Introduction and Objectives: Nephrolithiasis is one of the most common renal diseases, but with poorly understood pathophysiology. The current understanding of how genetic, environmental, and metabolic factors act singly or in concert to trigger stone formation remains patchy, and the progress of medical therapy has been very modest. Vertebrate models for nephrolithiasis are limited in their ability to rapidly screen multiple and varied interventions that modulate urinary stone formation.

more »

... ore, we hypothesis that the basic research directed at model systems that elucidate the pathophysiology of stone disease is the best hope for advancing the field and leading to the development of new therapeutic approaches that have the potential to reduce the morbidity, mortality, and cost associated with this disease. Further, most studies have confounded that age and temperature share some contribution in precipitation of kidney stones. We also hypothesise that change in temperature (from colder to warmer, low temperature to higher temperature) may have a greater impact on the formation rate of nephrolithiasis. Methods: A short lifespan, rapid deployment of transgenic lines and conception of rapid stone formation makes Drosophila melanogaster an ideal system to screen large numbers of interventions to assess their effect on kidney stone formation. Knockdown of gene candidates for their ability to vary the formation of urinary stones was employed utilising Drosophila. Microdissection, imaging and quantification facilitate identification and collection of fly stones within the lumen of the Drosophila Malpighian tubules (the functional equivalent of the human renal tubule). Further, UAS-RNAi knockdown efficiency was validated by qPCR . The genes which upon knockdown modulated the concentration of accumulated stones were further studied using various genetic, immunostaining and molecular techniques. In addition to that I also identified role of temperature and age in kidney stone formation by rearing flies at 18, 22, 26 and [...]