OVARIAN CANCER METASTASIS: Unraveling The Biology Of The Plasminogen Activation Cascade
Funder
National Health and Medical Research Council
Funding Amount
$169,875.00
Summary
Ovarian cancer affects 1,200 new Australians every year. Compared to breast cancer where research education and early screening have improved mortality rates, the incidence of ovarian cancer has not improved and death rates have more than doubled since 1930. With few overt symptoms, ovarian cancer has an extremely poor prognosis - a staggering 71% of women diagnosed with ovarian cancer will die from the disease, compared to 21% for breast cancer. Any studies which increase our understanding of t ....Ovarian cancer affects 1,200 new Australians every year. Compared to breast cancer where research education and early screening have improved mortality rates, the incidence of ovarian cancer has not improved and death rates have more than doubled since 1930. With few overt symptoms, ovarian cancer has an extremely poor prognosis - a staggering 71% of women diagnosed with ovarian cancer will die from the disease, compared to 21% for breast cancer. Any studies which increase our understanding of the biology of ovarian cancer metastasis may lead to new therapies designed to control these processes - as such this would be a major inroad into our fight against this cancer. The aim of this novel research project is to unravel the role that one cell surface system (the plasminogen (Plg) activation cascade) plays in determining the ability of ovarian cancer cells to metastasise and regulate new tumour blood vessel formation. This study addresses the paradoxical observations that this cascade can simultaneously facilitate cancer metastasis whilst concomitantly stopping new blood vessel formation in tumours. Using a number of advanced molecular cell biology methods, the hypothesis we will test is that the capacity of ovarian cancer to metastasise is determined by differential processing of plasminogen subsequent to cell-surface Plg binding. This results in a delicate balance between the generation of cell surface proteases and the release of protein fragments capable of stopping tumour blood vessel growth. Our group is well-equipped to address this hypothesis since we have already shown that: (1) Plg binding and activation is required for cancer cell invasion; (2) Plg binding and activation is elevated on malignant compared to benign cancers (3) Plg unfolds after it binds to cell surfaces or recombinant receptors; and, (4) Plg is easily fragmented to products that inhibit new blood vessel formation after binding to some cancer cells.Read moreRead less
Molecular Dissection Of The Munc18c:Syntaxin4 Complex Required For Insulin-regulated Exocytosis In Adipocytes
Funder
National Health and Medical Research Council
Funding Amount
$601,008.00
Summary
When blood glucose levels are high, insulin signals to fat and muscle cells to remove glucose from the blood. The uptake of glucose relies on membrane fusion events that deliver a specific glucose transporter protein to the cell surface in response to insulin signals. This process is affected in Type II diabetes. Our research will characterise the regulation of these membrane fusion events and will be important for understanding how insulin signals are communicated in health and disease.
A Tyrosine Phosphatase That Regulates Adherens Junctions, Cell Migration And The Epithelial-mesenchymal Transition
Funder
National Health and Medical Research Council
Funding Amount
$496,500.00
Summary
Cell-cell adhesion which physically glues cells together to form tissues and organs, also controls processes in development, wound healing and cancer progression. I have identified a novel regulator of cell-cell adhesion that regulates cell migration and cell morphology. Since these events are crucial during metastasis (the spread of cancer) and during wound healing, understanding the function of this novel regulator may provide the basis for new approaches to developing therapeutics. Specifical ....Cell-cell adhesion which physically glues cells together to form tissues and organs, also controls processes in development, wound healing and cancer progression. I have identified a novel regulator of cell-cell adhesion that regulates cell migration and cell morphology. Since these events are crucial during metastasis (the spread of cancer) and during wound healing, understanding the function of this novel regulator may provide the basis for new approaches to developing therapeutics. Specifically, in this proposal I aim to further our understanding of the function of this novel regulator in normal physiology and to elucidate how its functions are regulated.Read moreRead less
Neurotransmitter transporters are very good drug targets because modulation of their activity can lead to up and down regulation of neurotransmitter concentrations and thereby influence signalling pathways in the brain. This can be very useful in treating various neurological disorders and also altering normal brain functions such as learning and memory. In this project we will develop a detailed understanding of how glutamate transporters work and in so doing will be in a better position to des ....Neurotransmitter transporters are very good drug targets because modulation of their activity can lead to up and down regulation of neurotransmitter concentrations and thereby influence signalling pathways in the brain. This can be very useful in treating various neurological disorders and also altering normal brain functions such as learning and memory. In this project we will develop a detailed understanding of how glutamate transporters work and in so doing will be in a better position to design subtype and transporter-specific compounds. These compounds will be very useful in defining the role of glutamate transporter subtypes in normal and pathological states and may be useful in treating neurological disorders such as Alzheimer's disease, schizophrenia, ishaemia following a stroke, and motor neurone disease.Read moreRead less
Molecular Basis For RIG-I Like Receptor Activation Of The Innate Immune Pathway.
Funder
National Health and Medical Research Council
Funding Amount
$564,770.00
Summary
This project is to understand how proteins in the cell detect the presence of invading viruses, and pass on the message for the cell to produce defence molecules. The overproduction of these defence molecules can lead to inflammatory diseases. This research will help us to understand the process of the innate immune response in cells and how we might control it in disease states.