Project Description

Dr Alexander Combes

Murdoch Children’s Research Institute (MCRI)
University of Melbourne

Understanding kidney development through multi-scale imaging and modelling

Advanced microscopy analysis and modelling

Friday 6 July 2018

Dr Alexander Combes is an emerging leader in developmental biology, known for integrating multi-scale imaging data to build a holistic picture of organogenesis. Awarded a PhD in 2009 from The University of Queensland (UQ), Dr Combes undertook postdoctoral studies in the laboratory of Prof. Melissa Little at UQ/Murdoch Children’s Research Institute (MCRI) and spent time abroad at Columbia University (New York, USA). A former DECRA fellow, Dr Combes now leads team within Prof. Melissa Little’s lab at the University of Melbourne and MCRI focused on the molecular regulation of kidney development. His work involves wholemount imaging of live and fixed tissues using a range of microscopy platforms and has benefited from collaboration with leading biomathematicians including Dr Nick Hamilton (UQ), and Prof. Helen Byrne (Oxford). His work has changed the way we think about renal progenitor populations and demonstrated that the functional capacity of the kidney can be enhanced in vivo.

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.