Mechanisms Of Glucocorticoid Resistance In Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$547,970.00
Summary
Glucocorticoids are extremely active drugs used in the treatment of childhood acute lymphoblastic leukaemia (ALL), yet a proportion of patients respond poorly to therapy and exhibit resistance at relapse. Clinically relevant mechanisms of glucocorticoid resistance are poorly understood, principally due to lack of appropriate experimental models. This project will reveal novel mechanisms of drug resistance in childhood leukaemia and lead to novel therapeutic strategies to improve outcome.
A Multi-setting Intervention To Reduce Sedentary Behaviour, Promote Physical Activity And Improve Childrens Health
Funder
National Health and Medical Research Council
Funding Amount
$860,343.00
Summary
Sedentary behaviours and physical inactivity play a major role in the rising prevalence of obesity among children in Australia. This intervention study will take place in the school and family settings which play a critical role in shaping children's health behaviours. The objective is to determine whether a 2-year behavioural intervention reduces sedentary behaviour and promotes physical activity and results in improved health among 8-9 year old children.
AusDiab 3: Emerging Risk Factors For And Long-term Incidence Of Cardio-metabolic Diseases
Funder
National Health and Medical Research Council
Funding Amount
$2,616,397.00
Summary
This study will track 11,000 Australian adults over 12 years to determine how many develop diabetes, obesity, kidney and heart disease. The study will develop ways to best predict those who are going to develop these conditions before they have arisen, and will explore a range of novel risk factors to better understand these conditions.
Roles Of Impaired Apoptosis And Differentiation In Tumourigenesis And Therapy
Funder
National Health and Medical Research Council
Funding Amount
$21,656,910.00
Summary
The ten scientific laboratories in this program have joined forces to investigate two ways in which tumours develop. Both are of particular interest, because they suggest new ways in which cancer might be overcome. Most of our tissues are continually renewed throughout life by production of new cells. Therefore many of the old cells in each tissue must die off to maintain the proper cell numbers. To eliminate cells that are no longer needed or have become damaged, the body has developed a remark ....The ten scientific laboratories in this program have joined forces to investigate two ways in which tumours develop. Both are of particular interest, because they suggest new ways in which cancer might be overcome. Most of our tissues are continually renewed throughout life by production of new cells. Therefore many of the old cells in each tissue must die off to maintain the proper cell numbers. To eliminate cells that are no longer needed or have become damaged, the body has developed a remarkable cell suicide process termed apoptosis. Unfortunately, however, occasionally a random accident to the genes in one of our cells prevents the machinery for apoptosis from being turned on. In that case, the cell will not die when it should and, by continually dividing, it may eventually give rise to a cancer. Since most cancer cells still retain most of the machinery for apoptosis, however, a drug that could switch on this natural cell death machinery would provide a promising new approach to cancer therapy. Identifying and developing such drugs is one major long-term goal of this program. The other focus of our program concerns stem cells. These are rare cells with the remarkable ability to generate an entire tissue. For example, one of our laboratories has identified stem cells that can generate all the cells in the breast. The almost unlimited regenerative capacity of stem cells has a built-in danger. If a stem cell acquires the ability to proliferate excessively, it can go on to form a tumour. Indeed, many cancer researchers now suspect that rare stem cells within a tumour cause its inexorable growth. If tumour growth is maintained by stem cells, it will be essential to develop new forms of therapy that target these rare cancer stem cells rather than merely the bulk of the tumour cells. This is another key long-term goal of our program.Read moreRead less
Epigenetic Programming Of Immune Development In Utero: Role Of The Maternal Environment In The Allergy Epidemic
Funder
National Health and Medical Research Council
Funding Amount
$764,463.00
Summary
This study will provide new insights into the development of allergic disease. Specifically, we will explore the hypothesis that allergic disease and other disorders or immune dysregulation occur as a result of gene-environmental interactions in early life, and that these events begin in pregnancy when the developing fetus is still developing and most susceptible to these effects.
How Does NF-kB2 Regulate Thymic Selection To Prevent Organ-specific Autoimmune Disease?
Funder
National Health and Medical Research Council
Funding Amount
$787,600.00
Summary
Autoimmune diseases like type 1 diabetes and thyroiditis arise from defects that cause the immune system to confuse self and non-self. Normally, this distinction is programmed in the thymus. We recently identified the gene that causes a form of autoimmune disease. We also made an important discovery about how the thymus gland regulates self-non-self discrimination. We will build on these two discoveries to gain a precise understanding of how the immune system normally avoids autoimmune disease.
Health And Fertility Of Young Men Conceived Using Intra-cytoplasmic Sperm Injection
Funder
National Health and Medical Research Council
Funding Amount
$362,570.00
Summary
The injection of a single sperm into the egg (ICSI) has been the main IVF treatment for men with poor sperm quality since 1993 but is now often used for other types of infertility. Concern has been raised about the health of the children. We will approach >800 parents and their adult sons conceived using ICSI and will assess his general health and development, and fertility. This work will improve patient counselling and practice guidelines, and direct research into the safety of ICSI.
Epidemics, mortality and longevity in Tasmania, 1838-1930. This project will investigate areas of contemporary importance that can only be explored using historic-demographic data. National benefits include (1) gaining a better understanding of how epidemics spread through families and communities, and possible mortality and case-fatality rates, to assist in preparation for future epidemics; (2) improved accuracy in projecting older-age mortality and population ageing in Australia and other coun ....Epidemics, mortality and longevity in Tasmania, 1838-1930. This project will investigate areas of contemporary importance that can only be explored using historic-demographic data. National benefits include (1) gaining a better understanding of how epidemics spread through families and communities, and possible mortality and case-fatality rates, to assist in preparation for future epidemics; (2) improved accuracy in projecting older-age mortality and population ageing in Australia and other countries; and (3) more precise estimates of women's capacity to naturally conceive and carry to term by characteristics such as her age, her partner's age, and her number of previous births. The project will also result in augmentation of a unique publicly available dataset.Read moreRead less
Chromosomes are structures that carry genes in all our cells. Every human cell has 46 chromosomes. In the nucleus of eukaryotic cells, DNA is highly folded and compacted with specific proteins into a dynamic polymer called chromatin. Gene expression, chromosome division, DNA replication, and repair all act, not on DNA alone, but on this chromatin template. The discovery that enzymes can (re)organise chromatin into accessible and inaccessible configurations revealed mechanisms that considerably e ....Chromosomes are structures that carry genes in all our cells. Every human cell has 46 chromosomes. In the nucleus of eukaryotic cells, DNA is highly folded and compacted with specific proteins into a dynamic polymer called chromatin. Gene expression, chromosome division, DNA replication, and repair all act, not on DNA alone, but on this chromatin template. The discovery that enzymes can (re)organise chromatin into accessible and inaccessible configurations revealed mechanisms that considerably extend the information potential of the genetic code. In addition, it is now established that chromatin structural features can influence gene expression. In vitro studies support a model in which chromatin functions as a barrier for the access to DNA. Therefore this organization has to be tighly regulated and dynamic to allow the protein-DNA interactions critical for nuclear functions. Importantly genome organisation provides in addition to genetic information another layer of information, so called epigenetic, which by definition means that it is stably inherited throughout cellular divisions, yet it is not encoded genetically. Thus each cell type will display a specific epigenome. We have recently constructed small human minichromosomes, which are much easier to study than the much larger normal chromosomes. The present project proposes to define the epigenetic feature across an entire human chromosome using our minichhromosomes as working models. The outcome will be a significant gain in our knowledge on the processes underlying epigenetic regulation, the organisation of specialised chromatin domain, and behaviour of the chromosomes.Read moreRead less
Reducing Prolonged Workplace Sitting Time In Office Workers: A Cluster-randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$524,613.00
Summary
Groundbreaking Australian research shows that sitting for too long, which is routine for most office workers, contributes to overweight and to a greater risk of developing diabetes and heart disease. In over 300 desk-bound office workers, this world-first study will assess the effectiveness of an innovative workplace program aimed at reducing and breaking up sitting time. It will identify practical ways for Australian office workers to minimise unhealthy effects of sitting too much at work.