The critical role of the class III histone deacetylase SIRT2 in stabilizing N-Myc oncoprotein. Cancer is the commonest cause of death from disease in children. Neuroblastoma is the commonest solid tumor in early childhood. This project will investigate the critical roles of SIRT2 protein in increasing the expression of N-Myc oncoprotein and consequently inducing neuroblastoma, and SIRT2 inhibitors as anticancer agents.
Mitochondrially targeted anti-cancer drugs modulate the mitochondrial genome. Successful cancer management requires novel therapeutical approaches. This project will test the effect of a new class of compounds that target mitochondria, the powerhouse of the cells, where they suppress expression of mitochondrial genes. By this mechanism, cancers that are resistant to apoptosis induction can be inhibited.
How do mechanical cues regulate tissue renewal and tumour progression? Imbalances between cell production and cell death in tissues can be catastrophic, leading to major global health issues such as cancer. This project will use modified mice and protein-protein interaction based techniques to identify how changes in the mechanical properties of tissues regulate the balance between cell production and cell death.
A new Src, PKCdelta and Akt regulated protease activated receptor system in metastasis. In contrast with localised cancer which can often be cured, curative treatment is generally not possible for cancer that has spread. This project will characterise a protein that drives the spread of cancer and to develop new approaches to treat patients at risk of developing these aggressive tumours that spread to other organs.
Molecular hallmarks of androgen receptor targeting in prostate cancer. There is a critical need in oncology drug development for better biomarkers of response to prostate cancer therapies, clinically to assist with treatment decision making, and pre-clinically to facilitate translation of emerging agents into clinical practice. Using a unique explant culture model, this project will identify protein and lipid markers that can be used to accurately and reliably assess response to androgen recepto ....Molecular hallmarks of androgen receptor targeting in prostate cancer. There is a critical need in oncology drug development for better biomarkers of response to prostate cancer therapies, clinically to assist with treatment decision making, and pre-clinically to facilitate translation of emerging agents into clinical practice. Using a unique explant culture model, this project will identify protein and lipid markers that can be used to accurately and reliably assess response to androgen receptor (AR)-targeting therapies in human prostate tumours. The identification and functional assessment of these biomarkers will identify those that can be used as surrogate endpoints in clinical trials, facilitate earlier approval of investigational agents and lead to improved options for therapeutic management of prostate cancer.Read moreRead less
Crosstalk between breast cancer cells and the microenvironment to promote metastasis. Breast cancer spread (metastasis) to distant tissues is usually fatal. It is now clear that cross-talk between cancer cells and other normal cells is essential for metastasis and previous studies have discovered two key mechanisms: tumour cell suppression of immune defence pathways to escape immune recognition, and activation of proteases to promote invasion and blood vessel growth. Using unique models and cell ....Crosstalk between breast cancer cells and the microenvironment to promote metastasis. Breast cancer spread (metastasis) to distant tissues is usually fatal. It is now clear that cross-talk between cancer cells and other normal cells is essential for metastasis and previous studies have discovered two key mechanisms: tumour cell suppression of immune defence pathways to escape immune recognition, and activation of proteases to promote invasion and blood vessel growth. Using unique models and cellular imaging, this project aims to investigate the cell specific functions of these pathways and the therapeutic potential of altering their expression and function. This project may lead to the development of novel predictors of metastasis in patients and new targeted therapeutics to prevent breast cancer spread.Read moreRead less
Using Drosophila to analyse a master regulator of epithelial homeostasis. Aims:
This proposal aims to use genetic and cell biological analysis of the vinegar fly, Drosophila, to identify the function of the grainyhead gene in intestinal regeneration.
Significance:
This gene is conserved in all animal species and appears to be a master regulator of epithelial tissue development but it is unclear how it can both influence stem cell maintenance and production of functional cell types.
Expected out ....Using Drosophila to analyse a master regulator of epithelial homeostasis. Aims:
This proposal aims to use genetic and cell biological analysis of the vinegar fly, Drosophila, to identify the function of the grainyhead gene in intestinal regeneration.
Significance:
This gene is conserved in all animal species and appears to be a master regulator of epithelial tissue development but it is unclear how it can both influence stem cell maintenance and production of functional cell types.
Expected outcomes:
We will identify a new mechanism that governs tissue development, and introduce new imaging and genetic technologies to the Australian research community.
Benefit:
We expect potential economic and commercial interest in development of new gene analysis tools and biotechnological tissue manipulation applications.Read moreRead less
Peptide-based Star Polymers for Improved Biointeraction and Targeted Anticancer Therapies. The aim of this project is to develop peptide-based star polymer nanocarriers for targeted drug delivery to cancer stem cells which integrate aptamer targeting technology and biointeraction studies with blood plasma fluid. The significance of this research is it pioneers the development of a drug delivery system that minimises plasma opsonization through understanding polymer-plasma interactions, which in ....Peptide-based Star Polymers for Improved Biointeraction and Targeted Anticancer Therapies. The aim of this project is to develop peptide-based star polymer nanocarriers for targeted drug delivery to cancer stem cells which integrate aptamer targeting technology and biointeraction studies with blood plasma fluid. The significance of this research is it pioneers the development of a drug delivery system that minimises plasma opsonization through understanding polymer-plasma interactions, which in turn increases tumour specificity and cell internalisation through incorporation of targeting aptamers and triggered drug release. This project will use rational design, advanced macromolecular engineering and an interdisciplinary collaboration to generate next-generation polymer therapeutics for drug delivery.Read moreRead less
Understanding endocrine tumorigenesis - opportunities for new diagnostics and therapies. This project will generate new knowledge significant for improving cancer diagnosis and designing new therapies for cancer patients as we embrace the personalised medicine era. Specific focus is on endocrine tumours. This research has as its aim improved survival for people diagnosed with cancer.
Discovery Early Career Researcher Award - Grant ID: DE180101165
Funder
Australian Research Council
Funding Amount
$365,058.00
Summary
Structural insights into adenosine receptors. This project aims to investigate mechanisms underlying ligand binding and signal transduction at G protein-coupled receptors (GPCRs) by utilising the adenosine receptor family as a model system. This interdisciplinary project will use structural biology, pharmacology and biochemistry. The expected outcomes include understanding ligand selectivity across the four adenosine receptor family members. This should provide significant benefits, such as adva ....Structural insights into adenosine receptors. This project aims to investigate mechanisms underlying ligand binding and signal transduction at G protein-coupled receptors (GPCRs) by utilising the adenosine receptor family as a model system. This interdisciplinary project will use structural biology, pharmacology and biochemistry. The expected outcomes include understanding ligand selectivity across the four adenosine receptor family members. This should provide significant benefits, such as advancement of fundamental knowledge that could also lead to therapeutic development.Read moreRead less