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2011 -
Grant Awardees - Program

How to build a kidney: quantitative modeling of kidney morphogenesis across time and space.

BYRNE Helen (UK)

Mathematical Institute - Oxford Centre for Collaborative Applied Mathematics - Oxford - UK


Murdoch Children's Research Institute - Royal Children's Hospital - Melbourne - AUSTRALIA


Dept. of Regenerative Medicine and Stem Cell Biology - The Broad-CIRM Center - Los Angeles - USA


Dept. of Anatomy and Developmental Biology - Monash Biomedicine Discovery Institute - Melbourne - AUSTRALIA

The kidneys are essential organs required for excretion of waste products and the regulation of fluid balance, blood pressure, blood volume, ion balance and bone density. The functional units of the kidney are the epithelial nephrons which can filter the entire blood volume every minute, creating 200 litres of filtrate each day and then recapturing 95% of this volume. All of the nephrons form during fetal development from two key stem/progenitor populations that interact with each other to form the intricately branched plumbing of the kidney as well as the filtering tubules. In humans, the number of nephrons per kidney varies 9 fold between individuals and there is an inverse correlation between nephron number and the likelihood of hypertension and kidney disease later in life. While much of kidney development has been described anatomically, due to a lack of quantitative and spatial modeling of this complex process across the fetal development, there is little understanding of how such variation in kidney size and nephron number can come about. The purpose of this application is to bring together mathematical modeling, advanced imaging and developmental genetics in order to develop a comprehensive model of the process of kidney development. Having created a framework that predicts the interactions between different cell types, we will test and refine this model by genetically altering the size of different cell populations to see how this affects development and whether the model holds. This will ultimately allow us to predict the outcome of perturbations in different cell compartments over space and time and potentially guide us with respect to understanding why nephron formation ends and what parameters might need to be altered to prolong the process.