RAMONA
We built Ramona to advance human health through live imaging that delivers unrivaled precision and scale

Our goals


Understanding the behavioral and morphological dynamics of moving model organisms like the zebrafish larvae requires accurate, high-throughput 3D analysis. However, traditional single-view 2D video tracking fails to capture the full scope of natural 3D movements and postural dynamics. Here, we present a novel high-throughput 24-camera array microscope with a co-designed “mirrored well plate" that allows for snapshot imaging of up to 48 wells over a 118 mm × 82 mm field of view from two orthogonal directions (i.e., a top-view and side-view). Accurate 3D position estimation and tracking is achieved with an efficient machine learning algorithm that scales well to high-throughput measurements. The proposed approach automates parallelized 3D model organism behavioral analysis, providing 3D skeletal tracking, swim bladder morphological dynamics, and kinematics of up to 48 swimming zebrafish larvae at up to several hundred frames per second. The result is an efficient and scalable solution for high-throughput 3D behavioral studies with broad compatibility with standard workflows across laboratories and procedures working with pharmacology, toxicology, and neuroscience.
Aggression is a nearly universal behavior used to secure food, territory, and mates across species, including the fruit fly Drosophila melanogaster. In fruit flies, both sexes display aggression through stereotypical motor patterns. This, along with their sophisticated genetic and molecular toolkit, makes Drosophila melanogaster an excellent model for studying aggression. While male- and female-specific aggressive motor programs have been qualitatively described, automated systems for quantifying these behaviors in freely moving flies remain limited in their ability to combine high-resolution analysis with high throughput. Here, we pair a high-resolution, high-throughput imaging system (Kestrel) with DeepLabCut pose estimation to create a pipeline that tracks multiple freely moving fly pairs and quantifies social dynamics with high fidelity. We validated the system’s high-throughput performance and body-part tracking accuracy through manual scoring and established Drosophila behavioral phenotypes. The platform reliably reproduced a known phenotype: heightened female aggression following activation of cholinergic pC1 neurons. It also revealed a previously uncharacterized neuronal population labeled by R72A10-GAL4 that promotes courtship in males without affecting aggression. Pose-based analysis further detected locomotive differences between experimental and control groups, and subtle genotype-specific variations in aggression and courtship. By providing a high-fidelity readout of circuit-specific manipulations, this workflow enables mechanistic dissection of social behaviors.
G-quadruplexes (G4s) are four-stranded nucleic acid structures that regulate key cellular processes and represent promising therapeutic targets in oncology. To investigate the therapeutic potential of three G4 ligands—pidnarulex, APTO-253, and BRACO-19—a high-throughput drug combination screen was conducted in thirty-one multi-cell type tumor spheroids derived from patient tumors and established cancer cell lines. These 3D spheroids mimic key features of the tumor microenvironment, comprising malignant, endothelial, and mesenchymal cell populations. Compounds selected for combination screening included agents with mechanistic relevance to G4 biology, such as inhibitors of DNA damage response (DDR), replication stress, and chromatin regulation, based on the proposed roles of G4s in replication and genome stability. Combination responses were assessed using cell viability assays and supported by longitudinal brightfield imaging to monitor spheroid morphology and growth dynamics. Drug interactions were quantified using Bliss independence scores and the volume under the viability surface, providing complementary metrics of synergy and overall response. Among the G4 ligands, pidnarulex demonstrated the broadest single-agent activity, while APTO-253 and BRACO-19 showed limited effects. Model-specific synergy was observed from combinations with inhibitors of PARP, DDR kinases (ATM, ATR, DNA-PK), and cell cycle regulators (WEE1, PIM1). Interestingly, pidnarulex exhibited consistent synergy in one of eight pancreatic adenocarcinoma models (966289-007-R4-J1) across multiple DDR-targeted combinations. Combination interactions were also observed with HDAC inhibitors in a subset of models. Brightfield imaging corroborated enhanced spheroid growth suppression from synergistic combinations. These findings underscore the context-dependent activity of G4 ligands and support the use of integrated functional and imaging-based approaches to characterize potential therapeutic combinations in physiologically relevant 3D cancer models.
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