Project

Designing microbial whole-cell based biosensors for real-time monitoring of bioprocesses

Monitoring concentrations of compounds in bioreactors is crucial for maximising the efficiency of industrial bioprocesses. Prevalent methods for monitoring rely on sampling-based methods and measurements with bioreactor probes.

While the lack of bioreactor probes for complex compounds limits the variety of compounds that could be measured in real-time, sampling based methods require advanced equipment and fail to consider important parameters such as bioavailability and heterogeneous spatial distribution. SENSIBAR project aims to tackle this issue by developing last-generation living biosensors that measure the compounds of interest in bioreactors in real-time. Integration of microbial whole-cell based biosensors in biosensor device will provide novel means to real-time monitoring of bioprocesses.

Background

Whole-cell biosensors harness the natural capacity of living cells to sense specific target molecules in their environment, and trigger metabolic and cellular responses accordingly. Advancements in synthetic biology provide a wide range of tools for design of novel biosensing systems and fine-tuning of biosensor properties. In this project, we will not only leverage the existing synbio toolbox for creating novel biosensors, but we will also develop novel post-transcriptional control mechanisms and explore the integration of genetic circuits for improved sensing. Moreover, we aim to establish a modular platform for generation of novel biosensors, facilitating the design of tailor-made biosensors for applications ranging from strain screening to real-time bioprocess monitoring.

Project description

  • Design of novel chimeric sensor proteins and two-component systems for measurement of extracellular signals (computational modelling of new to nature chimeric proteins)
  • Design of Experiments (DoE) for improved signal transduction
  • Förster resonance energy transfer (FRET)-based biosensors
  • Fine-tuning signal transduction for the optimization of biosensor output (phosphatase/kinase ratio tuning, sequestration by non-cognate response regulators, genetic circuits)
  • High throughput generation and screening of microbial whole-cell biosensors (growth-coupled screening, adaptive lab evolution)
  • Integration of riboregulators such as self-splicing introns and toehold switches, and CRISPR cascades for improved output generation