Trafficking Mechanisms Governing Receptor Availability For Signalling
Funder
National Health and Medical Research Council
Funding Amount
$526,978.00
Summary
Receptors on the cell surface allow cells to respond to their environment. We have recently discovered a new pathway for controlling the amount of receptors displayed on the cell surface, errors within which will lead to defects in development and diseases like cancer. We are studying how this new pathway controls the balance between how much receptors are destroyed after being activated and how much are recycled back for re-use.
An Integrated Systems Biology Approach For The Development Of New Therapeutic Strategies For The Treatment Of High Grade Glioma
Funder
National Health and Medical Research Council
Funding Amount
$696,404.00
Summary
Glioma, the most common adult brain cancer, is incurable. Recent advances now allow us to grow glioma cells directly from patients in the laboratory in a way that preserves the features of the original tumor. In this proposal we will systematically analyze such cells using state-of-the-art technologies to identify new processes important to glioma, which in turn should facilitate the identification of innovative therapeutic approaches.
Overcoming Receptor Tyrosine Kinase Mediated Resistance To BRAF Inhibitors In Metastatic Melanoma, Colorectal And Lung Cancers.
Funder
National Health and Medical Research Council
Funding Amount
$574,958.00
Summary
The drug Vemurafenib results in good responses in melanoma patients. However, patients become resistant to treatment. We have identified specific receptors that can cause Vemurafenib resistance, which can be overcome by combination treatment with drugs to these receptors. We will assess melanoma patient samples for expression of these receptors which will be highly beneficial for selecting combination treatments to prevent drug resistance and ensure better prolonged outcomes.
A New Master Adaptor Protein For Toll-like Receptor Signalling
Funder
National Health and Medical Research Council
Funding Amount
$869,288.00
Summary
Certain proteins on the surface of cells are able to sense danger and infection. These receptors use adaptor proteins to enable cells to respond appropriately. We have discovered a new adaptor that controls receptor signalling in inflammation. This new master adaptor likely has widespread roles in infection and inflammation. We aim to understand how this adaptor works, and to identify ways of blocking its actions. These studies may help us to control inflammation underpinning many diseases.
Neurons are highly compartmentalized cell-types. In neurodegenerative diseases such as Alzheimer's disease, the protein Tau that serves a distinct function in one cellular compartment (the axon) accumulates in a massively phosphorylated form elsewhere (somatodendritic compartments and their spines) which is believed to impair neuronal functions. We will investigate how Tau is distributed in health and disease, and determine how this distribution is regulated.
Targeting The EGFR And C-Met Tyrosine Kinase Receptors In Myeloproliferative Neoplasms
Funder
National Health and Medical Research Council
Funding Amount
$607,559.00
Summary
We propose that in the blood disorders called Myeloproliferative Neoplasms (MPN) there are important changes that affect the function of receptors expressed on the surface of blood cells. These changes will perturb blood cell production and may be able to be targeted effectively with drugs. We will test this using laboratory-based and mouse models of MPN, together with specific drugs that are currently in the clinic, and that inhibit the activity of the key receptors involved. This approach can ....We propose that in the blood disorders called Myeloproliferative Neoplasms (MPN) there are important changes that affect the function of receptors expressed on the surface of blood cells. These changes will perturb blood cell production and may be able to be targeted effectively with drugs. We will test this using laboratory-based and mouse models of MPN, together with specific drugs that are currently in the clinic, and that inhibit the activity of the key receptors involved. This approach can be rapidly translated to clinical trial.Read moreRead less
Targeting FLT3 Kinase Activity To Treat Haematopoietic Neoplasms
Funder
National Health and Medical Research Council
Funding Amount
$673,045.00
Summary
Most leukaemias are incurable so it is important to find new treatments. For this to occur it is essential that the mutated genes that cause leukaemia are identified. We have generated a mouse with a mutation in a gene called c-Cbl that promotes the activation a protein called FLT3 that is involved in the development of many types of leukaemias. By treating mutant mice a drug that specifically suppresses the function of FLT3 we intend to identify the most effective treatments for human leukaemia ....Most leukaemias are incurable so it is important to find new treatments. For this to occur it is essential that the mutated genes that cause leukaemia are identified. We have generated a mouse with a mutation in a gene called c-Cbl that promotes the activation a protein called FLT3 that is involved in the development of many types of leukaemias. By treating mutant mice a drug that specifically suppresses the function of FLT3 we intend to identify the most effective treatments for human leukaemias associated with activated forms of FLT3.Read moreRead less
Understanding Intrinsic And Acquired Resistance To Anti-FGFR Therapies
Funder
National Health and Medical Research Council
Funding Amount
$797,051.00
Summary
In vitro and in vivo preclinical data suggests that inhibition of FGFR in endometrial cancer patients may be a viable therapeutic approach. Data from other cancers suggests that despite remarkable initial responses to kinase inhibitors, cancer cells eventually develop resistance. This project aims to identify and characterize the mechanisms of resistance that emerge following FGFR inhibition in order to design combination therapies that may delay and/or prevent the emergence of resistance.
MicroRNAs And Their Processing Complexes Integrate ErbB-2 And AR Signaling Pathways In Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$660,665.00
Summary
Prostate cancer is the most common cancer in men and is dependent upon signaling from male hormones (androgens) for continued growth. We recently identified some novel small RNAs (intracellular messengers), called microRNAs, that are likely to play important roles in the growth of prostate cancer cells. This project will evaluate the functional role of these microRNAs in human prostate cancer, as well as some other proteins involved in microRNA processing and may provide the foundation for new a ....Prostate cancer is the most common cancer in men and is dependent upon signaling from male hormones (androgens) for continued growth. We recently identified some novel small RNAs (intracellular messengers), called microRNAs, that are likely to play important roles in the growth of prostate cancer cells. This project will evaluate the functional role of these microRNAs in human prostate cancer, as well as some other proteins involved in microRNA processing and may provide the foundation for new avenues for therapeutic intervention.Read moreRead less
Structural Events In Insulin And IGF Signalling - A Nanodisc Approach To A Problem In Cancer, Diabetes And Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$752,403.00
Summary
Insulin and its insulin-like growth factors play a major role in three major disease states facing ageing Australians—diabetes, cancer and Alzheimer's disease. We aim to understand how these proteins send messages into cells via their so-called receptors. We will isolate the receptor molecules from cells and then image them in an advanced electron microscope to produce three-dimensional images. Our findings will have implications for the design of therapeutics targeting the above three diseases.