Spatial And Temporal Dimensions Of Mu-opioid Receptor Signalling: Implications For The Development Of Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$799,316.00
Summary
The use of morphine as an analgesic is still limited by undesirable side effects such as tolerance. Despite decades of research, the mechanisms behind the development of tolerance are poorly understood. The ? opioid receptor is a protein expressed at the surface of the cells that is the target of morphine. This project will investigate the signalling events triggered by opioids with unprecedented resolution and will aim to elucidate why morphine elicits more tolerance than other opioid drugs.
Structural And Functional Analysis Of Oncostatin M Receptor Signalling Complexes
Funder
National Health and Medical Research Council
Funding Amount
$519,284.00
Summary
Understanding how a chemical messenger selectively controls bone formation may lead to development of new therapies for osteoporosis and potentially other important diseases.
Mitochondrial Quality Control In Parkinson’s Disease: The Molecular Mechanisms Of PINK1 And Parkin
Funder
National Health and Medical Research Council
Funding Amount
$558,721.00
Summary
Parkinson’s disease is a degenerative disorder of the central nervous system in which the underlying cause is mostly unknown. To pave the way to a better understanding of what goes wrong, this study will investigate the function of PINK1 and Parkin, two genes that are mutated in inherited forms of the disease that play important roles in maintaining cellular health. The results of this study will be used in exploring new therapeutic targets for the treatment of Parkinson’s disease symptoms.
This project investigates the way in which viruses are able to use host cell machinery to make viral proteins and to replicate their own genetic material. We focus on the picornavirus family that cause illnesses with important health and economic consequences including serious heart infections such as myocarditis and pericarditis as well as the "common cold". This research we will reveal new possible avenues of antiviral development.
Structure And Function Of A Cancer-linked Co-regulator Complex
Funder
National Health and Medical Research Council
Funding Amount
$1,282,475.00
Summary
We seek to understand the mechanisms by which genes are switched on and off throughout our lifetime. A number of multi-component protein machines are involved in this process but their make-up and mechanism of action is not understood. We will investigate the structure and function of one of these machines that has been strongly linked to cancer.
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 Stem Cell-specific MicroRNA-independent Function Of Drosha
Funder
National Health and Medical Research Council
Funding Amount
$637,702.00
Summary
Stem cells are responsible for producing and replenishing the ~200 specialised cell types in our body. Our goal is to understand the molecular switches that control the function of these cells. We recently discovered that the activity of certain genes within stem cells is controlled by degradation. This degradation is absolutely crucial for safeguarding the function of stem cells. This project will investigate how this novel mechanism is controlled within these cells.
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.
Assembly And Misassembly Of Mitochondrial Respiratory Chain Complex I
Funder
National Health and Medical Research Council
Funding Amount
$520,520.00
Summary
Mitochondria are the powerhouses in our cells. They burn the carbon fuels we eat and store the energy by making ATP that is used for functions such as muscle contraction and triggering of nerves. Mitochondrial Complex I is a molecular motor that helps to make ATP. “Mitochondrial disease” is often seen when Complex I is not built properly and this results in early childhood death. In this project we will study how Complex I is built and how the mitochondria responds to assembly problems.
Personalised Medicine For Mitochondrial Disorders: Targeting Pathogenic Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$1,770,213.00
Summary
Mitochondria are our cellular power plants that burn sugars, fats and proteins to generate energy. Each week in Australia a child is born with a mitochondrial disorder. Many of these children die in the first years of life and most suffer from severe disease, particularly affecting their brain and/or heart. We will use stem cell models to better understand the basic biology of these disorders and to develop targeted therapies to improve the outcomes for affected patients.