The Use Of Gene-Silencing Nanodrugs To Inhibit Lung Cancer Growth
Funder
National Health and Medical Research Council
Funding Amount
$452,950.00
Summary
Lung cancer accounts for the most cancer deaths worldwide. This research proposal will use state-of-the-art nanomedicines designed to penetrate lung tumours and suppress a gene which drives cancer growth and resistance to chemotherapy drugs. Our results could underpin new approaches that revolutionise more effective and less toxic treatments for a highly lethal malignancy.
Exploring the gene regulation networks governing mitochondrial biogenesis in Arabidopsis. Mitochondria, subcellular organelles that perform many functions indispensable to plant growth and productivity, are dynamic compartments whose protein complement changes dramatically during plant development and under stress. Yet, the cellular processes that regulate the production of these organelles are virtually unknown. By combining conventional approaches with an extremely powerful holistic method for ....Exploring the gene regulation networks governing mitochondrial biogenesis in Arabidopsis. Mitochondria, subcellular organelles that perform many functions indispensable to plant growth and productivity, are dynamic compartments whose protein complement changes dramatically during plant development and under stress. Yet, the cellular processes that regulate the production of these organelles are virtually unknown. By combining conventional approaches with an extremely powerful holistic method for simultaneously examining the expression patterns of every gene in the model plant Arabidopsis, this project will identify proteins that regulate mitochondrial biosynthesis and uncover the gene networks that these proteins control. The project outcomes will provide new opportunities for the rational manipulation of plant growth and productivity.Read moreRead less
Redirecting T-cells For Immunotherapy Of Leukaemia And Lymphoma By The Expression Of A CD19-specific Chimeric Antigen Receptor Using The PiggyBac Transposon Gene Modification System
Funder
National Health and Medical Research Council
Funding Amount
$374,876.00
Summary
Most lymphomas respond to therapy but then relapse. Immune cells can attack and kill virus related lymphomas. However, most lymphomas are NOT virus related. We will create immune cells targeting these virus negative lymphomas by inserting artificial receptors into the immune cells. These receptors attach to the lymphoma and activate the immune cells. The immune cells will home to the lymphoma, kill lymphoma cells and persist in the body for many years, preventing lymphoma relapse.
Identification of functionally important autophosphorylation site(s) on ataxia telangiectasia and Rad 3 - related (ATR) protein kinase. The integrity of our genetic material must be maintained so that it can be passed on from one generation to the next and also to minimize the risk of cancer and other pathologies in an individual. There are multiple proteins involved in protecting our DNA including several enzymes that detect and signal DNA damage to a series of pathways involved in halting the ....Identification of functionally important autophosphorylation site(s) on ataxia telangiectasia and Rad 3 - related (ATR) protein kinase. The integrity of our genetic material must be maintained so that it can be passed on from one generation to the next and also to minimize the risk of cancer and other pathologies in an individual. There are multiple proteins involved in protecting our DNA including several enzymes that detect and signal DNA damage to a series of pathways involved in halting the passage of cells through the cell cycle so that repair can occur. This project studies the mechanism of action of one of these enzymes which will be of benefit in designing new compounds to fight disease. Read moreRead less
The MYB gene as a model for global transcriptional regulation: stopping, starting and looping. This project will study how transcriptional elongation controls the MYB gene, a key regulator of normal and cancerous growth and regulation. There are three major benefits that are likely to flow from the proposed research It will strengthen research in new and important areas of transcriptional regulation, by building research capacity in Australia in the area of gene expression, particularly with res ....The MYB gene as a model for global transcriptional regulation: stopping, starting and looping. This project will study how transcriptional elongation controls the MYB gene, a key regulator of normal and cancerous growth and regulation. There are three major benefits that are likely to flow from the proposed research It will strengthen research in new and important areas of transcriptional regulation, by building research capacity in Australia in the area of gene expression, particularly with respect to transcriptional elongation and long-range regulation. It will highlight a new approach to the therapeutic targeting of MYB in cancer: data generated from this research may enable us to target MYB expression in a range of cancers including breast cancer by inhibiting transcriptional elongation. And it will provide training in advanced molecular biology to postdoctoral scientists and students.Read moreRead less
PKC-zeta-dependent Sp1 Phosphorylation: Regulatory Insights using Novel Phospho-Specific Sp1 Antibodies and Peptide Decoys. This project will demonstrate the value of novel phospho-specific Sp1 antibodies and phospho-Sp1 peptide decoys as new molecular tools to provide invaluable insights into the regulatory roles of phosphorylated Sp1 in the control of gene expression, an area poorly defined at the present time. These agents will be used to increase our fundamental understanding of Sp1 activity ....PKC-zeta-dependent Sp1 Phosphorylation: Regulatory Insights using Novel Phospho-Specific Sp1 Antibodies and Peptide Decoys. This project will demonstrate the value of novel phospho-specific Sp1 antibodies and phospho-Sp1 peptide decoys as new molecular tools to provide invaluable insights into the regulatory roles of phosphorylated Sp1 in the control of gene expression, an area poorly defined at the present time. These agents will be used to increase our fundamental understanding of Sp1 activity by identifying physiologic agonists of the PKC-zeta-phospho-Sp1 axis and FasL-dependent apoptosis, interactions of phospho-Sp1 with the authentic FasL promoter and its recruitment of collaborative factors. The commercial exploitation of phospho-specific Sp1 antibodies and phospho-Sp1 peptide decoys will generate economic returns to Australia.Read moreRead less
Exploration of a mechanistic link between eukaryotic transcription and translation. Gene transcription is functionally coupled to other aspects of eukaryotic mRNA metabolism, emphasizing a need for integrated approaches to analyse the gene expression pathway. We have shown in previous work that yeast cells, when responding to external stimuli, show a tight correlation between changes in the transcriptome composition and homodirectional alterations in the translation state of mRNAs. This phenomen ....Exploration of a mechanistic link between eukaryotic transcription and translation. Gene transcription is functionally coupled to other aspects of eukaryotic mRNA metabolism, emphasizing a need for integrated approaches to analyse the gene expression pathway. We have shown in previous work that yeast cells, when responding to external stimuli, show a tight correlation between changes in the transcriptome composition and homodirectional alterations in the translation state of mRNAs. This phenomenon of ?potentiation? may serve to amplify signal-induced changes in the transcriptome at the translational level. This project will begin to unravel the molecular mechanisms underlying potentiation using experiments designed to distinguish between transcription- and translation-driven mechanisms.Read moreRead less
PKC-zeta-dependent Sp1 phosphorylation: Identification of phosphorylated amino acids, demonstration of functional significance, generation and use of novel phospho-specific Sp1 antibodies. Sp1 is a widely expressed transcription factor that controls the basal expression of virtually every mammalian gene, including that of PDGF-B. We recently reported that PDGF-B expression atypical protein kinase C-zeta phosphorylation of Sp1. Building on these seminal findings, this project will first, delinea ....PKC-zeta-dependent Sp1 phosphorylation: Identification of phosphorylated amino acids, demonstration of functional significance, generation and use of novel phospho-specific Sp1 antibodies. Sp1 is a widely expressed transcription factor that controls the basal expression of virtually every mammalian gene, including that of PDGF-B. We recently reported that PDGF-B expression atypical protein kinase C-zeta phosphorylation of Sp1. Building on these seminal findings, this project will first, delineate the specific amino acid residues in the zinc finger region of Sp1 phosphorylated by PKC-zeta; second, demonstrate the functional importance of these site-specific modifications in the PKC-zeta-Sp1-PDGF-B system and the expression of other genes, and third, generate and use novel antibodies uniquely recognising phosphorylated Sp1 as molecular and diagnostic agents.Read moreRead less
Molecular mechanisms of stem cell self-renewal. Muscle growth and regeneration is critically dependent on its stem cell compartment. We have discovered that the p38 MAPK pathway is essential for stem cell self-renewal in the C2C12 myogenic cell line. This proposal seeks to understand the molecular basis of stem cell self-renewal in skeletal muscles, data that may be applicable to many stem cell systems, and to the enormous promise of stem cell therapies for injury and diseases of the aged. We wi ....Molecular mechanisms of stem cell self-renewal. Muscle growth and regeneration is critically dependent on its stem cell compartment. We have discovered that the p38 MAPK pathway is essential for stem cell self-renewal in the C2C12 myogenic cell line. This proposal seeks to understand the molecular basis of stem cell self-renewal in skeletal muscles, data that may be applicable to many stem cell systems, and to the enormous promise of stem cell therapies for injury and diseases of the aged. We will attempt to alter the balance of stem cell production by enforced p38 expression, and take microarray and proteomics approaches to define stem cell pathways.Read moreRead less
How Do Bone-active Drugs Increase Patient Survival?
Funder
National Health and Medical Research Council
Funding Amount
$613,952.00
Summary
Bisphosphonates are a class of drugs used to prevent bone destruction in diseases such as osteoporosis. Evidence is emerging that these drugs also act on cells outside the skeleton to have additional beneficial effects, for example prolonging patient survival. This project will identify the cells affected and the mechanisms involved. With this knowledge, these drugs could be used more effectively and in different ways for the prevention or treatment of cancer and chronic human illnesses.