The Development Of Novel Imaging Modalities & High-throughput Drug Screening Platforms In The Drosophila Melanogaster Model of Human Calcium Oxalate Nephrolithiasis
Abstract
Nephrolithiasis is a common urological disorder. Despite advances in the surgical treatment of kidney stone disease, research into its prevention and medical management remain stagnant. This is due to lack of viable pre-clinical models to study the disorder. In this project, we develop and characterize a robust Drosophila melanogaster model for human calcium oxalate nephrolithiasis. Using this model, we have developed intravital imaging techniques to study stone formation and novel high-throughput drug screening platforms. We successfully demonstrate calcium oxalate stone formation by sodium oxalate and ethylene glycol supplementation, with subsequent intravital imaging using bisphosphonate based fluorescent probes. Screening of 360 experimental compounds has revealed 6 compounds that inhibit calcium oxalate stone formation. We intend to further investigate the mechanism of action of these compounds, use them as a starting point for rational drug design and to develop Drosophila melanogaster models for other kidney stone types.