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Biology subjects

Nichols, B.

Publications and source records attributed to Nichols, B..

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↗

Cysteine-S-nitrosylation inhibits Rop5-mediated immune evasion in Toxoplasma gondii

Reactive nitrogen species (RNS) are a mechanism to control microbial infections conserved across the host species of the obligate intracellular parasite Toxoplasma gondii. Cysteine S-nitrosylation (SNO) is a reversible post-translational modification that controls complex cell behaviors by regulating protein interactions and signal transduction events. Here we identified a cluster of T. gondii secreted effector proteins that are SNO-modified in a host inducible nitric oxide synthetase (iNOS)-dependent manner. Among these were the rhoptry protein 5 (ROP5) paralogs, which are the major virulence determinants in T. gondii and an immunodominant antigen in B6 mice. ROP5 was necessary for Type I and Type II parasites to evade IFN-{gamma}-mediated immune clearance in iNOS-deficient macrophages. RNS led to the loss of ROP5 association with the parasitophorous vacuole membrane, which is necessary for the known functions of ROP5. Infection with ROP5 knockout parasites rescued the susceptibility of iNOS-deficient mice to infection with Type II T. gondii. Together, these data indicate that RNS can promote cell-autonomous parasite clearance by inhibiting the function of ROP5 paralogs at the parasitophorous vacuole membrane. ImportanceRNS are necessary for cell-autonomous immunity to T. gondii infection; however, the molecular mechanisms by which RNS regulate parasite control remain poorly understood. Our findings support a model where post-translational modification of ROP5 by RNS is a conserved mechanism of inhibiting the functions of divergent ROP5 paralogs. These data provide a specific example of how host RNS are used to counter T. gondii immune evasion effectors that can be applied to understand how nitrosylation regulates the function of other parasite effectors and the role of RNS in the control of other intracellular pathogens.

microbiology↗