Beach, S. | Search bioRxiv

bioRxiv2025

Heterologous expression of microbial nitroreductases for TNT degradation in transgenic animals

TNT (2,4,6-trinitrotoluene) from unexploded ordinances is a common environmental pollutant near munitions factories, military training sites, and areas of armed conflict. As physical and chemical approaches for TNT remediation are costly and difficult to scale, in situ bioremediation is an attractive alternative. TNT is a phytoaccumulative pollutant. Herbivores engineered to detoxify TNT are a potentially cost-effective platform to bioremediate large areas of contaminated sites while grazing or browsing. As a first step towards engineering herbivores with metabolic capabilities for TNT degradation, we engineered the animal genetic model, Drosophila melanogaster, to screen a library of microbial nitroreductases that can catalyse the initial degradation steps required for TNT degradation. We find strong, cofactor-dependent activity in fly lysates engineered to express NsfA from Escherichia coli, and NsfI from Enterobacter cloacae.

synthetic biology↗

bioRxiv2023

The brain's sensitivity to sensory error can be modulated by altering perceived variability

When individuals make a movement that produces an unexpected outcome, they learn from the resulting error. This process, essential in both acquiring new motor skills and adapting to changing environments, critically relies on error sensitivity, which governs how much behavioral change results from a given error. Although behavioral and computational evidence suggests error sensitivity can change in response to task demands, neural evidence regarding the flexibility of error sensitivity in the human brain is lacking. Critically, the sensitivity of the nervous system to auditory errors during speech production, a complex and well-practiced motor behavior, has been extensively studied by examining the prediction-driven suppression of auditory cortical activity. Here, we tested whether the nervous systems sensitivity to errors, as measured by this suppression, can be modulated by altering speakers perceived variability. Our results showed that error sensitivity was increased after exposure to an auditory perturbation that increased participants perceived variability, consistent with predictions generated from previous behavioral data and state-space modeling. Conversely, we observed no significant changes in error sensitivity when perceived variability was unaltered or artificially reduced. The current study establishes the validity of behaviorally modulating the nervous systems sensitivity to errors. As sensitivity to sensory errors plays a critical role in sensorimotor adaptation, modifying error sensitivity has the potential to enhance motor learning and rehabilitation in speech and, potentially, more broadly across motor domains. Significance StatementThe process of learning from error is essential for both the acquisition of new skills and successful adaptation to changing environments. Such error-based learning critically relies on error sensitivity, which determines how much we learn from a given error. Although evidence from behavioral studies suggests error sensitivity is malleable, neural evidence regarding the flexibility of error sensitivity in the human brain is lacking. Here, we showed that the nervous systems sensitivity to errors can be modulated by altering perceived variability. The present study establishes the validity of behaviorally modulating neural sensitivity to sensory errors. Improving our ability to learn from error can play a critical role in applied settings such as rehabilitation.

neuroscience↗