Blog / 25 February 2019

Here at the Australian Regenerative Medicine Institute, we’re investigating the potential of regenerative medicine to treat and, hopefully, one day prevent, congenital heart disease.

‘Congenital heart diseases’ (CHDs) are the most common serious birth defect in Australia and internationally, affecting 1 in 100 live-born babies. With this troubling statistic, chances are many of us will know of someone born with CHD. This disease is the result of problems while the embryo is forming, a time when cells in the embryo are moving around to form complex organs, including the heart. Issues that occur during this process result in defects in the heart's structure leading to disruptions to normal blood flow, with complications ranging in severity from mild to life-threatening. This is CHD.

‘Congenital heart diseases’ (CHDs) are the most common serious birth defect in Australia and internationally, affecting 1 in 100 live-born babies.

Sadly, each week, approximately four infants die from CHD. Fortunately, most babies do survive. However, they often require lifelong - and expensive - cardiovascular care. Advances in medical technologies have increased the number of CHD patients who do reach adulthood. Yet, despite this, the actual causes of 80% of CHD cases remain unknown. Improving our knowledge of the causes of CHD is crucial as we will then be able to provide CHD patients answers and help them better understand the risk of CHD occurring in their own children.

Without detailed knowledge about what guides normal heart formation in an embryo, we cannot understand what has gone wrong when babies are born with structural heart defects. Normal heart development is dependent on intact instructions in the form of a healthy genome. These genetic instructions precisely control the behavior of embryonic cells during heart formation. For example, a healthy genome instructs normal development of the blood vessels attached to the heart. However, it is generally known that errors in the genome can result in abnormal cardiovascular development. This is where our researchers come in.

ARMI and Congenital Heart Disease Research

At ARMI, the Ramialison group is a multidisciplinary team of computational and molecular biologists who specialise in and focus on understanding the genetic basis of CHDs and finding these errors. Led by Dr Mirana Ramialison, this group combines biological data and computational expertise in bioinformatics, which is considered the future in investigating these complex, poorly understood diseases.

“Specifically, our group is looking at the role of non-coding DNA in congenital heart disease. Non-coding DNA is a term used to describe the parts of our DNA that don’t contain the genetic blueprint for a protein. For a long time, it was thought that these regions were just ‘junk DNA’ and had no function. We now recognise that non-coding DNA actually plays a major role in regulating levels of gene expression and as such, may be the key to improving our understanding of CHD causation,” explains Mirana.

Identifying disease causing changes in the non-coding DNA is difficult and requires advanced and custom-built bioinformatics and computer modelling expertise. By integrating biological data, the Ramialison group is better equipped to find these genetic needles in a haystack which may be causing CHD. “This approach is definitely at the forefront of biomedical research. Using computer modelling, we can make sense of the large quantities of genetic data we collect. It can help us really see the big picture while pinpointing the smallest of changes,” commented Mirana.

We can help people with CHD understand the genetic risks to others in the family and one of the major implications of this work is improved genetic counselling.

A better understanding of the genetic basis of heart formation and what has gone wrong in CHD cases empowers patients. “I have spoken to many people with CHD over the years and the one thing a lot of them have told me is how much they want answers, to know why this has happened. I want to be able to give that to them. But there’s more than just that, we can help people with CHD understand the genetic risks to others in the family and one of the major implications of this work is improved genetic counselling,” said Mirana. Ultimately, the goal of this research is to help people affected by CHD.

Support ARMI’s goal to understand more about congenital heart disease, to improve genetic counselling and to develop new treatments.