Diseases of the 21st century are complex with environmental and genetic causes. At the interface of these is Epigenetics - factors not specified by DNA sequence that control genes. Recent data show much of the risk associated with disease is set early in life, even during the time in the womb. The MCRI CDDE laboratory has assembled teams of researchers of diverse expertise investigating epigenetics of human development and complex disease to hopefully prevent or reverse them early in life.
Validation Of A Multiplexed Blood Based Screening Assay For The Diagnosis Of Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$556,712.00
Summary
Colorectal cancer (CRC) is the second most common cancer in Australia with poor patient outcome due to late detection of the disease. We have developed a simple blood based test that can diagnose individuals with CRC at an early stage when the chance of cure is greater than 80%.
Molecular Characterisation Of Early Precursor Lesions Of A Novel Ñserrated Pathwayî Of Colorectal Cancer Using Gene Expression And Proteomics.
Funder
National Health and Medical Research Council
Funding Amount
$318,338.00
Summary
In Australia, CRC is the second highest cause of all cancer-related deaths. If detected early, CRC has a high success rate of cure, but a percentage of precursor lesions escape detection and show aggressive clinical behaviour to progress to CRC. These are difficult to diagnosis with existing technologies. We aim to understand the biology behind sessile serrated adenoma pathways and hence enhance early detection, diagnosis and treatments strategies.
ADAM Metalloprotease Inhibition For Treatment Of Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$770,925.00
Summary
Colorectal cancer (CRC) causes over 4000 deaths/year, typically from developing drug resistance and spreading to other organs (metastasis). These processes involve tumour cells called cancer stem cells (CSCs), which rely on specific cell surface proteins for survival and function. We are developing antibodies against one of these type of proteins, to test in mouse models of CRC. These already show promise in targeting CSCs and inhibiting drug-resistance and metastasis in mice.
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
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
Radiotherapy Treatment For Prostate Cancer - A Change In Practice Based On Direct Evidence For Targeting And Toxicity Effects Using Real Outcomes Data
Funder
National Health and Medical Research Council
Funding Amount
$555,129.00
Summary
Radiotherapy for prostate cancer treatment will be more effective when we have better knowledge of what patient anatomy needs to be targeted, and what needs to be avoided. This project will combine data collected during a large Australasian prostate cancer radiotherapy trial, ‘RADAR’, with data collected using new patient imaging methods to determine how patient anatomy impacts on the effectiveness of their treatment and the side-effects they experience.
Applying search theory for eradicating invasive species. Invasive species have major economic and environmental impacts in Australia and are a major cause of extinctions worldwide. Monitoring is crucial for the timely control of invasive species in sensitive environments. Early detection increases the probability of eradication and increased accuracy in detection reduces the impact of control programs on non-target species. Efficient monitoring also is crucial in determining whether eradication ....Applying search theory for eradicating invasive species. Invasive species have major economic and environmental impacts in Australia and are a major cause of extinctions worldwide. Monitoring is crucial for the timely control of invasive species in sensitive environments. Early detection increases the probability of eradication and increased accuracy in detection reduces the impact of control programs on non-target species. Efficient monitoring also is crucial in determining whether eradication has succeeded. Search Theory has been applied for over 60 years in a wide range of non-biological monitoring problems, resulting in large increases in target detection rates. Gains of a similar magnitude in invasive species detection would greatly enhance Australia's capacity to manage these threats.Read moreRead less
Improving external validity of stated choice experiments. This project aims to deliver more accurate estimates of choice behaviour by reducing biases due to choice task complexity in surveys as well as design artefacts. Extracting 'true' preferences is challenging, not only due to possible hypothetical bias, but also due to increasingly complex choice tasks and the existence of design artefacts. This project will investigate the latter two in the context of marketing, transport, health, and envi ....Improving external validity of stated choice experiments. This project aims to deliver more accurate estimates of choice behaviour by reducing biases due to choice task complexity in surveys as well as design artefacts. Extracting 'true' preferences is challenging, not only due to possible hypothetical bias, but also due to increasingly complex choice tasks and the existence of design artefacts. This project will investigate the latter two in the context of marketing, transport, health, and environmental economics, and proposes new methodologies to extract preferences that more closely reflect true behaviour in real markets.Read moreRead less
Alpha-particles linked to recombinant antibodies targeting tumour cells have potential to effectively treat tumours while minimising normal tissue side effects. We will explore a novel alpha-particle therapy approach to solid tumours, by delivering 225Ac directly into tumour cells, or into cells that support the tumour (microenvironment). This approach will hopefully result in development of a new approach to treatment of cancers that are resistant to conventional therapies.