MicroRNAs are small molecules that modulate the expression of most genes and so affect nearly every biological process and pathology although, they were only discovered in humans less than 10 years ago. The bottleneck in discovering the functions of miRNAs is in identifying their molecular targets, the majority of which remain unknown. We aim to comprehensively identify direct target genes of epithelial-specific microRNAs and to confirm a number of them by gene target validation approaches.
Role Of The MiR-200 Target Quaking In Alternative Splicing During EMT And Cancer Progression
Funder
National Health and Medical Research Council
Funding Amount
$443,160.00
Summary
The spread of cancer to other organs involves cancer cells changing to a more aggressive state and is a major cause of cancer related death. MicroRNAs are a class of genes that control whether cancer cells become more aggressive by regulating other genes. In this project we will examine the function of a new microRNA target which controls the cancer cell aggression. The outcome will be a better understanding of how cancers spread and the identification of new therapeutic targets.
Glucose is a critical fuel for living organisms and its presence in the gut triggers nerves that slow stomach emptying. However, little is known of how glucose is actually detected in the gut. We have established that sweet taste molecules of the tongue are also present in the gut, where they may detect glucose. This research will measure the expression and function of these molecules in the gut of humans and mice, and reveal key information on their potential as targets in health and disease.
Exploiting Increased Autophagy In Bronchial Epithelial Cells: A New Therapeutic Approach For Chronic Obstructive Pulmonary Disease (COPD)
Funder
National Health and Medical Research Council
Funding Amount
$724,161.00
Summary
COPD is incurable, a leading cause of death, and new therapies are urgently needed. Autophagy is a cell response to cell stress conditions, however increased autophagy is harmful. We will investigate the association of increased autophagy with COPD and smoking and evaluate therapies that can reduce autophagy, including zinc-related drugs and novel antibiotics that have been modified to lose their anti-bacterial activity.
Targeting MicroRNA-driven Mesenchymal To Epithelial Transition To Suppress Prostate Cancer Metastasis
Funder
National Health and Medical Research Council
Funding Amount
$741,831.00
Summary
Prostate cancer kills ~3,000 men per year in Australia. The development of metastasis is the major cause of prostate cancer-associated death and has limited treatment options. In this study, we will characterise the role of a group of molecules, termed microRNAs, in prostate cancer metastasis. We will also test whether targeting microRNAs using novel drugs termed antagomiRs is an effective strategy to inhibit metastasis and thereby improve prostate cancer mortality.
Characterising Novel Alternative Splicing Networks That Promote Tumour Cell Plasticity
Funder
National Health and Medical Research Council
Funding Amount
$609,329.00
Summary
During cancer progression, tumour cells can change their properties and become more aggressive and resistant to therapies. We have identified an important regulator of this tumour cell transition, called “Quaking”, which causes widespread changes in gene splicing. We aim to investigate how "Quaking" causes changes in gene splicing and what the effects of these splicing changes are in tumour cells.
Regulation Of VEGFR Trafficking And Signal Transduction By The Ubiquitin Ligase Nedd4
Funder
National Health and Medical Research Council
Funding Amount
$388,347.00
Summary
Our recent work has discovered that the Nedd4 gene is crucial for the growth and development of blood vessels and lymphatic vessels. Our data suggest that Nedd4 controls vessel growth by regulating the levels and signalling activity of the key vascular growth factor receptors VEGFR-2 and VEGFR-3. The goals of this proposal are to define precisely how Nedd4-1 regulates the activity of these receptors and how VEGFR signalling could be better targeted to treat vascular disorders.
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.
Defining the spatial and temporal regulation of neurite branching. This project aims to identify mechanisms via which the cytoskeleton regulates the branching of nerve cell extensions. The formation of branched cell extensions is essential for establishing a complex network of connecting and communicating nerve cells in all higher organisms. This project expects that by combining advanced light microscopy technology and recently developed tools for the study of the cell architecture in vitro and ....Defining the spatial and temporal regulation of neurite branching. This project aims to identify mechanisms via which the cytoskeleton regulates the branching of nerve cell extensions. The formation of branched cell extensions is essential for establishing a complex network of connecting and communicating nerve cells in all higher organisms. This project expects that by combining advanced light microscopy technology and recently developed tools for the study of the cell architecture in vitro and in vivo, we will be able to define the molecular changes in neurites that control neurite branching. This should provide significant benefits, such as gaining crucial insights into the mechanisms of forming complex neuronal networks.Read moreRead less
Transcription factor nuclear residency as a driver of gene expression. Persistently active proteins can stay in the nucleus to drive cell growth and prevent cell death. This project will define how one specific active protein can remain in the nucleus and regulate gene expression through the action of unique ribonucleic acid (RNA) molecules. The results will enable persistent gene activation to be manipulated in cancer.