Biology subjects

Choi, D.-H.

Publications and source records attributed to Choi, D.-H..

3 recordsLinked to original sources

bioRxiv2025

A community-consensus reconstruction of Chinese Hamster metabolism enables structural systems biology analyses to decipher metabolic rewiring in lactate-free CHO cells

Genome-scale metabolic models (GEMs) are indispensable for studying and engineering cellular metabolism. Here, we present iCHO3K, a community-consensus, manually-curated reconstruction of the Chinese Hamster metabolic network. In addition to accounting for 11004 reactions associated with 3597 genes, iCHO3K includes 3489 protein structures and structural descriptors for >70% of its 7377 metabolites, enabling deeper exploration of the link between molecular structure and cellular metabolism. We used iCHO3K to contextualize transcriptomics and metabolomics data from a CHO cell line in which lactate secretion is abolished. We found the reduced glycolytic flux and enhanced TCA cycle flux were accompanied by an elevated NADH and PEP levels in these cells, consistent with experimental measurements. Leveraging iCHO3Ks structural annotations, we identified candidate binding interactions of NADH and PEP with glycolytic enzymes showing model-predicted differential flux, suggesting novel allosteric regulation associated with the observed decrease in glucose uptake and glycolysis. Overall, iCHO3K offers a valuable framework for systematic integration of omics data, improved flux predictions, and structure-guided insights, thus advancing CHO cell engineering and enhancing biomanufacturing efficiency.

systems biology↗

bioRxiv2024

SARS-CoV-2 infection activates inflammatory macrophages in vascular immune organoids

SARS-CoV-2 provokes devastating tissue damage by cytokine release syndrome and leads to multi-organ failure. Modeling the process of immune cell activation and subsequent tissue damage is a significant task. Organoids from human tissues advanced our understanding of SARS-CoV-2 infection mechanisms though, they are missing crucial components: immune cells and endothelial cells. This study aims to generate organoids with these components. We established vascular immune organoids from human pluripotent stem cells and examined the effect of SARS-CoV-2 infection. We demonstrated that infections activated inflammatory macrophages. Notably, the upregulation of interferon signaling supports macrophages role in cytokine release syndrome. We propose vascular immune organoids are a useful platform to model and discover factors that ameliorate SARS-CoV-2-mediated cytokine release syndrome.

immunology↗

bioRxiv2023

Debottlenecking and reformulating feed media for improved CHO cell growth and titer by data-driven and model-guided analyses

Designing and selecting cell culture media and feed are a key strategy to maximize culture performance in industrial biopharmaceutical processes. However, this is a major challenge for therapeutic proteins production since mammalian cells are very sensitive to their culture environment and require specific nutritional needs to grow and produce high-quality proteins such as antibodies. In this regard, in our previous study, we developed data-driven and in-silico model-guided systematic framework to investigate the effect of growth media on Chinese hamster ovary (CHO) cell culture performance, allowing us to design a new media formulation. To expand our exploration to feed, in this study, we evaluated two chemically defined feed media, A and B, in Ambr15 bioreactor runs using a monoclonal antibody-producing CHO K1 cell line. The feeds had a significant impact on cell growth, longevity, viability, and productivity and toxic metabolites production. Specifically, concentrated feed A was not sufficient to support prolonged cell culture and high titer compared to feed B. The framework systematically characterized the major metabolic bottlenecks in the TCA cycle and its related amino acid transferase reactions, and identified key design components, such as asparagine, aspartate, and glutamate, needed for highly productive cell cultures. From our results, we designed three new feeds by adjusting the levels of those amino acids and successfully validated their effectiveness in promoting cell growth and/or titer.

bioengineering↗