Understanding kidney development through multi-scale imaging and modelling – Alexander Combes

Despite progressive discovery of genetic pathways that impact on development, the coordinated cell movement, growth, and differentiation involved in establishing organ systems required for animal life is poorly understood. Understanding the regulation of organ size and architecture has been particularly intractable due to technical issues arising from tissue size and complexity. We have taken a multi-scale imaging approach combining optical projection tomography and confocal microscopy to deliver tissue- and cellular-level information. This multi-scale imaging approach is yielding quantitative insights into progenitor heterogeneity, how renal capacity is built, and has facilitated novel insight through mathematical modeling in collaboration with the Hamilton (UQ) and Byrne (Oxford) laboratories. Our team has recently developed methods to enable timelapse imaging within cultures of the developing mouse kidney that reveal novel cell behaviours which challenge the dogma about nephron progenitor organization and regulation. Recent developments in directed differentiation of human kidney organoids and high throughput single cell RNA-Seq have renewed interest in development and reinforced the importance of imaging cell types and proteins in their native 3D environment.


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