Dr. Pamela Peralta-Yahya (School of Chemistry and Biochemistry)

Committee:  

Dr. James C. Gumbart (School of Physics, Georgia Institute of Technology)  

Dr. John Blazeck (School of Chemical and Biomolecular Engineering, Georgia Institute of Technology)

Dr. Andrew McShan (School of Chemistry and Biochemistry, Georgia Institute of Technology)

Dr. Corey Wilson (School of Chemical and Biomolecular Engineering, Georgia Institute of Technology)

Improving signal transduction of human GPCRs via yeast machinery.

G-Protein coupled receptors, or GPCRs, are a highly druggable class of human receptors. They constitute one of the largest and most versatile families of membrane protein that translate external stimuli into intracellular responses. This ability to detect a diverse set of ligands makes them an integral part of human pharmacology. About 30% of FDA-approved drugs target GPCR mediated pathways. They can be heterologously expressed in systems like Saccharomyces cerevisiae to develop a fast, engineerable high-throughput biosensors capable of detecting receptor-ligand interactions with applications in drug discovery and development. However, functional expression of human GPCRs in yeast, a non-native chassis, remains challenging often due to inefficient signal transduction via yeast machinery. This thesis addresses this challenge and expands the utility of yeast-based GPCR biosensors by improving GPCR-GPA1 coupling.