Identifying Resistance Mechanisms Of Targeted BRAF Inhibitors In Metastatic Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$379,015.00
Summary
Late-stage melanoma is an aggressive skin cancer for which traditional treatment strategies such as chemotherapy are ineffective. Recently, a new class of targeted drugs (BRAF inhibitors) has become the standard of care for a subset of melanoma patients; however, long term treatment success is complicated by drug resistance. This study will identify the causes of resistance with the purpose to improve targeted drug strategies and increase survival rates for late-stage melanoma patients.
Modulating Skin Regenerative Responses To Improve Wound Repair And Fight Carcinogenesis
Funder
National Health and Medical Research Council
Funding Amount
$470,144.00
Summary
Skin disorders, such as hard to heal wounds or the most common skin cancers, are a major burden on the national health system. Despite their different nature they employ similar mechanisms of response to injury. In this project we intend to develop a comprehensive understanding of the genetic and molecular mechanisms at play to allow clinical interventions to prevent or to cure these disorders.
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.
Low-energy electron transport in soft-condensed biological matter. To obtain optimal accuracy and selectivity of ionising radiation based technologies requires an understanding and quantification of the underpinning fundamental physical processes. This project will focus on developing accurate theoretical models of low-energy electron transport in biological matter which account for new physical mechanisms.
EGFR-directed radioimmunotherapy combined with chemotherapy and DNA repair inhibition: development towards clinical application for aggressive cancers. Pancreatic ductal adenocarcinoma (PDAC) and triple negative breast cancer (TNBC) are aggressive diseases which lack effective therapies in clinical use. A novel and curative therapy was developed against PDAC and TNBC which involves targeted radiotherapy combined with chemotherapy and DNA damage response inhibition. This project will develop a “p ....EGFR-directed radioimmunotherapy combined with chemotherapy and DNA repair inhibition: development towards clinical application for aggressive cancers. Pancreatic ductal adenocarcinoma (PDAC) and triple negative breast cancer (TNBC) are aggressive diseases which lack effective therapies in clinical use. A novel and curative therapy was developed against PDAC and TNBC which involves targeted radiotherapy combined with chemotherapy and DNA damage response inhibition. This project will develop a “preclinical data package” comprising a biological rationale and preclinical evidence of safety and efficacy that together would justify an early phase clinical trial. This package includes the choice of formulations, mechanism of action and safety studies. This development will have an immediate impact for PDAC and TNBC patients and a future impact on other EGFR-positive cancers.Read moreRead less
Origin of multicellularity in animals: identification and analysis of intercellular signalling pathways in a basal metazoan, the demosponge Reniera. The Reniera genome project is a multi-million dollar collaboration between JGI (US-DOE) and Australian scientists that will see the sequencing of the first Australian marine animal by 2006. This project will significantly advance our understanding of the origins of animals and contribute to the reconstruction of creatures that lived over 600 million ....Origin of multicellularity in animals: identification and analysis of intercellular signalling pathways in a basal metazoan, the demosponge Reniera. The Reniera genome project is a multi-million dollar collaboration between JGI (US-DOE) and Australian scientists that will see the sequencing of the first Australian marine animal by 2006. This project will significantly advance our understanding of the origins of animals and contribute to the reconstruction of creatures that lived over 600 million years ago. A major outcome of this reconstruction will be a fundamental understanding of how cells communicate with each other during the process of development to give rise to the diversity of cell types within multicellular animals. This study will also shed light on what happens when cell communication goes astray, as observed in a range of human malignancies, including cancer. Read moreRead less
How does timing affect mammalian brain development and evolution? This project aims to generate fundamental knowledge on the origin of diversity in mammalian brain circuits by studying development of marsupials and rodents. The expected outcome is to elucidate how differences in the timing, rate and sequence of development of gene expression, cell differentiation and circuit formation can relate to the origin of key evolutionary innovations in the mammalian brain. The significance of understandi ....How does timing affect mammalian brain development and evolution? This project aims to generate fundamental knowledge on the origin of diversity in mammalian brain circuits by studying development of marsupials and rodents. The expected outcome is to elucidate how differences in the timing, rate and sequence of development of gene expression, cell differentiation and circuit formation can relate to the origin of key evolutionary innovations in the mammalian brain. The significance of understanding the dynamics of developmental systems that shape complex brain traits includes establishing new developmental paradigms in evolutionary theory, generating new tools to investigate and manipulate brain gene expression in vivo, and the potential discovery of the causes of neurodevelopmental dysfunction.Read moreRead less
Novel collision experiments with metastable neon atoms in an atom trap. The aim of this project is to investigate collisions involving atoms in long lived excited states (metastable states). The project will utilise a magneto-optical trap to investigate electron-atom collisions as well as interatomic collisions for ultra-cold atoms. The outcomes of such investigations extend scientific knowledge of these important processes as a well as provide data for testing fundamental scattering theories. T ....Novel collision experiments with metastable neon atoms in an atom trap. The aim of this project is to investigate collisions involving atoms in long lived excited states (metastable states). The project will utilise a magneto-optical trap to investigate electron-atom collisions as well as interatomic collisions for ultra-cold atoms. The outcomes of such investigations extend scientific knowledge of these important processes as a well as provide data for testing fundamental scattering theories. This scientific knowledge may lead to further technological advances such as more efficient light sources or a metastable-atom laser that could be used for the production of nano-scale electric circuits.Read moreRead less
Dynamics and correlations of many-body systems. The proposed program will greatly enhance Australian science through linking innovative
theoretical techniques with the successful ongoing Australian experimental program in atom
lasers, atom chip interferometry and ultra-cold fermions. Pioneering theoretical methods in
quantum phase-space are internationally recognized, and will be extended into new areas relevant
to Australia. These have fundamental significance to fields ranging from nanotec ....Dynamics and correlations of many-body systems. The proposed program will greatly enhance Australian science through linking innovative
theoretical techniques with the successful ongoing Australian experimental program in atom
lasers, atom chip interferometry and ultra-cold fermions. Pioneering theoretical methods in
quantum phase-space are internationally recognized, and will be extended into new areas relevant
to Australia. These have fundamental significance to fields ranging from nanotechnology to
astrophysics, as well as providing a route to improved atomic clocks and other instruments.
Combining these theoretical and computational methods from the physical sciences with biology
and genetics will provide future cross-disciplinary benefits to Australian biomedical science.Read moreRead less
Physiologically-based Pharmacokinetics And Pharmacodynamics Of Therapeutic Stem Cells For Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$848,710.00
Summary
This project focuses on the challenging area of effective and optimal dosing cell-based therapy for liver diseases. We will investigate the fate and therapeutic effects of natural, modified and artificial therapeutic cells in the body and in liver regions using a physiologically-based kinetic model. Our key goal is advance cell therapy by providing a better understanding and dosing guidelines.