Development of a Yeast-Based Biosensor for the Diagnosis and Routine Monitoring of Chronic Kidney Disease

My research addresses the need for an affordable diagnostic tool for chronic kidney disease in resource poor areas. Nearly 4 million lives are lost annually in resource-poor areas due to lack of early diagnoses and intervention. Chronic kidney disease (CKD), the 12th leading cause of death worldwide, is a significant, emerging burden in low and middle income countries where treatment is scarce. The levels of the peptide cystatin C in the body positively correlate with the severity of CKD. Cystatin C is typically measured with a nephelometer, which is expensive and requires substantial infrastructure. An affordable alternative is a yeast cell, which can naturally detect peptides. My goal is to develop a yeast-based diagnostic for cystatin C. Because yeast are low cost, retain viability after long storage times, and have well-studied, natural detection capabilities, I propose the development of a yeast-based biosensor for cystatin C. A yeast cell allows for the method of detection and output to be incorporated into one, portable device that could provide diagnostic results in less than two hours. Yeast naturally detect peptides with proteins called receptors, and I am altering one yeast receptor to respond to cystatin C. I have had success altering the yeast receptor to detect a peptide that is close to cystatin C. After the receptor has detected a peptide, yeast increase the expression of certain genes. Replacing one of these genes with one that causes the yeast cell to change color will yield a cystatin C biosensor with an output visible to the naked eye.