strands. NanoNERF length: 100 nm; width of barrel: 35 nm; thickness: 2 nm; c) Scan of a NanoNERF blaster acquired in an Atomic Force Microscope. C_FIG

biophysics↗