Abstract:
Diagnostics serve as the frontline defense for the containment and mitigation of infectious diseases. Significant effort has been made to develop G-coupled protein receptor (GPCR) based yeast biosensors for applications in drug discovery, environmental monitoring, and clinical diagnostics of small molecules and fungal pathogens. Yeast biosensors have exceptional advantages over other in vitro diagnostics that could lead to the next innovation for a low-cost, low-tech, reliable alternative in the point-of-care and at-home contexts including, long term storage in a reagent-free and dried dormant state, readily engineered with a colorimetric readout for positive/negative result, and rapidly scalable through industrial fermentation. In this talk, I will describe how GPCR-based yeast diagnostics function and can be developed for infectious fungal and viral pathogens. First, I will discuss the progress towards establishing a living yeast biosensor as a diagnostic for the pathogenic fungus Aspergillus fumigatus in clinical patient samples. Additionally, I will cover our efforts in the development of a yeast diagnostic for the multi-drug resistant fungus Candida auris to improve biosensing performance and validate the biomarker from clinical isolates. Finally, I will present engineered living yeast as a diagnostic tool for viral infections by tailoring the GPCR recognition element to sensing any amino-acid based biomarker of choice. Specifically, I will describe altering the binding specificity of the Scheffersomyces stipitis mating GPCR to detect the full-length SARS-CoV-2 Nucleocapsid protein via directed evolution.
