Targeting The Sympathetic Nervous System To Reduce The Burden Of Fatty Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$728,152.00
Summary
The metabolic syndrome is characterised by abdominal obesity, high blood pressure and an increased risk of diabetes development. It is clear from our own observations that the sympathetic nervous system (SNS) is important in the generation of obesity-related illness and, through its stimulation of the liver, plays an important role in the development of obesity-related liver disease. We will target the SNS in order to reduce the burden of obesity-related liver disease.
MINIMAL RESIDUAL DISEASE IN ACUTE LYMPHOBLASTIC LEUKAEMIA
Funder
National Health and Medical Research Council
Funding Amount
$455,204.00
Summary
This project will study the extremely small numbers of leukaemic cells which are found in patients who are apparently healthy, but which sometimes lead to relapse. Very sensitive methods for measuring and studying low levels of leukaemic cells will be developed and used. To develop new better treatments in the long term, we will study why current treatment sometimes fails to eradicate the leukaemia, leading to patients relapsing. Clinicians currently need to obtain samples of bone marrow to asse ....This project will study the extremely small numbers of leukaemic cells which are found in patients who are apparently healthy, but which sometimes lead to relapse. Very sensitive methods for measuring and studying low levels of leukaemic cells will be developed and used. To develop new better treatments in the long term, we will study why current treatment sometimes fails to eradicate the leukaemia, leading to patients relapsing. Clinicians currently need to obtain samples of bone marrow to assess leukaemia, and the research will show whether this needs to be continued, or whether, with sensitive tests, samples of blood can be used instead. The study will involve collaboration with clinicians throughout Australia and overseas.Read moreRead less
Do The Mitochondrial Sirtuin Enzymes, SIRT3 And SIRT5, Affect Insulin Action In Skeletal Muscle?
Funder
National Health and Medical Research Council
Funding Amount
$92,314.00
Summary
Metabolic disorders such as obesity, insulin resistance and type 2 diabetes are characterised by inappropriate handling of nutrients. Mitochondria are the primary site for nutrient oxidation in cells. Sirtuins such as SIRT3 and SIRT5 are abundant in mitochondria and may affect mitochondrial function and insulin action in skeletal muscle. Understanding the biochemical pathways involved in energy metabolism in skeletal muscle is crucial in the development of therapies for insulin resistance and ty ....Metabolic disorders such as obesity, insulin resistance and type 2 diabetes are characterised by inappropriate handling of nutrients. Mitochondria are the primary site for nutrient oxidation in cells. Sirtuins such as SIRT3 and SIRT5 are abundant in mitochondria and may affect mitochondrial function and insulin action in skeletal muscle. Understanding the biochemical pathways involved in energy metabolism in skeletal muscle is crucial in the development of therapies for insulin resistance and type 2 diabetes.Read moreRead less
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.
Tailoring Targeted Therapy To DNA Repair-defective High-Grade Serous Ovarian Cancer
Funder
National Health and Medical Research Council
Funding Amount
$802,247.00
Summary
Ovarian cancer is a major cause of cancer death in women because current treatments are inadequate. Half of aggressive ovarian cancers have abnormalities in DNA repair and should be susceptible to new PARP inhibitor therapy, yet not all those respond. By developing a new model of studying human ovarian cancers in mice, we can discover markers to predict which ovarian cancers will respond best to these exciting new treatments.
Multi-Targeted Inhibition Of An Essential Tetrameric Enzyme From Drug -Resistant Streptococcus Pneumonie.
Funder
National Health and Medical Research Council
Funding Amount
$534,313.00
Summary
Streptococcus pneumoniae is an significant human pathogen which causes several diseases including pneumonia and meningitis. Treatment of infection involves the use of antibiotics such as penecillin, however, resistant strains are now emerging. This project will address the real need to develop new antibiotics targeting this organism. This is essentially a drug discovery project which exploits a novel means to target Streptococcus pneumoniae.
Mechanism Of Action Of Sec1p-like Proteins In Membrane Trafficking.
Funder
National Health and Medical Research Council
Funding Amount
$440,250.00
Summary
One of the most important evolutionary changes that has occurred is the development of intracellular compartments. All eukaryotic cells possess numerous membrane-encased structures which provide the basis for intracellular specialisation. For example, in order to degrade unwanted components cells have developed degradative enzymes. It is vital for the cell that these enzymes are sequestered away from other cellular components to avoid destruction of valuable molecules. In addition, the cell has ....One of the most important evolutionary changes that has occurred is the development of intracellular compartments. All eukaryotic cells possess numerous membrane-encased structures which provide the basis for intracellular specialisation. For example, in order to degrade unwanted components cells have developed degradative enzymes. It is vital for the cell that these enzymes are sequestered away from other cellular components to avoid destruction of valuable molecules. In addition, the cell has developed a complex assembly line of modifications that are added to proteins in a specific order as they travel to their final destination within the cell. This necessitates the accurate passage of molecules between compartments, a process known as vesicle transport. To orchestrate the complex network of vesicular transport steps between all of the various intracellular compartments it is necessary to employ complex machinery to guide and check that these steps occur with high fidelity. The goal of our research proposal is to define the function of one of the molecules involved in this control process, the so-called Sec1p proteins. The strength of our proposal lies in the diversity of our approach. We intend to explore the molecular advantages of a relatively simple eukaryotic organism, a yeast cell, and apply the findings obtained from this cell to a more complex but highly related vesicular transport process; that of the insulin-regulated movement of a glucose transporter in mammalian fat and muscle cells. While we intend to apply our findings to the treatment of patients with diabetes, it is our ultimate goal to be able to learn more about this fundamental cell biological process so that we can apply our knowledge to understanding many different disease states.Read moreRead less
Once treatable infections are becoming deadly because bacteria are developing broad antibiotic resistance. New medicines are urgently needed. Microbes themselves are the richest known source of new antibiotics but finding the 'good bugs' is like finding a needle in a microbial haystack. This project will use state-of-the art science to screen a previously overlooked source of rich microbial biodiversity and find new antibiotics.
This research proposal will identify changes in liver-secreted proteins during the development of fatty liver, and in the transition from fatty liver to the more advanced form of liver disease, non-alcoholic steatohepatitis (NASH). Understanding the differences in protein secretion between NASH patients and patients with normal/fatty liver will provide the opportunity to identify disease biomarkers that could be determined from a blood sample. This will provide a major shift in clinical care.
Sphingosine Kinase: A Target For Obesity-induced Insulin Resistance
Funder
National Health and Medical Research Council
Funding Amount
$626,845.00
Summary
Insulin resistance, a characteristic of type 2 diabetes, is linked to abnormal metabolism of lipid (fat) in tissues such as liver and muscle. This project aims to identify a novel pathway which may promote a build up of lipids in liver and therefore leads to the development of type 2 diabetes. This work may provide a basis for understanding and optimizing treatment of insulin resistance by regulating the control of fat metabolism in liver.