Division Head: Professor Richard Harvey
After conception, the fertilized egg begins the complex process of development through embryonic and foetal stages, a process controlled by the selective switching of genes. The aims of the Developmental Biology Program are to understand how different genes function and work together to affect the overall development of an animal and its organs. When we understand these genetic pathways, we will be one step closer towards understanding how congenital birth defects occur and how we may predict and manage them. The Developmental Biology Program consists of three groups, all of which have independent aims.
Professor Richard Harvey's Laboratory
The Developmental Biology Program was established in 1998 when Professor Harvey joined the Institute. Professor Harvey's group studies the genetic regulation of heart development. The heart is a relatively simple structure that acts in embryonic and adult life as a pump. However, the generation of its form during embryonic development is complex, and even the slightest deviations from normal are catastrophic for the individual. Proper heart development involves interactive regulatory gene networks and dialogue between different cell types.
The laboratory uses the mouse as a model genetic system in which to study these issues. Using the mouse, they can look at the consequences of gene loss on heart form and molecular pathways, information that can help them understand how muscle cells are specified, how heart chambers come in to being, and how function relates to form.
Heart development goes wrong in an alarming number of children (about 1 in 100), and the laboratory also studies the links between the developmental genes under study and congenital heart defects.
Adult Cardiac Stem Cell Research
Headed by Professors Harvey, Feneley and A/Prof Fatkin this laboratory concentrates on identifying stem cell populations in the adult heart and defining cell surface markers on these cells that will enable accurate purification. In addition the lab is developing biological tests to assess how stem cells are contributing to tissue regeneration. To test tissue regeneration the lab is utilising two mouse models of heart disease, myocardial infarction and ischaemia/reperfusion. These models should help track the behaviour of stem cells in healthy life and heart disease, and to find ways to augment their regenerative potential. The Adult Cardiac Stem Cell Research Laboratory is partially funded by the Australian Stem Cell Centre.
A/Professor Sally Dunwoodie's Laboratory
Another laboratory in the Developmental Biology Program is headed by A/Prof Sally Dunwoodie. She joined the Institute in 2000, and in 2003 was the inaugural recipient of one of two Senior Research Fellowships from the Pharmacia Foundation Australia. Dr Dunwoodie's research illustrates that the analysis of gene function in animals can greatly assist an understanding of the causes of inherited birth defects in humans.
A particularly good example of this is the gene Delta3 which was discovered by A/Prof Dunwoodie in 1996. Using "gene knockout" technology in mice, she created a line of mice in which this gene is mutated so that it no longer functions properly. In mice carrying the mutated gene, the vertebrae and ribs form in a very disorganised manner, resulting in a shortened spine and tail. The appearance of these mutant mice is very similar to that of people with an inherited birth defect called spondylocostal dysostosis (SCD). This observation has led to the discovery that some cases of SCD are indeed caused by mutation of the human version of the Delta3 gene. Thus studying this gene in mice has contributed to the understanding of the genetic cause of a human birth defect, providing the opportunity to develop a diagnostic test for this condition.
In addition to the Delta3 gene, the laboratory is currently investigating two other genes (called Cited1 and Cited2) which may also be involved in causing human birth defects. Both of these genes are required for the normal development of the placenta (afterbirth), while Cited2 is also required for the formation of the neural tube and the heart. Again "gene knockout" technology has been used to create mouse lines in which these genes have been rendered non-functional. Much of the current focus of the group is on the Cited2 mouse line.
In particular we are addressing two important issues. Firstly, since both the heart and placenta develop and become functional at about the same time, and are both essential to provide oxygen to the developing embryo, we are interested in seeing whether a poorly formed placenta can stop the heart from forming correctly, and vice versa. Secondly, we are looking at how oxygen levels within the developing embryo can affect how the heart and placenta form. We are also comparing the defects seen in the mutant mouse lines with previously described human birth defects in the hope of identifying cases of human disease that are caused by mutation of the Cited1 or Cited2 genes.
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