Targeting mitochondria with mitocans to treat cancer: mechanistic aspects. Mitochondria are the power-house of the cell and also the reservoir of proteins causing the demise of cancer cells, therefore suppressing tumour progression. This project proposes a novel way to modify certain compounds, increasing their level in mitochondria in order to maximise their anti-cancer effect.
Pharmacology Of Potential Anti-Tumour Agents: Iron Chelators Of The BpT Class
Funder
National Health and Medical Research Council
Funding Amount
$585,455.00
Summary
Pharmacology of Potential Anti-Tumour Agents: Iron Chelators of the BpT Class Cancer cells have a high iron requirement for DNA synthesis and many clinical trials showed Fe chelators are effective anti-cancer drugs. Their potential to act as anti-tumour agents has been confirmed by the entrance of Triapine into widespread NCI clinical trials. In this NHMRC Renewal, we will perform pharmacological and preclinical studies to promote the development of BpT chelators as novel anti-tumour agents.
E-Cadherin Endocytosis In Morphogenesis: Recycling And Growth Factor Induced Uptake.
Funder
National Health and Medical Research Council
Funding Amount
$498,088.00
Summary
E-cadherin is a cell-cell adhesion protein expressed in all epithelia with essential roles in establishing cell polarity and in tissue patterning during development. In the adult, E-cadherin functions to maintain epithelial integrity. E-cadherin is also a vital tumour suppressor, protecting cells against metastatic transformation. Our earlier studies showed that E-cadherin is constantly moved, or trafficked, to and from the surface of epithelial cells. The endocytosis or internalisation of cell ....E-cadherin is a cell-cell adhesion protein expressed in all epithelia with essential roles in establishing cell polarity and in tissue patterning during development. In the adult, E-cadherin functions to maintain epithelial integrity. E-cadherin is also a vital tumour suppressor, protecting cells against metastatic transformation. Our earlier studies showed that E-cadherin is constantly moved, or trafficked, to and from the surface of epithelial cells. The endocytosis or internalisation of cell surface E-cadherin serves to regulate its role in adhesion. More recently, we and others have shown that E-cadherin is endocytosed in response to growth factors, in conjunction with the activated growth factor receptors themselves. E-cadherin can influence the trafficking and signaling of these receptor tyrosine kinases. This joint endocytosis is an elegant mechanism for the simultaneous downregulation of cell adhesion and activation of signaling for cell growth and motility. The growth and differentiation of epithelial cells during tissue patterning or morphogenesis relies critically on these endocytic pathways. Our research is aimed at defining the endosomes and cellular machinery involved in E-cadherin-receptor endocytosis, moreover we will pursue initial findings suggesting that there are different pathways and fates for E-cadherin endocytosed at the behest of different growth factors. We will study endocytosis during the processes of epithelial cyst formation and tubulation of cysts as an in vitro model for mammalian morphogenesis. These studies will provide important and novel information for understanding the roles of E-cadherin in adhesion and in growth factor signaling during epithelial morphogenesis. Ultimately these findings will be of relevance to epithelial development and the prevention of cancer.Read moreRead less
Intelligent Image Processing Techniques for Novel Biomarker Discovery. This project will make an impact on Australia's international research profile by seeking a solution to a worldwide challenging problem in biomarker discovery for the detection of diseases at an early stage which requires the incorporation of the skills and knowledge from biology, medicine, engineering, computer science, and information technology. The successful outcomes of this research will make an impact on Australia's e ....Intelligent Image Processing Techniques for Novel Biomarker Discovery. This project will make an impact on Australia's international research profile by seeking a solution to a worldwide challenging problem in biomarker discovery for the detection of diseases at an early stage which requires the incorporation of the skills and knowledge from biology, medicine, engineering, computer science, and information technology. The successful outcomes of this research will make an impact on Australia's engagement in using advanced image analysis and intelligent methods for the emerging research and development of targeted drug discovery. Read moreRead less
An Automated Bioimaging System for High-Content Cell-Cycle Screening. 1) Providing a better understanding of the biological complexities
that will advance knowledge in life science research and facilitate the development of new anti-cancer drugs.
2) Supporting Australian academic institutions in a challenging field of innovative research through international, interdisciplinary collaborations, and publications in journals of high quality scientific research.
3) Providing research training ....An Automated Bioimaging System for High-Content Cell-Cycle Screening. 1) Providing a better understanding of the biological complexities
that will advance knowledge in life science research and facilitate the development of new anti-cancer drugs.
2) Supporting Australian academic institutions in a challenging field of innovative research through international, interdisciplinary collaborations, and publications in journals of high quality scientific research.
3) Providing research training in a research venture that requires expertise and collaboration in the disciplines of biology, engineering, computer science, and mathematics.
4) Bringing economic and social benefits for Australia by enhancing important industries and existing technologies in medicine, and biotechnology.
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A Randomised Controlled Trial Of Interventional Versus Conservative Treatment Of Primary Spontaneous Pneumothorax
Funder
National Health and Medical Research Council
Funding Amount
$412,315.00
Summary
Primary spontaneous pneumothorax (PSP) is a collapsed lung that occurs in otherwise healthy people without underlying lung disease. Current standard treatment is to insert a chest drain into the chest to remove the air around the collapsed lung so that the lung re-inflates rapidly ("interventional treatment"). We will determine whether doing nothing, i.e. letting the lung re-inflate slowly on its own over several weeks ("conservative treatment"), is just as good or even better for patients.
DEEP LEARNING AND PHYSIOLOGY BASED APPROACH TO DERIVE AND LINK OBSTRUCTIVE SLEEP APNOEA PHENOTYPES AND SYMPTOMATOLOGY
Funder
National Health and Medical Research Council
Funding Amount
$402,978.00
Summary
Obstructive sleep apnoea (OSA) is a highly prevalent nocturnal breathing disorder strongly related to daytime sleepiness, accident risk and reduced quality of life. However, the current severity index, the apnoea-hypopnoea index, poorly predicts daytime sleepiness and vigilance. In this project we elegantly combine physiological insight and artificial intelligence to develop and evaluate novel clinically applicable computational tools for detailed quantification of OSA severity and its symptoms.
On-line and Incremental EM-based Neural Networks: Application to Hospital Utlilization and Gene Expression Data. Artificial neural networks have been widely applied as universal classifiers in many fields, such as biomedicine. However, misunderstanding of fundamental statistical principles, which can cause misleading findings, has been frequently observed in the literature. This project aims to integrate statistical methodologies in neural networks to provide a unified approach to improve its ....On-line and Incremental EM-based Neural Networks: Application to Hospital Utlilization and Gene Expression Data. Artificial neural networks have been widely applied as universal classifiers in many fields, such as biomedicine. However, misunderstanding of fundamental statistical principles, which can cause misleading findings, has been frequently observed in the literature. This project aims to integrate statistical methodologies in neural networks to provide a unified approach to improve its applicability and efficiency in implementation. The system developed from this proposed cross-disciplinary research will be applied to hospital utilization data (hospital morbidity database, Western Australia) and gene expression data (DNA microarrays databases, Harvard University). This collaborative research will advance the international standard of Australian research communities.
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Improving Sexual Health In Men With Prostate Cancer: Randomised Controlled Trial Of Exercise And Psychosexual Therapies
Funder
National Health and Medical Research Council
Funding Amount
$583,416.00
Summary
Sexual dysfunction is one of the most common and distressing side effects of prostate cancer. Despite being a critical survivorship care issue, there is a clear gap in knowledge surrounding the optimal treatment of sexual dysfunction in men with prostate cancer. This project examines whether exercise aids in the management of sexual dysfunction and explores if an integrated treatment model incorporating pharmacological, exercise and psychosexual therapies maximises improvement in sexual health.
Inhibition Of IFN-?/? By Human Metapneumovirus And The Induction Of Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$605,251.00
Summary
The newly isolated human metapneumovirus (hMPV) causes significant respiratory illness in infants, young children and the elderly. The virus can persist long-term and may predispose individuals to chronic lung disease. This proposal aims to determine the mechanisms by which hMPV infection causes respiratory disease, with a view to improving treatments and preventing disease.