The team has been at the forefront of research on type 1 diabetes for over a decade. This form of diabetes is a major chronic disease from childhood, as well as accounting for at least 10% of adult-onset diabetes. It occurs when the body�s immune system attacks and destroys the beta cells in the pancreas that make insulin, the hormone that controls the level of glucose in the blood. The team was one of the first in the world, and is the only one in Australia, to develop screening programs to tes ....The team has been at the forefront of research on type 1 diabetes for over a decade. This form of diabetes is a major chronic disease from childhood, as well as accounting for at least 10% of adult-onset diabetes. It occurs when the body�s immune system attacks and destroys the beta cells in the pancreas that make insulin, the hormone that controls the level of glucose in the blood. The team was one of the first in the world, and is the only one in Australia, to develop screening programs to test and identify people at risk for type 1 diabetes. They showed that the underlying disease could start years before symptoms occurred and discovered genes that determine the rate at which the underlying disease progresses. They have also found evidence that the disease may be triggered by gut viruses called rotaviruses in genetically-susceptible individuals. They showed that type 1 diabetes could be prevented in a mouse model by getting the immune system to make a protective response to insulin, and then went on to apply this in at-risk humans in a controlled trial of intranasal insulin, the first of its kind. They have used genetic techniques not only to pinpoint the mechanisms responsible for killing the beta cells but also to modify the beta cells to make them resistant to attack by these mechanisms. The multidisciplinary approach of the team will be directed to further understanding the genetic and environmental factors underlying type 1 diabetes and the immune mechanisms, particularly involving special white blood cells called T cells, that kill beta cells. A molecular target of the immune attack, the parent of insulin called proinsulin, will be used, paradoxically, as a tool to regulate the immune system and avert the attack. This will be achieved by giving proinsulin via the mucosa of the naso-respiratory tract or via the bone marrow-derived stem cells, initiallyin the mouse model as a test of feasibility for human application. In parallel with these approaches to prevention, specially constructed viruses will be used to transfer several new genes into beta cells to improve their resistance to immune attack, so that they can be transplanted into people with established diabetes without the need for potentially toxic drugs that suppress the immune system overall. The integrated research of the team is helping to provide a sound, rational base for the eventual prevention and cure of type 1 diabetes.Read moreRead less
Intervening In The Natural History Of Type 1 Diabetes: An Integrated Approach
Funder
National Health and Medical Research Council
Funding Amount
$9,466,000.00
Summary
This Program brings together four of Australia’s top type 1 diabetes clinical and lab-based research teams. The program has three intersecting themes. The first theme, pathogenesis, focuses on early life and understanding why type 1 diabetes develops. The second theme, prevention, seeks to identifying new drugs to stop the disease from occurring. The third theme, treatment, aims to improve therapies to replace the cells that are destroyed during the disease process.
Improving The Neonatal Transition In Infants With A Congenital Diaphragmatic Hernia
Funder
National Health and Medical Research Council
Funding Amount
$551,644.00
Summary
Congenital diaphragmatic hernia is a common congenital abnormality and occurs when the diaphragm fails to separate the abdominal and thoracic compartments before birth. This prevents the lung from growing properly and so at birth, the lung is unable to take over the role of gas exchange without considerable assistance. As a result, these infants are at high risk of death or significant disability and this application is focused on improving care and reducing morbidity in these infants.
Improving The Prediction And Detection Of Contributors To Term Stillbirth
Funder
National Health and Medical Research Council
Funding Amount
$570,358.00
Summary
Stillbirths are a global human tragedy, with 1 in 130 of all pregnancies in Australia ending in stillbirth. We propose to use ultrasound and blood markers to improve the detection of babies who are not growing well, a leading risk factor for stillbirth. Sleep position has also been associated with stillbirth, so we will study fetal heart rate responses during an overnight sleep study to see if breathing events overnight may be an important contributor to stillbirth in growth restricted fetuses.
Measuring Hypoxia Induced MRNA In Maternal Blood To Monitor Wellbeing Of Growth-restricted Fetuses
Funder
National Health and Medical Research Council
Funding Amount
$421,358.00
Summary
Severely growth restricted fetuses are at peril of stillbirth from low oxygenation. While ultrasound monitoring improves outcomes, babies are still lost. Better ways to monitor the health the unborn baby are needed. We have recently discovered fetuses’ starved of oxygen leak RNA into mother's blood. Thus, measuring RNA molecules in blood could be used to assess fetal health. We will examine whether measuring mRNA in maternal blood could be used to monitor wellbeing of growth-restricted fetuses.
Environmental Influences In The Establishment Of The Epigenetic Landscape In Children
Funder
National Health and Medical Research Council
Funding Amount
$695,097.00
Summary
The DNA in each of our cells does not exist alone, it is packaged into complex structures called chromosomes, through association with many different proteins. The distribution of these proteins varies along the length of a chromosome depending on the type of cell and this phenomenon is called 'epigenetics', literally meaning 'above the DNA'. Epigenetic analysis is the study of how proteins and other molecules can change the activity of a gene without changing the DNA sequence. All of our cells ....The DNA in each of our cells does not exist alone, it is packaged into complex structures called chromosomes, through association with many different proteins. The distribution of these proteins varies along the length of a chromosome depending on the type of cell and this phenomenon is called 'epigenetics', literally meaning 'above the DNA'. Epigenetic analysis is the study of how proteins and other molecules can change the activity of a gene without changing the DNA sequence. All of our cells use epigenetic changes to help control how they grow and develop. Evidence suggests a direct link between diet and environmental influences on our epigenetic profile. Recent research has traced the origins of many of the health problems of adult life back to the earliest periods of development _ to the time spent in the womb and the first few years of life. If we are born with a low birth weight, we are more likely to get sick later in life. Overwhelming evidence exists that the environment in the womb is critical for a healthy birth weight (and health in later life) and it is thought that epigenetics may be the missing link between this environment, low birth weight, and therefore health in later life. In addition, mounting evidence supports a general link between epigenetic de-regulation and predisposition to disease. However, the timing and the overall contribution of environmental- genetic influences to the establishment of faulty epigenetic markings remain largely unknown. Twins are the best model to study this link as they share similar (but not identical environments) and some share identical genetic makeup. Using twins, Dr Jeffrey Craig and his team will investigate the factors in the prenatal environment that modify specific cells, leading to low birth weight and increase disease risk later in life. They predict that this occurs via specific changes in gene activity caused by epigenetic disruption.Read moreRead less
Defining Genetic And Epigenetic Variation During Early Development
Funder
National Health and Medical Research Council
Funding Amount
$996,075.00
Summary
We all began life with a set of genes inherited from our parents. However, it's now known that from the time we were in the womb onwards that genes can be turned off and on by the environment or even completely lost or gained. Even what your mother ate or how she behaved while she was pregnant could have influenced your future health. Because people are so different, we are studying the subtle differences between twins to tease out the factors that may influence our genes and our health.
Birth Weight, Adult Weight And Podocyte Depletion.
Funder
National Health and Medical Research Council
Funding Amount
$796,252.00
Summary
A major role of our kidneys is to filter our blood. A key cell type in our kidney filters is an octopus-shaped cell known as the podocyte. If we are not born with enough podocytes, or if the filters grow too large after birth due for example to excessive weight gain, the podocytes cannot adequately filter the blood, and this can lead to kidney disease. We will measure podocyte endowment at birth, and assess the effects of weight gain and loss after birth on podocyte features and kidney health.
Novel Therpeutic Approaches For Alzheimers Disease
Funder
National Health and Medical Research Council
Funding Amount
$604,734.00
Summary
There are currently no effective treatments for Alzheimer's disease. In this application we will develop a novel class of compound to assess their potential as AD therapeutics. These compounds will be tested in vitro and in vivo models of Alzheimer's disease. The successful conclusion of the work described here would provide new leads suitable for further development as therapeutics for Alzheimer's disease.
Defining The Epigenetic Origins Of Maternally Inherited Disease.
Funder
National Health and Medical Research Council
Funding Amount
$731,162.00
Summary
Epigenetic (non genetic) changes to the DNA in sperm and eggs can alter outcomes in children. Despite the potential for drugs and diet to mediate some of these inherited effects, the processes involved are very poorly understood. By determining the mechanisms that regulate epigenetic inheritance, this project will improve our understanding of how epigenetic mechanisms acting in the parent, can mediate inherited disease and life-long health outcomes in our children.