BB26: Mathematical modelling of kidney morphogenesis
| Researcher: | Dr Vladimir Zubkov |
| Team Leader(s): | Prof. Helen Byrne |
| Collaborators: | Prof. Melissa Little, University of Queensland |
| Prof. Andy McMahon, University of South California | |
| Dr Ian Smyth, Monash University |
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.
The Future
Mathematical modelling will be used to investigate the ways in which known biochemical and biophysical interactions between the epithelial and mesenchymal cells influence the final structure of the kidney. The models will be validated against experimental data being generated by our Australian and American partners.
References
Melissa H. Little and Andrew P. McMahon: Mammalian Kidney Development: Principles, Progress, and Projections, Cold Spring Harb Perspect Biol, 2012