New integrated models in the study of cardiac development and disease

Dr Gonzalo del Monte Nieto, Monash University

2018 Future Leader Fellowship

Years funded: 2019-2022

Cardiovascular disease is the major killer in Australia with congenital heart disease (CHD) affecting 1 in 100 live born babies. Although paediatric surgeries have improved the outcome for CHD patients, there is uncertainty regarding the long-term problems that these patients may suffer. Only the understanding of disease causation will allow us to optimise genetic screening and to improve therapies to ameliorate disease sequelae.

The heart is a complex biological pump in which cell inter-communication, and forces originating from the heartbeat control its development and function. However, the building plan controlling its formation is mostly unknown, limiting the application of current knowledge to cardiac disease and regeneration.

During the last few years, Dr Gonzalo del Monte Nieto has developed a revolutionary model for cardiac chamber formation focusing on trabeculae - a sponge-like specialised cardiac muscle critical for normal cardiac function both in embryos and the adult. In the model, Dr del Monte Nieto identified the main mechanisms that execute the trabecular building plan. Furthermore, I have applied for the first time notions described in the formation of blood vessels to the formation of the heart generating new approaches to understand cardiac development. The knowledge obtained will also improve our understanding of CHD causation and cardiac regeneration allowing us to design more effective treatments for patients and better methodologies to generate tissues for transplantation.

This proposal aims to integrate into my model the importance of how muscle cells divide in the cardiac chambers and how heart formation is modulated by the forces originating from the heartbeat. I also aim to apply this knowledge to better understand cardiac valves and coronary vessels formation, and the diseases associated with them. Furthermore, I aim to improve the understanding of the trabecular development defects leading to Non-Compaction Cardiomyopathy, the third most commonly diagnosed cardiomyopathy.