Plasmin is a complex enzyme that performs major roles in removal of blood clots, wound healing and in tumor metastasis. Here we will understand how plasmin function is regulated at the molecular level. These key insights will be of future use in the development of therapeutics targeting the plasmin system in cancer and clotting diseases.
Characterisation Of Two Novel Markers Of Osteosarcoma Metastasis As Potential Therapeutic Targets
Funder
National Health and Medical Research Council
Funding Amount
$624,500.00
Summary
Osteosarcoma (OS) is the most common bone tumour in children and adolescents. In spite of aggressive chemotherapy, OS tumours that metastasise to the lungs result in dismal long-term survivals of only 10-20%. For these patients, new treatment options are desperately needed. In this proposal we show compelling data identifying two new markers of OS metastasis. This research aims to validate the suitability of these novel markers as therapeutic targets to prevent OS metastasis.
Structural Studies On Human Glutamic Acid Decarboxylase
Funder
National Health and Medical Research Council
Funding Amount
$380,902.00
Summary
Mental health problems are a global issue and are subject to ongoing medical research. We study glutamic acid decarboxylase, a key enzyme responsible for the synthesis of a prominent and abundant neurotransmitter called GABA. GABA is crucial in controlling neuronal responses and facilitating new interconnections between neurones. Lacking GABA is related to epilepsy, Parkinson's disease, and post-traumatic stress. Our study is important for development of new ways to improve the supply of GABA in ....Mental health problems are a global issue and are subject to ongoing medical research. We study glutamic acid decarboxylase, a key enzyme responsible for the synthesis of a prominent and abundant neurotransmitter called GABA. GABA is crucial in controlling neuronal responses and facilitating new interconnections between neurones. Lacking GABA is related to epilepsy, Parkinson's disease, and post-traumatic stress. Our study is important for development of new ways to improve the supply of GABA in the brain.Read moreRead less
Activation And Inhibition Of The Plasminogen/Plasmin System
Funder
National Health and Medical Research Council
Funding Amount
$800,663.00
Summary
Plasmin is crucial enzyme present in blood plasma that functions in clot dissolution, inflammation, tissue remodeling, and wound healing. We aim to study how this enzyme system is controlled, by studying its interaction with receptors, co-factors and inhibitors. The information we gain will help drive the development of new generation therapeutics for the fine control of plasmin function in clotting disease, bleeding and inflammation.
Understanding How Bcl-2 Proteins Form The Apoptotic Pores That Kill Cells
Funder
National Health and Medical Research Council
Funding Amount
$893,614.00
Summary
Programmed cell death termed apoptosis is a process our bodies use to remove cells that are a threat to our health, e.g. cancer cells. The proteins that regulate cell death are attractive targets for therapeutics that have become resistant to this defence mechanism. This study will reveal how proteins from the Bcl-2 family regulate cell death at the molecular level. Understanding this process will inform the development of drugs aimed at regulating cell death in cancer and other diseases.
What Is The Molecular Mechanism Underlying Cell Death By Necroptosis?
Funder
National Health and Medical Research Council
Funding Amount
$653,742.00
Summary
Recently, we and others have demonstrated that part of the MLKL protein is able to kill cells. This process is known to cause a number of pathologies, including those arising from stroke. Blocking this type of cell death has thus emerged as an attractive therapeutic strategy. However, precisely how MLKL kills cells remains unclear and controversial. In this project, we will resolve these controversies with the goal of an increased fundamental understanding to aid drug discovery.
Generating Evidence Of Reduced Rates Of Overweight/obesity In Children: Value Adding To Four Established Australasian Early Intervention Trials
Funder
National Health and Medical Research Council
Funding Amount
$193,758.00
Summary
Childhood obesity is a major health problem. Trials are now being done to see whether helping families when their baby is young will reduce the rate of overweight children. We will combine data from these trials (1800+ children) to see if the programs work. To get maximum information we need to combine the line-by-line raw data from each patient in each trial. This is called an individual patient data meta-analysis. It is the best method for finding reliable answers to important health issues.
Structure-based Design Of Novel Therapeutics For Multi-drug Resistant Neisseria Gonorrhoeae
Funder
National Health and Medical Research Council
Funding Amount
$669,148.00
Summary
Multiple drug resistance (MDR) in bacteria represents one of the most intractable problems facing modern medicine. The recent superbug, MDR-Neisseria gonorrhoeae (MDR-Ng), causes the sexually transmitted infection gonorrhoeae. A multi disciplinary team with expertise in structural biology, medicinal chemistry and bacteriology will establish a comprehensive knowledge base aimed at developing new antibiotics to treat MDR-Ng by targeting a bacterial protein virulence factor.
Structural Characterisation Of The Co-inhibitory Complex Formed By The Tumour Suppressor PTEN And The Metastatic Factor PREX2
Funder
National Health and Medical Research Council
Funding Amount
$563,602.00
Summary
Metastasis is a major cause of cancer mortality. Characterisation of key proteins that regulate metastasis is therefore a priority. PTEN and PREX2 are enzymes that play key roles in metastasis in melanoma, and other cancers. We will determine the structural basis of PTEN:PREX2 co-inhibition, and determine how cancer-associated PREX2 mutations dysregulate this inhibitory complex. This study will provide the necessary knowledge for future drug development programs targeting PTEN:PREX2 in cancer.
Randomised Controlled Trial Of Surgical Skin Preparation For Prevention Of Superficial Wound Complications In Prosthetic Hip And Knee Replacement Surgery
Funder
National Health and Medical Research Council
Funding Amount
$403,128.00
Summary
The demand for prosthetic joint replacement surgery will double over the next decade. Complications involving the surgical wound are a devastating complication of this surgery. This randomised controlled trial aims to investigate whether skin cleansing prior to surgical incision with alcoholic iodine reduces the number of patients with superficial wound complications when compared to alcoholic chlorhexidine. The study will be performed in patients undergoing orthopaedic joint replacement surgery ....The demand for prosthetic joint replacement surgery will double over the next decade. Complications involving the surgical wound are a devastating complication of this surgery. This randomised controlled trial aims to investigate whether skin cleansing prior to surgical incision with alcoholic iodine reduces the number of patients with superficial wound complications when compared to alcoholic chlorhexidine. The study will be performed in patients undergoing orthopaedic joint replacement surgery: a high volume, high cost surgery.Read moreRead less