Development & Stem Cells
The architecture of our adult tissues and organs is established during development before, and shortly after, birth. It is clear that an individual's development can be critically impacted by genetics, the quality of the gametes involved in conception, as well as the in uteroand postnatal environments. Thus, events before birth and in the early postnatal period can increase the chances of birth defects, childhood disease, and chronic disease in adulthood.
Understanding the basis of organ development is the key to the development of regenerative therapies. Unlocking the potential of stem cells is a high priority for regenerative medicine and for improving treatment options for a number of conditions such as diabetes, cardiovascular disease, neurological disease, autoimmune disease and cancer.
Emerging evidence is also suggesting that compromised development and adult health can be transmitted across generations. This is achieved through a range of mechanisms broadly characterized as epigenetic. As such, the mechanisms that define germ cell development/function and the importance of epigenetics broadly is a focus of this theme.
Who we are
The Development and Stem Cells program comprises 21 primary group leaders and their research teams. The program is enhanced by the involvement of a further 18 affiliated groups from other BDI Discovery Programs.
Our program has a strong legacy of research excellence. Together with the Australian Regenerative Medicine Institute (ARMI), we form the leading developmental biology and stem cell community in Australia, and one of the strongest globally. Our research interests range from the genetic and molecular regulation of embryo and fetal development, kidney biology, through to stem cell biology and patterning, reproductive biology and the anatomy of the adult body.
The goals of the Development and Stem Cells Discovery Program are to:
- Define the fundamental processes of fertilisation, the impact of environment on these processes and their importance in trans-generational health
- Understand the genetic and environmental regulation of tissue and organ development
- Define the mechanisms underlying healthy embryonic and fetal development
- Understand the adult health consequences of suboptimal fetal development and premature birth
- Understand the roles of stem cells in development and to maximise their potential in the regeneration of organs following disease
- Develop strategies for the detection, prevention and treatment of birth defects and chronic disease
- Develop new approaches to treat infertility and preserve fertility.
Our goals are being achieved through a multidisciplinary approach spanning cell and molecular biology, imaging, physiology, human genetics, engineering and the pre-clinical testing of new therapeutic strategies.
Our strengths and foci lie in the following areas:
Stem cells and regeneration
We explore the cellular and molecular mechanisms involved in cell fate decisions, differentiation and tissue regeneration and the role of stem cell dysfunction in disease development. We also research:
- Mechanisms of adult stem cell self-renewal and differentiation and how these change with disease and ageing
- New molecular targets for the manipulation of adult stem cell function to develop better stem cell therapeutics
- Tissue-specific stem cells such as those of the gut, thymus, kidney and prostate for regenerative medicine
We work to understand the developmental processes of oocytes and sperm, the origins of human infertility, and the consequences of poor gamete quality for offspring health. We explore:
- The molecular bases of human male infertility and its relevance to health broadly
- Mechanisms of maternal aging with a view towards improving the reproductive health of older women and the genetic mechanisms underlying polycystic ovary syndrome which is a major cause of female infertility
- Molecular mechanisms underlying sex determination and disorders of sex determination
- Pathways involved in the epigenetic modifications of the germ-line and early embryo/fetus as well as pathways through which in utero and early postnatal exposure, including premature birth, predispose an individual to adult disease.
- Avenues for preserving fertility, particularly in pre-pubertal boys, girls and women with cancer and identifying non-invasive predictors of oocyte quality
- Methods for diagnosing development disorders and the causes of abnormalities in sex determination
Our research aims to gain a better understanding of how the kidney develops, the genetic causes of congenital kidney defects and elucidating what the responsible genes do during development. We aim to:
- Determine the mechanisms underlying branching morphogenesis in the kidney
- Understand how different genes act to regulate organ formation and the specification of nephron number – an important determinant of adult health
- Determine how maternal behaviour affects kidney development in the unborn child
- Partner with clinical collaborators to identify novel genes involved in kidney disease and to model these in vivo
- Formulate stem cell therapies for kidney regeneration (see stem cells above)
We are focussed on the development of new approaches for the detection, prevention and treatment of adult and childhood diseases. On a broader time scale we are interested in the greater evolutionary context of human developmental processes. Our research aims to:
- Integrate information from deep human evolutionary history to understand how particular traits have evolved and the impact of adaptation to environment/diet on these processes
- Define the genetic and environmental mechanisms driving normal organ development (including of the lung, prostate, gut), and to understand how changes in these pathways lead to childhood or adult diseases