Interaction Between Moz And PRC1 In Defining Epigenetic States And Gene Expression Patterns
Funder
National Health and Medical Research Council
Funding Amount
$427,271.00
Summary
Regulation of gene expression is implicated in all disease processes. Aberrant gene expression is particularly associated with tumour formation. In this project we determine the relationship between an oncogene MOZ and another oncogene BMI1. Together these proteins regulate one of the most important systems controlling gene expression at the level of chromatin structure.
The Role Of The Transcriptional Co-activator, Qkf, In Adult Neural Stem Cell Self-renewal And Multi-potency.
Funder
National Health and Medical Research Council
Funding Amount
$403,709.00
Summary
In recent years there has been considerable interest in stem cells because they have the potential to provide new therapeutic approaches to disease. Indeed, haematopoietic stem cells are already used in treatments for leukaemia. Many organs in adult humans contain stem cells, including the brain. In order to develop safe, and effective, stem cell-based treatments for human diseases it is necessary to determine how proliferation and differentiation are regulated in adult stem cells.
Control Of Blood Vessel Development By SOX Transcription Factors
Funder
National Health and Medical Research Council
Funding Amount
$495,750.00
Summary
Cardiovascular disease is Australia s greatest health problem, with an estimated 3 million Australians suffering a spectrum of conditions from hypertension through to heart failure. Improper development of blood vessels in the embryo can compromise survival of the embryo, and predispose patients to vascular disease after birth. The growth of new blood vessels (angiogenesis) is also an important factor in the ability of solid tumours to grow during the progression of cancer. It is therefore of fu ....Cardiovascular disease is Australia s greatest health problem, with an estimated 3 million Australians suffering a spectrum of conditions from hypertension through to heart failure. Improper development of blood vessels in the embryo can compromise survival of the embryo, and predispose patients to vascular disease after birth. The growth of new blood vessels (angiogenesis) is also an important factor in the ability of solid tumours to grow during the progression of cancer. It is therefore of fundamental importance in the health sciences to gain an understanding of how blood vessels form and regenerate. We discovered a gene, Sox18, that appears to regulate blood vessel development by controlling the formation and-or properties of endothelial cells, which line the blood vessels and make them impermeable. Our research so far indicates that MICE WITH DEFECTS IN SOX18 DIE FROM VASCULAR DEFECTS, underlining the importance of this gene. THIS PROJECT IS CONCERNED WITH FINDING OUT HOW SOX18 WORKS - exactly what goes wrong in mice lacking this gene, whether Sox18 can influence endothelial cell behaviour in cell culture, how Sox18 comes to be active in endothelial cells, what genes are switched on by Sox18, and what genes Sox18 co-operates with in its role in endothelial cells. The answers to these questions will not only provide fundamental basic information about how blood vessels development is controlled, but also sow the seeds for possible future therapies in which blood vessel development could be stimulated (eg in wound healing) or suppressed (eg in tumour progression) by drug treatments.Read moreRead less
Redefining Proprioceptive Circuitry At A Molecular Level
Funder
National Health and Medical Research Council
Funding Amount
$564,482.00
Summary
Neurons form an extensive series of connections to relay information across the entire body. It is essential to understand how neurons know to find their way, and form the right connections, in a developing animal. This project will investigate the genes which control formation of neural circuits that are essential for correct movement.
Elucidating The Role Of MiR-196 In Formation Of The Axial Skeleton
Funder
National Health and Medical Research Council
Funding Amount
$520,087.00
Summary
Exquisite regulation of gene expression is a fundamental principle underlying growth and development of an embryo as well as homeostasis in the adult. Following the identification of hundreds of microRNAs within the genome which act to modulate gene expression, the challenge and the goal of these studies, is to identify individual microRNAs which contribute significantly to bone formation in the developing embryo.
One of the most critical steps in embryonic development is the assembly of the different tissue components into a three-dimensional structure in order to build a major body part of the foetus. In the development of the head, this form-shaping process undertaken by different cell populations is coordinated by genetic activity that is triggered by signals received by cells. The objective of our research is to understand how one of the many signalling mechanisms, WNT signalling, works in making the ....One of the most critical steps in embryonic development is the assembly of the different tissue components into a three-dimensional structure in order to build a major body part of the foetus. In the development of the head, this form-shaping process undertaken by different cell populations is coordinated by genetic activity that is triggered by signals received by cells. The objective of our research is to understand how one of the many signalling mechanisms, WNT signalling, works in making the head and face of the embryo. We will study the development of embryos of mice in which mutations have been introduced experimentally in genes that code for factors of the WNT signalling pathway. Understanding the complexity of tissue interactions and the interplay of molecular mechanisms of head formation in the embryo is a major challenge. However, knowledge of the processes in animal models will contribute to a better delineation of the role of signalling in normal head development. It will also help to direct the focus of future clinical investigations to the most relevant genetic determinants of birth defects of the head and face, which is present in about 8 per 10,000 births in Australia.Read moreRead less
The Role Of The MYST Family Lysine Acetyltransferase, Hbo1, In Development And In The Adult
Funder
National Health and Medical Research Council
Funding Amount
$403,368.00
Summary
This project will produce a detailed analysis of the function of Hbo1, a transcription factor, and determine its importance in regulating gene expression. All biological processes rely on accurate regulation of gene transcription and all diseases lead to changes in gene expression. This work will increase understanding of how gene expression is regulated and, ultimately, this knowledge will find wide application in the development of new treatment paradigms.
Genetics Of Intersex: Antagonism Between Male And Female Pathways During Gonadal Development
Funder
National Health and Medical Research Council
Funding Amount
$567,760.00
Summary
Disorders of sex Development (DSD) are congenital conditions in which development of chromosomal, gonadal or anatomical sex is atypical. Estimates suggest that between 1-100 and 1-300 live birth have DSD; however, the underlying genetic defect is unknown in 80% of cases. Generally, the fate of the gonad, testis or ovary, is determined by the balanced action of male (SRY) and female (Wnt- b-catenin) genes. How do these genes oppose each other? Is this antagonism deregulated in DSD patients?
The Role Of The Suppressors Of Cytokine Signalling 6 And 7 In Cerebral Cortex Development
Funder
National Health and Medical Research Council
Funding Amount
$377,189.00
Summary
Defects in neuronal cell migration during embryonic development lead to mental retardation and epilepsy. Although neuronal migration is essential for the development of normal intelligence, we know relatively little about the molecular mechanisms that regulate this process. We have identified two proteins, Socs6 and Socs7, which are essential for neuronal migration and normal cerebral cortex development. We propose to fully investigate the function of Socs6 and Socs7 during cortex development.