Harnessing yeast to study APOL1 toxicity

APOL-1 protein plays a major role in Humans’ innate immune resistance to Trypanosomiasis by rapidly lysing infecting trypanosomes of the Trypanosoma brucei species endemic to Africa. In African descendant population, besides the G0 variant, two variants of APOL-1 protein are known: G1 (S342G, I384M) and G2 (deletion of N388 and Y389). Besides showing resistance to trypanosomal infection, these two variants are also associated with non-diabetic kidney disease. In recent years, the budding yeast, S. cerevisiae, has been proven as a powerful model organism for studying APOL-1 toxicity as expressing the disease-related APOL-1 variants results in higher toxicity relative to the G0 variant. The ability to easily manipulate the yeast cells genetic background allows detailed exploration of the underlying mechanisms that are responsible for this differential toxicity. In this work, we developed a high throughput screening apparatus that allow us to identify compounds that reduce the APOL-1 disease-related variants toxicity. Our results would facilitate our understanding of the molecular mechanisms that underlie APOL-1 toxicity and the discovery of potential therapies