Molecular Basis For Stress-induced Gene Regulation—a Model System To Understand Transcriptional Deregulation In Cancer And Neurological Disease
Funder
National Health and Medical Research Council
Funding Amount
$384,076.00
Summary
Deregulated gene transcription plays a critical role in cancer formation. It is therefore important to understand the molecular basis of gene transcription and how tumour cells hijack the process. In this Project, we will study the molecular basis of stress-inducible gene expression. This is particularly important for understanding the molecular basis of cancer as stress-inducible genes are activated by transcription factors implicated in breast, colon, lung, and prostate cancers.
The dramatic increase in obesity and age-related metabolic disorders demonstrates the importance of gaining a better understanding of how cells and organisms regulate their energy stores. This project will identify novel molecular mechanisms that control the enzyme CaMKK2, which is a key regulator of whole-body energy metabolism. This will provide new opportunities to inform more effective strategies to tackle metabolic diseases, and improve health in an increasingly ageing population.
Understanding The Contribution Of Iron In Traumatic Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$601,263.00
Summary
Our group has discovered a novel role of amyloid precursor protein (APP) in cellular iron balance similar to another protein called ceruloplasmin (CP). Both, prevalently found in the brain, convert a damaging iron variety into the safer form. Disruption in either protein leads to cell death. We aim to establish how failure in APP and CP response may be detrimental to traumatic brain injury recovery. Understanding the iron role of APP and CP will lead to therapeutics to counter traumatic injury.
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.
Design And Engineering Of Adnectins For Diagnosis And Therapy
Funder
National Health and Medical Research Council
Funding Amount
$803,152.00
Summary
This project aims to engineer a naturally-occurring human protein, called an adnectin, to produce molecules that are able to bind specific targets in the human body, and as such may be used in the diagnosis and therapy of a range of diseases.
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.
Understanding The Function And Regulation Of G Protein-coupled Receptor Signalosomes And Their Role As High Resolution Signalling Platforms
Funder
National Health and Medical Research Council
Funding Amount
$566,588.00
Summary
G protein-coupled receptors are specialised proteins located on the surface of cells. They are the targets of 50% of currently available pharmaceuticals, but these drugs are derived from limited knowledge of only a fraction of proteins. This proposal will examine exciting and novel properties of receptors that only occur following the assembly of the proteins into specialised networks within cells. The new information will expand our current knowledge, and facilitate future targeted drug design.
Genomic Analysis Of DNA Binding And Gene Regulation By The Chromatin Remodelling Factor UBF
Funder
National Health and Medical Research Council
Funding Amount
$624,254.00
Summary
Synthesis of ribosomes, the cellular protein synthetic machinery, is the major anabolic event of a growing cell and is frequently dysregulated during disease such as cancer. This grant will examine a protein termed UBF that we think plays an important role in orchestrating the cellular response to dysregulated ribosome biogenesis. By understanding how UBF functions we hope to uncover novel therapeutic approaches to treat diseases associated with ribosome stress .
STABILISING G PROTEIN-COUPLED RECEPTORS FOR DRUG DISCOVERY
Funder
National Health and Medical Research Council
Funding Amount
$628,140.00
Summary
Prescription drugs targeting human proteins called GPCRs are sold as effective treatments for many diseases. However, there are over 800 different types of GPCRs in the human body and only a small fraction is targeted by drugs, mainly because GPCRs are unstable and thus difficult to work with in the laboratory. We are applying newly developed technologies to engineer stabilised ?1-adrenoceptors, a class of GPCRs, for drug discovery against cardiovascular diseases, epilepsy and neurodegeneration
Exploring Scanning Ultrasound (SUS), A Novel Method To Treat And Prevent Neurodegenerative Disease
Funder
National Health and Medical Research Council
Funding Amount
$765,708.00
Summary
We developed a novel scanning ultrasound (SUS) protocol that clears toxic protein aggregates and restores memory function in mouse models of Alzheimer's disease (AD), without the need for therapeutic agents. Here we aim to determine whether SUS has preventative potential, whether there are synergistic effects, and whether a therapeutic antibody combined with SUS leads to an enhanced therapeutic outcome. Together this will guide the development of an ultrasound therapy in AD patients.