Professor Kirill Alexandrov, NHMRC Investigator Fellow, Queensland University of Technology

Engineering of artificial  protein-based information processing systems

Allosteric regulation of proteins is referred to as the ‘second secret of life’ because it controls every aspect of information and energy processing in biology. As a result, the construction of artificial allosteric proteins that convert one type of biochemical signal into another is a central goal of synthetic biology.

We used structure-based protein engineering to construct artificial allosteric enzymes controlled by the input signals of choice. Switches based on light-emitting, electrochemically active, and antibiotic resistance-conferring enzymes require minimal optimisation and display dynamic responses up to 9000-fold. We demonstrate that machine learning-based protein design can be effectively integrated into the protein switch development pipeline and yield fully synthetic biosensors.

To demonstrate the utility of the constructed switches, we used them as the basis for ultra-low-cost diagnostic assays compatible with high-volume diagnostic workflows. We demonstrate detection of proteins and small molecules in human samples using standard chemical pathology equipment. Further we used protein switches with electrochemical output to construct sensory bio-electrodes that can convert analyte binding into electric current and enable construction of low-cost Point-of-Care diagnostic devices.