Proteomic Screening For Apoptotic Markers In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$531,696.00
Summary
The induction of apoptosis, or programmed cell death, is a key factor in the response of tumours to chemotherapeutic agents and ionising radiation; therefore biological markers that predict the clinical outcome to these therapies are needed. Over the past 2 years, our laboratory has developed techniques of protein analysis to evaluate changes in proteins during apoptosis caused by chemotherapeutic agents. Preliminary protein profiling studies of apoptosis induction in human breast cancer cell li ....The induction of apoptosis, or programmed cell death, is a key factor in the response of tumours to chemotherapeutic agents and ionising radiation; therefore biological markers that predict the clinical outcome to these therapies are needed. Over the past 2 years, our laboratory has developed techniques of protein analysis to evaluate changes in proteins during apoptosis caused by chemotherapeutic agents. Preliminary protein profiling studies of apoptosis induction in human breast cancer cell lines showed time-dependent decreases in two proteins, identified as S100A6 and ubiquitin. Both are known to be important in cell function. In the proposed project we will build on our preliminary findings to provide important new information central to the understanding of cancer cell biology and apoptosis in addition to evaluating the ability of anti-cancer treatments to induce apoptosis. Using a combination of protein analysis technologies, this project has the potential to provide reliable and novel biomarkers which will indicate the efficacy and selectivity of anti-cancer treatments in inducing tumour cell death. The knowledge gained in this project will aid clinical assessment of the response to cancer treatment(s) in patients in the form of specific screening assays, and may result in identification and development of effective new agents for cancer treatment and prevention. Furthermore, the outcomes of this project will increase our understanding of fundamental cancer cell biology and apoptosis.Read moreRead less
Development Of High-throughput Screening Assays For Detecting Early Gastric Cancer: Translating Proteomics Research Into Clinical Outcomes Using Emerging Mass Spectrometry And Photonics Technologies
Funder
National Health and Medical Research Council
Funding Amount
$655,438.00
Summary
Gastric cancer (GC) is the second leading cause of cancer death worldwide, claiming the lives of >11,000 Australians from 1996-2006. Individuals diagnosed with GC have an expected 5-year survival rate of 10-30%. This could be improved if cases were identified in the early stages of the disease where treatments are more effective. Researchers from Adelaide and Melbourne are developing a diagnostic assay for early-stage GC based on a novel detection system that requires only a drop of blood.
Breast cancer is the most common cancer diagnosed in Australian women, affecting one in 8. While physical examination, mammography and ultrasound remain first-line screening tools, there are no reliable blood tests to aid diagnosis. This project aims to discover proteins in breast cancer tissue, or in the bloodstream of patients, which can be measured to provide information about the presence and severity of breast cancer. A new, reliable diagnostic test could benefit millions of women.
Proteomics Of Arthritis: Exploring Mechanisms Of Cartilage Degradation And Biomarker Identification
Funder
National Health and Medical Research Council
Funding Amount
$592,034.00
Summary
Arthritis is a major clinical and socio-economic problem. Arthritis involves the destruction of cartilage in joints. However, the mechanisms of initiation and progression of cartilage destruction remain poorly understood. Our studies will use new proteomic approaches to identify the changes in protein synthesis and degradation in mouse models of arthritis. This will provide critical information on disease mechanisms and for the development of diagnostic biomarkers and therapeutic approaches
Gonadotropin Inhibitory Hormone As A Major Regulator Of Reproduction In Mammals
Funder
National Health and Medical Research Council
Funding Amount
$623,378.00
Summary
Reproduction is controlled by the brain and it has been well established that gonadotropin releasing hormone (GnRH) is the primary stimulatory factor. GnRH stimulates the pituitary gland to produce and secrete hormones that, in turn, stimulate the ovaries and testes. It is becoming clear that the brain also produces an inhibitory factor and this project aims to establish that it (gonadotropin inhibitory hormone; GnIH) is functional in mammals.
The Nuclear Growth Hormone Receptor- Its Actions And Mechanism Of Nuclear Translocation
Funder
National Health and Medical Research Council
Funding Amount
$531,696.00
Summary
We and others have found that cell surface receptors for growth factors such as EGF, FGF and growth hormone can be found in the nucleus of proliferating cells. We have shown that many cancers have elevated nuclear GH receptor including leukemia, breast and colon cancer. If we artificially target the GH receptor to the nucleus, the resulting cells are tumorigenic when injected into immunocompromised mice, rapidly form ing metastasising tumours. To create more effective inhibitors of this tumourog ....We and others have found that cell surface receptors for growth factors such as EGF, FGF and growth hormone can be found in the nucleus of proliferating cells. We have shown that many cancers have elevated nuclear GH receptor including leukemia, breast and colon cancer. If we artificially target the GH receptor to the nucleus, the resulting cells are tumorigenic when injected into immunocompromised mice, rapidly form ing metastasising tumours. To create more effective inhibitors of this tumourogenesis, and to define the physiological roles of nuclear GH receptor, we will define the transport process which carries the receptor to the nucleus and block it. We will also seek to define how the receptor in the nucleus interacts directly with DNA to inhibit programmed cell death. To carry out these projects we will use sophisticated proteomics -mass spectrometry to identify the proteins interacting with the receptor in the transport and gene activation processes. The role of candidates will be tested by preventing their expression or by direct inhibition of their action using drugs or dominant negative versions. These approaches will provide leads to new anti-cancer therapeutics, and therapies for blocking diabetic blindness and kidney failure.Read moreRead less
Mechanisms Of Synaptic Vesicle Endocytosis Revealed By Its Regulatory Phosphoproteome
Funder
National Health and Medical Research Council
Funding Amount
$545,216.00
Summary
The nerve cells in our brains are in constant communication to sustain life. Communication involves electrical stimulation of one nerve cell which then responds by releasing chemical messengers, from vesicles, onto the next cell. Our research focuses on the mechanism of recycling of vesicles. Targeting this mechanism is a way to gain fundamental knowledge of how to intervene medically when communication fails, or when communication needs to be dampened, such as in some neurological diseases.
Analysis And Regulation Of Leptospiral Virulence Factors.
Funder
National Health and Medical Research Council
Funding Amount
$630,465.00
Summary
Leptospirosis is a globally important infectious disease caused by Leptospira spp. This project aims to identify and characterise factors which play a role in disease development by knocking out genes, then investigating the impact on overall gene-protein expression in the mutant strain and its ability to cause disease. This will allow us to gain insights on mechanisms by which Leptospira spp. cause disease, leading to development of better methods of disease control and prevention.
Outer Membrane Proteins Of Leptospira; Role In Immunity And Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$88,500.00
Summary
Leptospirosis is a significant cause of death in tropical regions of the world. Recent outbreaks in Nicaragua and Brazil are timely reminders of the seriousness of disease caused by the Leptospira bacteria. In these outbreaks >10% of people developing the disease did not recover. Spread of the disease does not occur from person to person, but rather from animal to human. Leptospira are shed from infected animals via the urine; human infection may occur through contact with infected urine or u ....Leptospirosis is a significant cause of death in tropical regions of the world. Recent outbreaks in Nicaragua and Brazil are timely reminders of the seriousness of disease caused by the Leptospira bacteria. In these outbreaks >10% of people developing the disease did not recover. Spread of the disease does not occur from person to person, but rather from animal to human. Leptospira are shed from infected animals via the urine; human infection may occur through contact with infected urine or urine contaminated materials. In Australia, leptospirosis is an occupational hazard with dairy farmers, pig handlers, banana pickers and abattoir workers being those most at risk. A recent and alarming development is the emergence of new risk groups associated with certain leisure activities. For example, in the USA three triathletes died from leptospirosis and it was subsequently determined that the source of infection was contaminated swimming water. This project will investigate aspects of the development of disease and immunity during infection by Leptospira. This will be achieved by analysing the set of proteins located on the surface of the bacterium. These proteins play a key role in the development of disease. Using state of the art technology, each of the proteins will be purified and identified. This will enable experiments that will enhance our understanding of the development of disease at a molecular level.Read moreRead less
CHARACTERISATION OF THE PROSTATE ANDROGEN-RESPONSE PROGRAM USING COMBINED TRANSCRIPT AND PROTEIN EXPRESSION PROFILING
Funder
National Health and Medical Research Council
Funding Amount
$232,200.00
Summary
Carcinoma of the prostate exhibits a wide range of biological variation influenced by genetic, racial, environmental, and other as yet undefined factors. For 1997 the Australian Bureau of Statistics estimates revealed that 27% of all deaths (> 34,000) were due to cancer. Among males, the second leading cause of death (13%) was prostate cancer. The development and progression of human prostate cancer is driven by the accumulation of genetic changes and influenced by a multitude of currently un ....Carcinoma of the prostate exhibits a wide range of biological variation influenced by genetic, racial, environmental, and other as yet undefined factors. For 1997 the Australian Bureau of Statistics estimates revealed that 27% of all deaths (> 34,000) were due to cancer. Among males, the second leading cause of death (13%) was prostate cancer. The development and progression of human prostate cancer is driven by the accumulation of genetic changes and influenced by a multitude of currently unknown events. In addition, a genetic predisposition to certain environmental elements may also provide susceptibility to the onset of prostate cancer. Inherent in identifying the mechanisms leading to prostate cancer is defining the molecular factors involved in the biological processes that influence the development, progression, and treatment of this malignancy. This proposal aims to address the lack of fundamental knowledge relating to the androgen hormone mediated molecular pathways through a comprehensive approach using genomic (DNA), transcribed (RNA) and translated (protein) information that will define the components of the androgen regulated events; i.e. identify the proteins and genes directly or indirectly regulated by androgenic hormones and their cognate receptors. Importantly we will apply technologies that can detect molecular changes in the cell without preconceived ideas about which information will be most valuable to monitor or which technologies will have the greatest impact. We anticipate that the characterisation of the prostate androgen-response will not only provide fundamental knowledge concerning androgen-mediated mechanisms of growth and cellular differentiation, but will also provide a molecular framework for therapeutic intervention through the identification of novel therapeutic targets suitable for a variety of interventions ranging from dietary modification to immunological and gene-therapy approaches.Read moreRead less