The Role Of The Mammalian Grainyhead-like Gene Family In Neural Tube Closure
Funder
National Health and Medical Research Council
Funding Amount
$569,541.00
Summary
Failure of the skin to close over the brain and spinal cord during human development results in the devastating congenital birth defects anencephaly and spina bifida, known collectively as the neural tube defects. These are the second most common congenital birth defects affecting 1:1000 pregnancies. Anencephaly is not compatible with life and affected babies die at birth. In contrast children with spina bifida survive, but suffer from limb paralysis, bowel and bladder dysfunction, learning diff ....Failure of the skin to close over the brain and spinal cord during human development results in the devastating congenital birth defects anencephaly and spina bifida, known collectively as the neural tube defects. These are the second most common congenital birth defects affecting 1:1000 pregnancies. Anencephaly is not compatible with life and affected babies die at birth. In contrast children with spina bifida survive, but suffer from limb paralysis, bowel and bladder dysfunction, learning difficulties and psycho-social disturbances. Our laboratories have identified a family of genes essential for the colsure of the neural tube in mammals. The aim of this proposal is to understand the mechanisms of action with a view to developing new therapeutics that mey be used preventatively in these conditions. We also hope that these studies may facilitate the development of a genetic test to screen couples at risk.Read moreRead less
Biological, Functional And Radiographic Evaluation Of Autologous Chondrocyte Implantation
Funder
National Health and Medical Research Council
Funding Amount
$307,400.00
Summary
We will test the hypothesis that autologous chondrocyte implantation (ACI) and extensor realignment produces superior clinical, biological and radiographic results when compared with conventional treatment of realignment and debridement. We will specifically address the following aims: 1. Quantify the clinical outcome of ACI compared to the traditionally used treatment of debridement through the use of functional evaluation in a blinded randomised controlled clinical trial; 2. Evaluate the radio ....We will test the hypothesis that autologous chondrocyte implantation (ACI) and extensor realignment produces superior clinical, biological and radiographic results when compared with conventional treatment of realignment and debridement. We will specifically address the following aims: 1. Quantify the clinical outcome of ACI compared to the traditionally used treatment of debridement through the use of functional evaluation in a blinded randomised controlled clinical trial; 2. Evaluate the radiographic changes in the patellofemoral joint that occur as a result of ACI, using high resolution magnetic resonance imaging (MRI) to quantify the regeneration of hyaline articular cartilage; 3. Using the new technique of confocal arthroscopy, we will compare the histologic appearances of the ACI graft and its interface with adjacent articular cartilage; 4. Evaluate patient, surgical and explant chondrocyte characteristics in relation to functional, radiographic and biological outcomes. With respect to the matrix-induced autologous chondrocyte implantation (MACI) technique, we wish to clarify the clinical practice as a definitive treatment for articular cartilage defects. This will be the first randomised, controlled clinical trial of the MACI technique compared to that used by other groups. A positive clinical outcome from this trial will help promote the three cornerstones of this procedure – successful cell culture, efficient surgical procedures, and complimentary postoperative rehabilitation. Furthermore, this research will: a) Enhance the expansion of the MACI technique; b) Encourage development of endoscopic techniques of implantation using a combination of – • Preoperative defect registration with MRI • pre-cut custom patches, implanted with • Computer-assisted navigation techniques: c) Increase the potential to cater for a larger number of patients requiring articular cartilage repair; d) Confirm the long-term durability of regenerated cartilage in the 4th year and beyond; e) Add further commercial value by demonstrating MACI may prevent the onset of osteoarthritis.Read moreRead less
Identification And Characterisation Of Genes Required For Cardiac Morphogenesis
Funder
National Health and Medical Research Council
Funding Amount
$434,706.00
Summary
The heart is the first organ to become functional as an embryo forms, reflecting its critical role in sustaining life. Mistakes that occur as the heart develops have devastating consequences for an individualÍs survival and health. We have identified two zebrafish mutants with heart defects and, using sophisticated imaging and genetic studies, will investigate these defects and identify the genes responsible. This research will improve our understanding of correct and diseased heart formation.
Identifying The Critical Pathways Which Regulate Vertebrate Craniofacial Development
Funder
National Health and Medical Research Council
Funding Amount
$552,131.00
Summary
Understanding the genes which underlie human birth defects is of immense clinical importance. Our laboratory is a world-leader investigating a gene responsible for facial skeleton development, Grhl2. With our wide range of models, we will discover how Grhl2 works to ensure the face and skull develop properly during birth.
Investigating The Genetic Cause Of Genital Abnormalities In Males
Funder
National Health and Medical Research Council
Funding Amount
$299,564.00
Summary
This project investigates the genetic cause of a relatively common defect in male genitalia, hypospadias, in which the penis opening is aberrantly located. Hypospadias affects 1 in ~250 males, usually requires surgery and can cause problems with intercourse and urination. Using new technologies to study patient DNA, we will identify mutations causing hypospadias and new genes involved in development of the male genitalia. This will lead to improved clinical diagnosis and management of patients.
An Exploration Of Cerebral Palsy Aetiology: Assisted Reproductive Technology And Congenital Anomalies
Funder
National Health and Medical Research Council
Funding Amount
$89,420.00
Summary
Cerebral palsy (CP) is the most common physical disability of childhood, describing a group of permanent disorders of movement caused by damage to the developing brain. The causes of CP are poorly understood for most people. This study will explore and quantify the impact of two known risk factors on CP: assisted reproductive technology and congenital anomalies. When these causes of CP are better understood, possibilities for prevention of this disability can be sought.
The Role Of The MYST Family Transcriptional Co-activator, Mof, In Embryonic Development
Funder
National Health and Medical Research Council
Funding Amount
$319,446.00
Summary
A major task in biology is to understand how the human genome directs the development of a single cell to form an entire individual. Clearly, a large part of this task is to understand how the expression of genes is regulated during embryonic development. Gene expression requires co-activator complexes. Co-activator complexes typically contain proteins which regulate the structure of chromatin (a complex of DNA and histones). However, the physiological function of most co-activators is entirely ....A major task in biology is to understand how the human genome directs the development of a single cell to form an entire individual. Clearly, a large part of this task is to understand how the expression of genes is regulated during embryonic development. Gene expression requires co-activator complexes. Co-activator complexes typically contain proteins which regulate the structure of chromatin (a complex of DNA and histones). However, the physiological function of most co-activators is entirely unclear. The aim of this project is to study the function of Mof during embryonic development. Mof is a co-activator that directly regulates chromatin structure by modifying histones. Mof is a member of the MYST family of co activators, which includes Moz and Qkf. We have recently shown that Moz and Qkf are essential for the haematopoietic stem cell population and the neural stem cell population, respectively. The purpose of this project is to produce a detailed analysis of the function of Mof in vivo and determine it's importance in regulating gene expression. All biological processes relay on accurate regulation of gene transcription and all diseases, whether they involve pathogens or cell intrinsic pathological changes, such as cancer, lead to changes in gene expression. Regulation of chromatin structure has been identified as a major mechanism of transcriptional regulation in health and disease. However, our understanding of the precise molecular mechanisms regulating chromatin structure in vivo are very limited. This work will fully investigate the role of an important co-activator in vivo including a mechanistic analysis. This will increase understanding of how gene expression is regulated and, ultimately, this knowledge will find wide application in the development of new treatment paradigms.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.