Vladimir Zubkov

1. Mathematical Modelling of Kidney Morphogenesis. OCCAM PDRA Project

kidney Team leader: Professors Helen Byrne and Kevin Burrage.

Collaborators: Professor Melissa Little, University of Queensland, Australia; Professor Andy McMahon, University of South California, USA; Dr Ian Smyth, Monash University, Australia.


Background

Mammalian kidneys are vital organs that filter wastes such as urea from the blood and excrete them, with water, as urine. Kidney development is initiated by the outgrowth of a ureteric bud of epithelial cells into a population of mesenchymal cells. Interactions between the epithelial and mesenchymal cells coordinate the processes of cell proliferation and branching, leading to the formation of a highly branched structure known as the urinary collecting system. While models of fluid and solute transport within the mature kidney have been developed, little attention has been devoted to kidney morphogenesis. The main aim of this research project is to address this imbalance by developing new mathematical models of kidney morphogenesis.

Techniques and Challenges

The new mathematical models will be used to investigate the ways in which known biochemical and biophysical interactions between the epithelial and mesenchymal cells influence not only their rates of proliferation and differentiation but also the composition of the mature kidney (i.e. the total number of nephrons and its branching structure). The models can be informed by (and validated against) state-of-the-art data from normal and pathological kidneys that have been generated by our experimental collaborators (in Australia and the USA). In particular, we have access to (i) spatially-averaged, dynamic data showing how the number of ureteric tips and their sizes change over time and (ii) spatially-resolved images, collected using optical coherence tomography (OCT), of the developing kidney.

multiscale

References

V. Zubkov, K. Short, A. Combes, J. Lefevre, Adler Ju, K. Georgas, B. Rumballe, L. O'Brien, N. Hamilton, A.P. McMahon, I. Smyth, M. Little, H. Byrne, A spatially-averaged mathematical model of kidney morphogenesis, to be appear in JTB.


Melissa H. Little and Andrew P. McMahon: Mammalian Kidney Development: Principles, Progress, and Projections, Cold Spring Harb Perspect Biol, 2012