Inferring Gene Regulatory Neural Networks for Bacterial Decision Making in Biofilms

Bacterial cells are sensitive to a range of external signals used to learn the environment. These incoming external signals are then processed using a Gene Regulatory Network (GRN), exhibiting similarities to modern computing algorithms. An in-depth analysis of gene expression dynamics suggests an inherited Gene Regulatory Neural Network (GRNN) behavior within the GRN that enables the cellular decision-making based on received signals from the environment and neighbor cells. In this study, we extract a sub-network of \textit{Pseudomonas aeruginosa} GRN that is associated with one virulence factor: pyocyanin production as a use case to investigate the GRNN behaviors. Further, using Graph Neural Network (GNN) architecture, we model a single species biofilm to reveal the role of GRNN dynamics on ecosystem-wide decision-making. Varying environmental conditions, we prove that the extracted GRNN computes input signals similar to natural decision-making process of the cell. Identifying of neural network behaviors in GRNs may lead to more accurate bacterial cell activity predictive models for many applications, including human health-related problems and agricultural applications. Further, this model can produce data on causal relationships throughout the network, enabling the possibility of designing tailor-made infection-controlling mechanisms. More interestingly, these GRNNs can perform computational tasks for bio-hybrid computing systems.

Microfluidic-based Bacterial Molecular Computing on a Chip

Biocomputing systems based on engineered bacteria can lead to novel tools for environmental monitoring and detection of metabolic diseases. In this paper, we propose a Bacterial Molecular Computing on a Chip (BMCoC) using microfluidic and electrochemical sensing technologies. The computing can be flexibly integrated into the chip, but we focus on engineered bacterial AND Boolean logic gate and ON-OFF switch sensors that produces secondary signals to change the pH and dissolved oxygen concentrations. We present a prototype with experimental results that shows the electrochemical sensors can detect small pH and dissolved oxygen concentration changes created by the engineered bacterial populations' molecular signals. Additionally, we present a theoretical model analysis of the BMCoC computation reliability when subjected to unwanted effects, i.e., molecular signal delays and noise, and electrochemical sensors threshold settings that are based on either standard or blind detectors. Our numerical analysis found that the variations in the production delay and the molecular output signal concentration can impact on the computation reliability for the AND logic gate and ON-OFF switch. The molecular communications of synthetic engineered cells for logic gates integrated with sensing systems can lead to a new breed of biochips that can be used for numerous diagnostic applications.