Regulatory Mechanisms And Roles Of Calpains In Skeletal Muscle
Funder
National Health and Medical Research Council
Funding Amount
$439,813.00
Summary
The objectives are to understand the regulation and roles of calpains, which are proteases that break proteins in the building and repair of skeletal muscle. We will determine targets that calpains cleave and whether their location changes following activation, as well as the cellular factors regulating their activity. In addition, we will obtain information about the specific type of calpain dysfunction that occurs in particular patients with limb girdle muscular dystrophy 2A.
Kallikrein Proteases Have Key Functional Roles In Peritoneal Invasion And Chemoresistance In Epithelial Ovarian Cancer
Funder
National Health and Medical Research Council
Funding Amount
$815,541.00
Summary
Only 30% of ovarian cancer patients with advanced disease survive for 5 years. This is because the cancer quickly spreads into the abdominal cavity and often becomes resistant to chemotherapy. We aim to use a new 3D culture system, mouse models and novel inhibitors to study the roles of 4 kallikrein enzymes in these events. The outcomes from this study will lead to a better understanding of the role of kallikreins in ovarian cancer and may lead to new treatment approaches.
Functional Analysis Of The Roles Of The Serine Protease Kallikrein 7 And Its Variant Isoform In Serous Ovarian Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$509,017.00
Summary
Ovarian cancer is the leading cause of death from gynaecological cancers with 1,200 women in Australia diagnosed with the disease in 2004, and 852 patients dying of ovarian cancer. The mortality rate has improved little over the last two decades with one of the major reasons being that ovarian cancer is often diagnosed at a late stage when cancer cells have spread into the abdomen or metastasised to other sites. The kallikrein family of serine proteases or enzymes is emerging as very useful diag ....Ovarian cancer is the leading cause of death from gynaecological cancers with 1,200 women in Australia diagnosed with the disease in 2004, and 852 patients dying of ovarian cancer. The mortality rate has improved little over the last two decades with one of the major reasons being that ovarian cancer is often diagnosed at a late stage when cancer cells have spread into the abdomen or metastasised to other sites. The kallikrein family of serine proteases or enzymes is emerging as very useful diagnostic or prognostic biomarkers for ovarian cancer as they often have higher levels in ovarian cancer tissue compared to the normal ovary. One of these enzymes is kallikrein 7, which is also involved in shedding of skin cells. Because of its involvement in skin, we hypothesise it may be playing a similar role in ovarian cancer and helping the cancer cells to detach from the ovary so they are free to move around the body to other sites. There are two different forms of kallikrein 7, a long form and a shorter form which is lacking a part that is crucial to enzymatic activity. While low levels of the short form have been found in normal ovary, very high levels of both forms were seen in ovarian cancer, especially the serous subtype which is the most common and most aggressive form of ovarian cancer. The aim of this project is to determine the function(s) of both forms of kallikrein 7 in ovarian cancer and to identify other molecules-proteins they are involved with. These findings will tell us if kallikrein 7 is involved in the spreading of ovarian cancer cells or metastasis and will lead to a better understanding of the development and progression of ovarian cancer. The finding from this study may also lead to better therapeutic approaches (ie blocking the action of Kallikrein 7), and-or markers to monitor ovarian cancer progression.Read moreRead less
Control Of Mast Cell Tryptase Function In Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$302,627.00
Summary
Allergic disorders such as anaphylaxis, eczema, hay fever and asthma affect about 25% of the developed world. Australia has one of the highest asthma prevalence in the world, costing Australians about a billion dollars a year. One of the central players in allergies is the mast cell enzyme, ?-tryptase. We have discovered a new mechanism of control of this enzyme. This research will aid the development of specific and potent inhibitors of ?-tryptase for the treatment of allergic disorders.