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Biology subjects

Nguyen, D. X.

Publications and source records attributed to Nguyen, D. X..

2 recordsLinked to original sources

Using a GPT-5-driven autonomous lab to optimize the cost and titer of cell-free protein synthesis

We used an autonomous lab, comprising a large language model (LLM) and a fully automated cloud laboratory, to optimize the cost efficiency of cell-free protein synthesis (CFPS). By conducting iterative optimization, the LLM-driven autonomous lab was able to achieve a 40% reduction in the specific cost ($/g protein) of CFPS relative to the state of the art (SOTA). This cost reduction was accompanied by a 27% increase in protein production titer (g/L). Iterative experimental design, experiment execution, data capture and analysis, data interpretation, and new hypothesis generation were all handled by the LLM-driven autonomous lab. The interface between OpenAIs GPT-5 LLM and Ginkgo Bioworks cloud laboratory incorporated built-in validation checks via a Pydantic schema to ensure that AI-designed experiments were properly specified. Experimental designs were translated into programmatic specification of multi-instrument biological workflows by Ginkgos Catalyst software and executed on Ginkgos Reconfigurable Automation Cart (RAC) laboratory automation platform, with human intervention largely limited to reagent and consumables preparation, loading and unloading. By integrating LLMs with programmatic control of a cloud lab, we demonstrate that an LLM-driven autonomous lab can successfully perform a real-world scientific task, highlighting the potential of AI-driven autonomous labs for scientific advancement.

synthetic biology↗

Tumor Cell Clustering Enhances Metastatic Competence by Regulating the H3K36 Histone Demethylase KDM2A

Disseminated tumor cells can form clusters via cell-cell adhesion, which increases their capacity to initiate metastasis. Metastatic clusters are characterized by distinct changes in transcription, suggesting that epigenetic mechanisms underlie their unique phenotypic state. By performing functional epigenomic studies in models of non-small cell lung cancer, we identified the histone H3 lysine 36 (H3K36) demethylase KDM2A as being differentially required for the fitness of metastatic cell clusters. This contextual dependency on KDM2A is predicated by tumor cell-cell aggregation, which specifically induces KDM2A binding to CpG island enriched promoters. At these defined genomic loci, KDM2A maintains H3K36 monomethylation, which preferentially correlates with transcriptional activation. KDM2A directly targets oxidative phosphorylation genes and KDM2A activity is required for optimal mitochondrial respiration and apical cell junction integrity in cell clusters. Consequently, suppressing KDM2A reduces metastatic seeding and colonization in multiple organs, including in the brain. These findings reveal a chromatin regulatory mechanism by which homotypic cell communication instructs the epigenome of disseminated tumor cells to potentiate their metastatic competence.

cancer biology↗