Therapeutic Implications Of A Molecular Link Between Survivin And Telomerase Reverse Transcriptase
Funder
National Health and Medical Research Council
Funding Amount
$547,970.00
Summary
A unifying feature of all types of cancer cells is that they are immortal. Our investigations will build upon our recent results that showed the gene survivin is involved in cancer cell immortalisation. We will characterise a molecular link between survivin and the enzyme telomerase, which is central to cancer cell immortality. Furthermore, we will demonstrate the therapeutic potential of turning off both survivin and telomerase as a novel approach to halting the growth of cancer cells.
MOLECULAR CELL BIOLOGICAL ANALYSIS OF CAVEOLIN SECRETION
Funder
National Health and Medical Research Council
Funding Amount
$536,657.00
Summary
Aggressive forms of prostate cancer are associated with the release of a protein, called caveolin, from the cancerous cells. Caveolin is normally embedded in the cell surface and drives the formation of microscopic pits termed caveolae. In this proposal we will investigate how caveolin is secreted with a long-term goal of preventing the secretion, or the action, of caveolin.
Heterogeneous Nuclear Ribonucleoprotein Role In Alternative RNA Splicing And Human Disease
Funder
National Health and Medical Research Council
Funding Amount
$254,250.00
Summary
Control of the use of DNA, gene expression, is vital to all living organisms, especially in development and disease. The information in the genes of DNA is transferred to an intermediate molecule, mRNA, in a process called transcription. The genetic information in the mRNA is subsequently used, in the process called translation, to make the protein encoded by the original gene. The switching on and off of DNA appears to be most frequently controlled at the transcription step but recently it has ....Control of the use of DNA, gene expression, is vital to all living organisms, especially in development and disease. The information in the genes of DNA is transferred to an intermediate molecule, mRNA, in a process called transcription. The genetic information in the mRNA is subsequently used, in the process called translation, to make the protein encoded by the original gene. The switching on and off of DNA appears to be most frequently controlled at the transcription step but recently it has become apparent that there are many post-transcriptional events that govern how efficiently the genetic information is ultimately converted to protein molecules. An important step is the cutting out of parts (introns) of the RNA molecule that is copied from DNA, and splicing of the retained sections (exons). During this process the RNA may also lose one or more of its exons. As a result of this variable retention of exons a single gene may produce many isoforms of the protein it encodes. By this mechanism the roughly 30,000 genes in the human genome can give rise to potentially hundreds of thousands of proteins. RNA splicing connects to cancer in two ways. First, changes in the concentrations of the proteins that control splicing may change the isoforms, resulting in changes that lead to uncontrolled cell proliferation. Secondly, DNA mutations that affect the splicing process can also vary the ratios of the isoforms produced from a gene: if this occurs in a protein that is involved in the growth of cells this too may lead to cancer. In this project we will study the molecular mechanism of this alternative splicing, and particularly a group of proteins that generally favour the excision of some exons, with a focus on cancer cells. Recent publications have highlighted the potential for the therapeutic use of drugs that target the splicing apparatus: it is anticipated that studies of alternative splicing will underpin development of new therapeutic agents.Read moreRead less
The Role Of A Phosphorylated Ser/Tyr Bidentate Motif In Leukemia And Myeloproliferative Disorders
Funder
National Health and Medical Research Council
Funding Amount
$279,254.00
Summary
The ability of a normal cell to survive and grow is subject to tight control. Cancer cells escape both these controls and survive and grow in an deregulated manner. Many therapies that are in clinical use or in pre-clinical development target the growth of cancer cells. While such an approach has the advantage of being highly effective in stopping the advance of cancer cell growth, it may allow the long-term survival of some cancer cells and increase the possibility that these cells will become ....The ability of a normal cell to survive and grow is subject to tight control. Cancer cells escape both these controls and survive and grow in an deregulated manner. Many therapies that are in clinical use or in pre-clinical development target the growth of cancer cells. While such an approach has the advantage of being highly effective in stopping the advance of cancer cell growth, it may allow the long-term survival of some cancer cells and increase the possibility that these cells will become resistant to drug treatment leading to disease relapse. On the other hand, therapies that target the survival of malignant cells would be expected to pull the rug from underneath cancer by killing the malignant cells regardless of whether they are growing or not. We have identified a signalling device in normal blood cells that controls both the growth and survival of cells. This device is in effect a switch with 2 components both of which are normally turned on and off. These 2 components are differentially wired to to the cell transmitting unique signals. Importantly, we have found that this switch is faulty in blood cancers and is permanently on in some leukemias promoting their prolonged life-span. Targetting specific components of this unregulated switch may provide new and improved approaches for the development of therapeutics in the treatment of leukemia.Read moreRead less
Conantokin selectivity for heteromeric N-methyl-D-aspartate (NMDA) receptors. NMDA receptors are ligand gated ion channels formed by heterogeneous population of subunits with distinct pharmacological and biophysical properties. The heterogeneic receptors are differentially expressed during development and play an important role in many physiological and pathological processes. Conantokins are toxins isolated from Conus venoms, which target NMDA receptor subunits with high affinity. The primary g ....Conantokin selectivity for heteromeric N-methyl-D-aspartate (NMDA) receptors. NMDA receptors are ligand gated ion channels formed by heterogeneous population of subunits with distinct pharmacological and biophysical properties. The heterogeneic receptors are differentially expressed during development and play an important role in many physiological and pathological processes. Conantokins are toxins isolated from Conus venoms, which target NMDA receptor subunits with high affinity. The primary goal of this study is to examine the effects of conantokins on the molecular properties of different NMDA receptor subtypes in vivo and in vitro.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0989861
Funder
Australian Research Council
Funding Amount
$650,000.00
Summary
Electron Microscopes for Nanometer-Scale Imaging/Microanalysis in the Materials, Biological, Physical, Engineering and Chemical Sciences. Electron microscopes have contributed to many of the most significant discoveries and technological advances of the last 6 decades. High resolution transmission and scanning electron microscopes have become essential research infrastructure in internationally competitive materials science, biology, bio-medical science, physics, chemistry and a broad range of e ....Electron Microscopes for Nanometer-Scale Imaging/Microanalysis in the Materials, Biological, Physical, Engineering and Chemical Sciences. Electron microscopes have contributed to many of the most significant discoveries and technological advances of the last 6 decades. High resolution transmission and scanning electron microscopes have become essential research infrastructure in internationally competitive materials science, biology, bio-medical science, physics, chemistry and a broad range of engineering disciplines. This capability is not currently available in the Newcastle, Hunter, Central and Lower North Coast and New England regions. This proposal is aimed at satisfying the considerable demand for high resolution microscopy in these areas leading to high quality research outcomes across 3 National Research Priorities and a strong contribution to research training.Read moreRead less
Dissection of nodule and lateral root development in the model legume Lotus japonicus. We propose to isolate and decipher the function of plant genes involved in nodule development, with the view to extend and compare this knowledge to lateral root formation. While nodulation and lateral root formation are distinct processes, they appear to share anatomical and biochemical features. Working hypothesis is that nodule formation borrowed functions from lateral root development. Our approach impleme ....Dissection of nodule and lateral root development in the model legume Lotus japonicus. We propose to isolate and decipher the function of plant genes involved in nodule development, with the view to extend and compare this knowledge to lateral root formation. While nodulation and lateral root formation are distinct processes, they appear to share anatomical and biochemical features. Working hypothesis is that nodule formation borrowed functions from lateral root development. Our approach implements T-DNA and transposon insertional mutagenesis in the model legume Lotus japonicus. The success of this project will contribute significantly to the studies of plant-microbe interaction and plant morphogenesis.Read moreRead less
Development of novel high efficiency thermoelectric oxides for high temperature power generation. Thermoelectric materials are considered as a key factor in clean energy production, based on the conversion of waste heat emitted by power plants and automobiles to electricity. A series of novel high performance Co-based oxide thermoelectric materials will be developed by this project using nanotechnology and advanced material processing techniques. Significant improvement of the heat-to-electricit ....Development of novel high efficiency thermoelectric oxides for high temperature power generation. Thermoelectric materials are considered as a key factor in clean energy production, based on the conversion of waste heat emitted by power plants and automobiles to electricity. A series of novel high performance Co-based oxide thermoelectric materials will be developed by this project using nanotechnology and advanced material processing techniques. Significant improvement of the heat-to-electricity conversion factor is expected to result from the proposed program. The novel thermoelectric oxides with high thermoelectric performance will be practically used for high temperature power generation. This will provide a long-term solution to the global warming threat through decreasing amounts of waste heat presently generated. Read moreRead less
Understanding The Role Of RAS Mutations In Thyroid Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$463,854.00
Summary
My fellowship will examine the association of RAS mutations in thyroid cancer. RAS proteins are the most mutated in cancer and I will investigate how they work in thyroid cancer. RAS mutated thyroid cancer is more likely to cause death. This grant will be based in the pioneering lab of Prof Fagin at Memorial Sloan Kettering Cancer Center and the Garvan Institute of Medical Research. It is hoped by understanding these mutations, new treatments for thyroid cancer can be developed.