Investigation Of Two GPCRs Implicated In Tumour Progression: PAR1 And LGR5
Funder
National Health and Medical Research Council
Funding Amount
$404,689.00
Summary
G-protein-coupled-receptors (GPCRs) belong to a large and diverse family of membrane proteins. Due to their number, diversity and critical roles in signaling, GPCRs offer extraordinary opportunities for development of novel drugs. However, our rudimentary understanding of their mechanism of activation and subsequent signaling do not support rational drug design. This project focuses on two receptors, PAR-1 and LGR5, to gain insights into the activation mechanisms and signalling of GPCRs.
Molecular Determinants Of Drug Binding And Selectivity At Muscarinic Acetylcholine Receptors
Funder
National Health and Medical Research Council
Funding Amount
$816,866.00
Summary
G protein-coupled receptors (GPCRs) are the largest family of cell surface receptors in the human genome, and drugs targeting these receptors account for 30% of marketed drugs. This project aims to determine high resolution structural information on how drugs bind and specifically interact with GPCRs, which will enable future development of selective and effective drugs.
The Molecular Basis Of G Protein Coupled Transport
Funder
National Health and Medical Research Council
Funding Amount
$495,938.00
Summary
G proteins are molecular switches in all organisms, turning fundamental processes on and off . Defects in the functions of these switches can lead to severe diseases, such as cancer. Crucial details regarding the mechanism by which these switches are turned to on are still missing. This proposal will use a bacterial model system, with aims to provide structural and functional detail on the molecular mechanism of the switch in G proteins, and to extend this model to mammalian systems.
Structural And Functional Characterisation Of The Oncogene P-Rex1
Funder
National Health and Medical Research Council
Funding Amount
$623,447.00
Summary
The spread of cancer to other parts of the body (metastasis) is a major cause of mortality. The characterisation of proteins that regulate metastasis is therefore a priority. P-Rex1 plays a crucial role in promoting metastasis in breast and other cancers. We will determine the structural basis of P-Rex1 activity, and investigate how its dysregulation promotes aberrant cell growth. This study will provide the knowledge to build future drug development programs targeting P-Rex1 in cancer.
Peptide Toxins From Animal Venoms Specifically Targeting Voltage-gated Sodium Channels As Novel Analgesics And Pesticides
Funder
National Health and Medical Research Council
Funding Amount
$316,449.00
Summary
This project aims to understand how certain animal toxins that cause analgesic and pesticidal effects in model animals interact with biological ion channels in atomistic detail using computational techniques. By understanding the detailed molecular interactions involved in the binding of the toxins to channels, toxin variants with improved potency and specificity may be designed as promising templates for novel analgesics and pesticides.
Mechanisms Of Gene Regulation - Structure, Function And Design
Funder
National Health and Medical Research Council
Funding Amount
$697,209.00
Summary
The human genome contains at least 20000 genes. The activity of these genes must be tightly controlled throughout an individual’s life and problems with the regulation of genes lie at the heart of many common and serious diseases, including most forms of cancer. My program of research is focused on understanding the mechanisms underlying gene regulation and on the design of new reagents that could be used to manipulate the activity of genes that behave aberrantly in disease states.
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.
Oligomers Of The Alzheimer's Amyloid-? Peptide: Structure, Mechanism Of Toxicity And Small Molecule Interactions
Funder
National Health and Medical Research Council
Funding Amount
$356,324.00
Summary
Alzheimer’s disease is a devastating neurodegenerative disease that currently affects 240 000 Australians. The protein called amyloid-? is found in deposits in the brains of Alzheimer’s patients. The toxic form of this protein is thought to be small aggregated particles called ‘oligomers’. This work aims to investigate the structure of these particles, the reason why they are toxic, as well as their interaction with the neuroprotective compound EGCG, which is found in green tea.
Structural And Functional Analysis Of A Cancer-linked Co-regulator Complex
Funder
National Health and Medical Research Council
Funding Amount
$729,571.00
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.
Assembly And Function Of Two Interacting Oncogenic Scaffolds
Funder
National Health and Medical Research Council
Funding Amount
$705,585.00
Summary
Aberrant signaling by the protein kinase superfamily is a known driving force for many cancers and inflammatory diseases. Recently, a subset of kinase-like proteins, termed pseudokinases, have emerged as crucial regulators of kinase signalling pathways. This proposal focuses on elucidating the scaffolding function and assembly of two pseudokinases, termed SgK223 and SgK269, which display oncogenic properties and aims to understand how their signalling abilities are subverted in a disease state.