Drugging the undruggable: Development of novel technologies to selectively regulate the expression of targets driving cancer and other diseases. Transcription factors are “undruggable” targets playing a principal role driving cancer. This project will create novel therapeutic strategies to inhibit transcription factors and other elusive targets differentially expressed in diseased cells, without affecting normal tissue. It proposes to construct engineered proteins able to bind and modify specifi ....Drugging the undruggable: Development of novel technologies to selectively regulate the expression of targets driving cancer and other diseases. Transcription factors are “undruggable” targets playing a principal role driving cancer. This project will create novel therapeutic strategies to inhibit transcription factors and other elusive targets differentially expressed in diseased cells, without affecting normal tissue. It proposes to construct engineered proteins able to bind and modify specific key genes deregulated in cancer, to correct their expression and stably reprogram the phenotype of the tumour cell in a normal-like state. It outlines the engineering of novel synthetic agents to block specific protein-protein interactions in cancer cells and to induce potent tumour cell death. This work will generate novel and selective therapeutics to treat un-curable forms of tumours.Read moreRead less
Genomic and molecular characterisation of a novel Australian leishmania pathogen. Leishmaniasis is the second most serious protozoal disease after malaria. This project will help characterise the first Leishmania species identified in Australia providing molecular tools to monitor the pathogen and a detailed assessment of any potential risk to human health. Comparative analysis with more pathogenic species will help identify genes and mechanisms that determine the progression of human disease le ....Genomic and molecular characterisation of a novel Australian leishmania pathogen. Leishmaniasis is the second most serious protozoal disease after malaria. This project will help characterise the first Leishmania species identified in Australia providing molecular tools to monitor the pathogen and a detailed assessment of any potential risk to human health. Comparative analysis with more pathogenic species will help identify genes and mechanisms that determine the progression of human disease leading to the potential identification of new drug and vaccine targets. The methodologies and expertise developed will be used will be available to other research groups working on infectious diseases.Read moreRead less
Novel Statistical Methods For Genetic Epidemiology
Funder
National Health and Medical Research Council
Funding Amount
$481,505.00
Summary
We are in the midst of a genomics revolution that is transforming epidemiology, medicine and drug discovery. However, the scarcity of sophisticated statistical techniques to deal with the complicated problems inherent in genetic investigations of complex diseases is currently the critical factor limiting the success of human gene discovery programs. Statistical genetic methodology is currently one of the fastest developing areas of epidemiology. In information-intensive' areas such as genetic ep ....We are in the midst of a genomics revolution that is transforming epidemiology, medicine and drug discovery. However, the scarcity of sophisticated statistical techniques to deal with the complicated problems inherent in genetic investigations of complex diseases is currently the critical factor limiting the success of human gene discovery programs. Statistical genetic methodology is currently one of the fastest developing areas of epidemiology. In information-intensive' areas such as genetic epidemiology, genomics, and proteomics, there is a high demand for data analysis and statistical skills. WA has some world class expertise in statistical science, both in academia and in industry. However, this expertise has not yet been applied in a system way to genetic data analysis. We propose to undertake advanced methodological research in statistical genetics and bioinformatics, to produce easy-to-use and accessible software tools and resources that allow methodological advances to be accessed by the Australian research community, and to apply our new methods and tools both to specific disease research and to the developing human genome epidemiology (HuGE) enterprise in WA. These new initiatives in methodological research will draw together a number of currently separate research strands and will provide new tools and resources that will allow applied Australian programs to improve the efficiency of their research into the causes of important. Methodological development in both bioinformatics and statistical genetics are recognized international areas of need.Read moreRead less
Coproantigen detection tests for diagnosis of intestinal parasitic nematode infection. The aim of this project is to develop new tests for detection of hookworm and Strongyloides, two common intestinal worm infections of humans. These tests offer the potential to replace current tests, namely stool microscopy and serodiagnosis, both of whose performance is unsatisfactory due to deficiencies in sensitivity, specificity and operator convenience. The tests will rely on monoclonal antibodies to dete ....Coproantigen detection tests for diagnosis of intestinal parasitic nematode infection. The aim of this project is to develop new tests for detection of hookworm and Strongyloides, two common intestinal worm infections of humans. These tests offer the potential to replace current tests, namely stool microscopy and serodiagnosis, both of whose performance is unsatisfactory due to deficiencies in sensitivity, specificity and operator convenience. The tests will rely on monoclonal antibodies to detect parasite products in stool. Such testing technology is amenable to configuration in a robust format, suitable for large-scale manufacture. Given the worldwide prevalence of these parasites, the tests will have a market potential of international significance.Read moreRead less
Development of class-leading bioluminescence resonance energy transfer technologies for real-time monitoring of molecular interactions. The purpose of this project is to develop improved technologies for identifying and developing pharmaceuticals with fewer side effects. The expected outcome is the development of technologies that provide a level of sensitivity and data quality that enables adoption by the biotechnology and pharmaceutical industries.
Rapid mapping of genes for complex traits. This project will develop a new resource that will allow rapid identification of genes controlling complex traits. This world-leading resource will improve knowledge of diseases like diabetes and neurological diseases.
Hybrid radiofrequency/optical catheter for effective atrial fibrillation ablation. This research project aims to advance engineering knowledge by applying an innovative, fibre-optics-based discrete optical coherence tomography to technology used for atrial fibrillation catheter ablation. RadioFrequency catheter-based ablation is far superior to cardiac drug therapy for atrial fibrillation patients. RadioFrequency catheters are not equipped with real-time lesion formation monitoring means, which ....Hybrid radiofrequency/optical catheter for effective atrial fibrillation ablation. This research project aims to advance engineering knowledge by applying an innovative, fibre-optics-based discrete optical coherence tomography to technology used for atrial fibrillation catheter ablation. RadioFrequency catheter-based ablation is far superior to cardiac drug therapy for atrial fibrillation patients. RadioFrequency catheters are not equipped with real-time lesion formation monitoring means, which enable the assessment of continuity-transmurality and prevent extra-cardiac complications, such as steam pops. Optical Coherece Tomography enables non-invasive, microscopic lesion formation assessment in real time during atrial fibrillation ablation procedures. The expected outcomes of this project are to develop a new hybrid fibre-optic/RadioFrequency catheter system and user-friendly driving software that will enable cardiac electrophysiologists to perform three key tasks not previously available.Read moreRead less
Targeting the undruggable: epitope mapping using Phylomers peptides to modulate activity of Transcription Factors. This project aims at expanding the pool of drug targets, by extending drug screening to protein-protein interaction networks. This project aims to assemble a novel technical platform to detect binding between proteins, using a combination of cell-free protein expression, AlphaScreen and single-molecule fluorescence. This pipeline has great potential to accelerate the exploration of ....Targeting the undruggable: epitope mapping using Phylomers peptides to modulate activity of Transcription Factors. This project aims at expanding the pool of drug targets, by extending drug screening to protein-protein interaction networks. This project aims to assemble a novel technical platform to detect binding between proteins, using a combination of cell-free protein expression, AlphaScreen and single-molecule fluorescence. This pipeline has great potential to accelerate the exploration of protein networks, and provides also a generic platform for drug screening on difficult targets. The project intends to screen Phylogica's libraries of peptides called Phylomers to discover tight binders to a Transcription Factor, Sox18. The objective of this project is to determine which Phylomers can disrupt specific interactions between Sox18 and its binding partners involved in lymphangiogenesis.Read moreRead less
A microfluidic array of phylomers for rapid discovery of peptide probes and biomarkers. This project, through an alliance with Phylogica, aims at exploiting a unique source of structural diversity for drug discovery, harvesting the creativity of nature in its most exotic places. The project will develop a novel approach to validate design and validate drug candidates, by gathering them on a single screening chip for a powerful discovery platform.
Imaging Mass Spectrometry (IMS), a peptide biomarker discovery tool using tissue. Cancer is the second most common cause of death in Australia. The newly developed technology of Imaging Mass Spectrometry for peptides in tissue has the potential to discover biomarkers for early diagnosis of cancer. This new technology could avoid a number of cancer deaths and reduce suffering of patients through earlier and better diagnosis.