Being able to design ligand binding proteins is a fundamental challenge in biochemistry and synthetic biology. Bacterial chemoreceptors provide remarkable examples of protein-ligand recognition: they can detect chemicals at nanomolar concentrations and they can discriminate between closely related ligands. They play a central role in chemotaxis, allowing bacteria to detect chemical gradients and bias their swimming behaviour in order to navigate towards favourable environments.

There are thousands of chemoreceptor genes in bacterial genomes, but in spite of their importance, very few of the corresponding proteins have been characterised. This represents both an untapped source of protein-ligand pairs for decoding molecular recognition – and a vast array of ‘parts’ for use in synthetic biology.

We have begun to explore the structural and functional diversity of the chemoreceptors from Pseudomonas syringae pv. actinidiae (Psa). Psa is an important plant pathogen that is responsible for kiwifruit crop losses in New Zealand and throughout the world. Psa lives in a wide range of environments, including soil, water and plant tissues and has an unusually complex chemosensory system.

By using a new high-throughput screen, developed in my laboratory, we are characterising the complete chemosensory repertoire of Psa. Biophysical and structural characterization of the ligand binding domain (LBDs) of these receptors is providing insights into the structural basis of their molecular recognition. In addition, we are using directed evolution to generate LBDs with novel binding capabilities.

Together, these experiments are improving our understanding of how proteins selectively bind ligands, and how this process evolves. This understanding will facilitate the design of cells that  can localise to a specific chemical signal, such as a pollutant or a disease marker. Ultimately, these results will pave the way for construction of advanced biological systems that incorporate multiple functions, such as cells that can sense, seek out and remediate pollutants.