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Only recently has it emerged that our cells have a built-in backup mechanism that instructs cells to die in extreme cases, such as when viruses have hijacked a cell. A misfiring backup mechanism is thought to underlie a number of human diseases, including inflammatory disease. Our investigation will establish a starting point for the development of novel anti-inflammatory drugs.
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
Mental Health Across Generations: Pre-and Post Conception Predicators Of Early Life Risks
Funder
National Health and Medical Research Council
Funding Amount
$666,231.00
Summary
In 2003, mental illnesses were among the ten leading causes of disease burden in Australia, accounting for 13% of the total burden of disease, according to the Australian Institute of Health and Welfare. Mental health problems and mental illness are among the greatest causes of disability, diminished quality of life, and reduced productivity. People affected by mental health problems often have high levels of morbidity and mortality, experiencing poorer general health and higher rates of death f ....In 2003, mental illnesses were among the ten leading causes of disease burden in Australia, accounting for 13% of the total burden of disease, according to the Australian Institute of Health and Welfare. Mental health problems and mental illness are among the greatest causes of disability, diminished quality of life, and reduced productivity. People affected by mental health problems often have high levels of morbidity and mortality, experiencing poorer general health and higher rates of death from a range of causes, including suicide. These conditions are significant in terms of prevalence and disease burden, and have far-reaching impacts for families, carers and others in the community. Mental health problems commonly cluster in families. However, few studies have previously been able to investigate the range of ways in which mental disorders may pass from one generation to another. Further, evidence suggests that influences that arise prior to conception may have major effects on early life risks such as development in utero, birth outcomes and early maternal infant bonding. Mental Health across Generations: Pre- and post-conception predictors of early life risks is a unique study that will examine antenatal maternal mental health and risk behaviours during pregnancy. The study will also examine the links between prior maternal mental health and later birth outcomes, and post natal maternal infant bonding. The risk processes to be tested will include genetic, epigenetic (changes in gene expression), physiological and psycho-social parameters.Read moreRead less
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
Apoptosis And Stem Cells In Cancer Development And Therapy
Funder
National Health and Medical Research Council
Funding Amount
$22,852,198.00
Summary
To improve cancer therapy, we are studying two cancer hallmarks: enhanced cell survival and stem cell-like behaviour. As we discovered, cell death is often blocked in cancer cells. Hence, we are attempting to develop drugs that flip the natural ‘cell death switch’. Stem cells are rare cells that generate entire tissues, as we showed for the breast. Certain cancers may be driven by ‘rogue’ stem cells. If so, eradication of these rare cells within the bulk tumour may require novel therapies.
Microenvironments which support extramedullary hematopoiesis. Tissue regeneration is a breakthrough technology absolutely dependent on knowledge of the stem cells and stromal cells which support differentiation and tissue development. This project investigates the stromal cell types in spleen which can regenerate blood-forming cells in an ectopic tissue site or artificial matrix.
Epigenetic reprogramming of development by nutritional factors in honeybee. The project aims to study the mechanism by which a specialised nutrition can change or even reverse the process of adult cell fate. The project will use a previously unexplored method of nutritional reprogramming of imaginal discs in honeybees by royal jelly and identify novel components of both the genetic and epigenetic systems that are most potent as reprogramming factors. The project seeks to improve our understandin ....Epigenetic reprogramming of development by nutritional factors in honeybee. The project aims to study the mechanism by which a specialised nutrition can change or even reverse the process of adult cell fate. The project will use a previously unexplored method of nutritional reprogramming of imaginal discs in honeybees by royal jelly and identify novel components of both the genetic and epigenetic systems that are most potent as reprogramming factors. The project seeks to improve our understanding of how epigenetic remodelling of the information content of the genome contributes to conversion of cell fate in vivo and in vitro. More broadly, the project could potentially establish the honeybee imaginal discs as a model for understanding pluripotency and environmentally controlled developmental plasticity.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE210100011
Funder
Australian Research Council
Funding Amount
$900,000.00
Summary
Integrated Multimodal System for Multiplexed Imaging of Signal Transduction. This project will introduce a unique microscopy platform and associated technologies into the Australian research environment that will enable researchers to redefine our understanding of molecular signal transduction. The instrumentation will enable the multidimensional imaging of live cells with unprecendented speed and sensitivity. The featured imaging modalities will enable the integration of distinct biological, ....Integrated Multimodal System for Multiplexed Imaging of Signal Transduction. This project will introduce a unique microscopy platform and associated technologies into the Australian research environment that will enable researchers to redefine our understanding of molecular signal transduction. The instrumentation will enable the multidimensional imaging of live cells with unprecendented speed and sensitivity. The featured imaging modalities will enable the integration of distinct biological, biochemical and chemical probes with a focus on minimizing phototoxicity. Expected outcomes include new fundamental knowledge on molecular signal transduction and cell heterogeneity; development of novel probes and methodologies and the development of new and existing interdisciplinary research collaborations. Read moreRead less
Gamete-specific knockout of Fizzy-Related to examine its meiotic role in oocytes and sperm. Fizzy-Related is a gene that appears to be essential in making an ovulated egg, and it may also have an important role to play in making sperm. A mouse knockout will be generated to examine exactly how it functions; because it affects the egg number remaining in the ovary and egg quality Fizzy-Related may be eventually an important therapeutic target.
Multi-object Estimation for Live-Cell Microscopy. The objective of this project is to develop new tools for the inference of biological information from live-cell data to facilitate analysis of experiments and speed up discovery in cell biology. The new tools would provide reliable, consistent inference requiring no manual intervention and able to process large volumes of data in a timely manner. This would equip biologists with a vehicle that could move them closer to the goal of understanding ....Multi-object Estimation for Live-Cell Microscopy. The objective of this project is to develop new tools for the inference of biological information from live-cell data to facilitate analysis of experiments and speed up discovery in cell biology. The new tools would provide reliable, consistent inference requiring no manual intervention and able to process large volumes of data in a timely manner. This would equip biologists with a vehicle that could move them closer to the goal of understanding the mechanism behind biological processes.Read moreRead less