Professor
Kirill Alexandrov

Title: Machine Learning Meets Cross-Eyed Protein Engineering: Building Artificial Protein Switches

Allosteric regulation of proteins is often referred to as the “second secret of life” because it governs nearly every aspect of information and energy processing in biology. As a result, the construction of artificial allosteric proteins capable of converting one type of biochemical signal into another has become a central goal of synthetic biology.

We employed structure-based protein engineering to create artificial allosteric enzymes controlled by input signals of choice. Switches based on hydrolases, light-emitting enzymes, and redox enzymes required minimal optimisation and exhibited dynamic ranges of up to 9,000-fold. We further demonstrate that machine learning–based protein design can be effectively integrated into the protein switch development pipeline, enabling the generation of fully synthetic biosensors.

To evaluate the utility of the constructed switches, we employed them as the foundation for ultra-low-cost diagnostic assays compatible with high-throughput diagnostic workflows. We demonstrate the detection of proteins and small molecules in human samples using standard chemical pathology equipment. Furthermore, we utilised protein switches with electrochemical outputs to build sensory bioelectrodes capable of converting analyte binding into electric current, thereby enabling the development of low-cost point-of-care diagnostic devices.

Biography of the presenting author

Professor Kirill Alexandrov earned his Master’s in Invertebrate Zoology from Leningrad State University (1989) and a Ph.D. in Cell Biology from EMBL Heidelberg (1995). He conducted postdoctoral research at the Max-Planck Institute, becoming a group leader in 1999. In 2008, he joined the University of Queensland as an ARC Future Fellow and became a professor of synthetic biology at QUT in 2018. He co-founded JenaBioscience (1998), Molecular Warehouse (2015), and Cider Biotech (2024). His research focuses on artificial protein-based sensing and information processing systems.

Information

Prof Kirill Alexandrov,

NHMRC Investigator Fellow

ARC Centre of Excellence in Synthetic Biology

Queensland University of Technology

Gardens Point Campus

Brisbane, 4001,QLD,Australia

E: kirill.alexandrov@qut.edu.au