Characterization Of SgK269, A Master Regulator Of Growth Factor Receptor Signalling
Funder
National Health and Medical Research Council
Funding Amount
$623,751.00
Summary
Perturbed signaling within a cell can cause multiple diseases, including cancer. SgK269 is a scaffold protein involved in signaling and implicated in breast, colon and pancreatic cancer. By determining the signaling mechanism and function of the SgK269 scaffold, this work will provide novel and important insights into a key regulator of cell signaling, and reveal potential strategies for therapeutic targeting of the SgK269 scaffold that could be utilized in cancer treatment.
Understanding Age-related Protein Aggregation. The Mechanism Of Cataract And Its Prevention
Funder
National Health and Medical Research Council
Funding Amount
$709,333.00
Summary
Cataract arises from clouding of the eye lens due to the aggregation of crystallin proteins whose high concentration and close packing facilitate lens transparency. This proposal will investigate crystallin structure and interactions to understand the reasons for cataract formation and its prevention via the design of aggregation inhibitors. The results will facilitate the development of drugs to prevent cataract and other related protein aggregation diseases, e.g. Alzheimer’s and Parkinson’s.
Investigating The Interaction Of Precursor Inner Membrane Proteins With Translocase Components
Funder
National Health and Medical Research Council
Funding Amount
$585,274.00
Summary
Proteins are synthesised on ribosomes located in the cellular plasm, and then moved to their site of action by specialised transport systems. Import of proteins to the mitochondria involves translocase pores, which come equipped with receptors and chaperones. We are investigating the targeting and transfer of newly synthesised proteins of the MCF carrier family from the ribosomal machinery to the inner mitochondrial membrane, focusing on interaction with chaperones in the intermembrane space.
Altered Nuclear Trafficking And Nuclear Body Dynamics As Drivers Of Ataxin-1 Toxicity
Funder
National Health and Medical Research Council
Funding Amount
$755,190.00
Summary
Ataxias are a large group of neurodegenerative disorders in which balance, motor skills and memory are progressively lost. While mutations in specific proteins do cause certain hereditary ataxias, the mechanisms of their detrimental actions is unclear. Our studies probe the toxic mechanisms of the ataxin-1 protein, focusing on its partners and stress-initiated formation of a toxic hydrogel state. The outcomes will define impacts on cellular protein movement in neurodegeneration more broadly.
Determining The Contribution Of Orexin Receptor Subtypes To Sleep Architecture
Funder
National Health and Medical Research Council
Funding Amount
$882,075.00
Summary
Sleep is an essential process that follows a regular pattern every night. The brain orexin system is a promising new target for sleep-inducing drugs; however it is not clear how best to manipulate this system to reproduce the cycles of sleep necessary to receive all the benefits sleep has to offer. This project will elucidate the contribution of the different components of the orexin system to the characteristics of sleep. This will facilitate the development of better treatments for insomnia.
Studying The Novel Role For G Protein-coupled Receptor Signalling In Leukaemia Development
Funder
National Health and Medical Research Council
Funding Amount
$373,144.00
Summary
Recent research has shown the clinical importance of abnormal stem cells (LSC) in acute myeloid leukaemia (AML). LSC are resistant to therapeutics suggesting that they could be a cause of relapse. Identifying signalling pathways that drive LSC development is essential to selectively eradicate LSC that could offer substantial therapeutic benefit. This proposal aims to identify and evaluate critical signalling pathways as a potential therapeutic target for developing effective novel LSC-targeted t ....Recent research has shown the clinical importance of abnormal stem cells (LSC) in acute myeloid leukaemia (AML). LSC are resistant to therapeutics suggesting that they could be a cause of relapse. Identifying signalling pathways that drive LSC development is essential to selectively eradicate LSC that could offer substantial therapeutic benefit. This proposal aims to identify and evaluate critical signalling pathways as a potential therapeutic target for developing effective novel LSC-targeted therapy in AML.Read moreRead less
IRON EXPORT PROTEIN FAILURE IN PARKINSONISM AND DEMENTIA
Funder
National Health and Medical Research Council
Funding Amount
$843,352.00
Summary
We recently discovered a novel relationship between the Alzheimer’s amyloid precursor protein (APP) and tau, and that both proteins play a role in regulating iron levels in the brain. We predict that a loss or multiple failures in these iron-regulating systems could foster a toxic iron accumulation in brain, leading to the development of diseases with dementia such as Alzheimer’s and Parkinson’s diseases. We hope to gain a better understanding of their mechanism of action and propose that this p ....We recently discovered a novel relationship between the Alzheimer’s amyloid precursor protein (APP) and tau, and that both proteins play a role in regulating iron levels in the brain. We predict that a loss or multiple failures in these iron-regulating systems could foster a toxic iron accumulation in brain, leading to the development of diseases with dementia such as Alzheimer’s and Parkinson’s diseases. We hope to gain a better understanding of their mechanism of action and propose that this pathway is a target for therapeutic intervention.Read moreRead less
Unravelling The Binding And Activation Mechanism Of A Complex G Protein-coupled Receptor
Funder
National Health and Medical Research Council
Funding Amount
$1,041,638.00
Summary
The peptide hormone relaxin is currently in a Phase III trial for the treatment of heart failure. However the peptide is not a good drug as it can't be taken orally and is very expensive to produce. We will study the interaction of relaxin with its cell surface receptor and the mechanisms by which the receptor functions. The knowledge gained will aid in the design of smaller, more potent and orally active forms of relaxin for the treatment of heart failure
Determining Modes Of Binding And Activation Of Complex G-protein Coupled Receptor Targets
Funder
National Health and Medical Research Council
Funding Amount
$620,399.00
Summary
The peptide hormones relaxin is currently in a Phase III trial for the treatment of heart failure. However the peptide is not a good drug as it can't be taken orally and is very expensive to produce. We will study the interaction of relaxin and the related peptide INSL3 with their cell surface receptors and the mechanisms by which the receptors function. The knowledge gained will aid in the design of smaller, more potent and orally active forms of relaxin which will be able to be used as drugs f ....The peptide hormones relaxin is currently in a Phase III trial for the treatment of heart failure. However the peptide is not a good drug as it can't be taken orally and is very expensive to produce. We will study the interaction of relaxin and the related peptide INSL3 with their cell surface receptors and the mechanisms by which the receptors function. The knowledge gained will aid in the design of smaller, more potent and orally active forms of relaxin which will be able to be used as drugs for the treatment of heart failure.Read moreRead less
The Role Of Beta-Amyloid Precursor Protein And Tau In The Regulation Of Neuronal Iron
Funder
National Health and Medical Research Council
Funding Amount
$650,226.00
Summary
We have recently discovered a novel relationship between amyloid precursor protein (APP) and tau in regulating neuronal iron balance. This project will establish how tau aids APP transport to the cell surface where it assists cellular iron release. A commonality in some neurodegenerative diseases are disruptions in either proteinsÍ function and iron-related excitotoxicity. Understanding the iron role of APP and tau will lead to a therapeutic mechanism of action and better future drug design.