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
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
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
Discovery And Mechanisms Of Host Cell Factors In HIV Uncoating
Funder
National Health and Medical Research Council
Funding Amount
$635,098.00
Summary
HIV entry into the host cell involves release of its capsid, a protein shell protecting the viral genome. The capsid hijacks host proteins to cloak itself from cellular defenses while the cell has evolved sensors that can block viral infection. This proposal aims to discover proteins involved in this arms race between host and virus and decipher how they control capsid disassembly. This insight will help design new drugs against HIV infection and new ways to deliver genes for gene therapies.
Structural And Functional Analysis Of A Cancer-linked Co-regulator Complex
Funder
National Health and Medical Research Council
Funding Amount
$729,571.00
Summary
We seek to understand the mechanisms by which genes are switched on and off throughout our lifetime. A number of multi-component protein machines are involved in this process but their make-up and mechanism of action is not understood. We will investigate the structure and function of one of these machines that has been strongly linked to cancer.
Prion-like Behaviour In Immunity: Super-sized Signalling Platforms?
Funder
National Health and Medical Research Council
Funding Amount
$611,995.00
Summary
Prions have been mostly associated with pathologies but recent discoveries show that prion-like behaviour may be beneficial, enhancing our immune response for example. To test this, we want to systematically explore all human proteins involved in the defence against pathogens, find new prion-like trends and probe their role in the innate immune response.
Steroidal control of male meiosis. This innovative project will study a complex cellular process (meiosis) essential for sperm development and sexual reproduction. Collaborations and novel experimental design provide cutting edge techniques and opportunity for Australian researchers to contribute important discoveries to this field. We aim to provide new knowledge of steroid-dependent molecular factors that may activate (or inhibit) meiosis. Such novel information may significantly impact divers ....Steroidal control of male meiosis. This innovative project will study a complex cellular process (meiosis) essential for sperm development and sexual reproduction. Collaborations and novel experimental design provide cutting edge techniques and opportunity for Australian researchers to contribute important discoveries to this field. We aim to provide new knowledge of steroid-dependent molecular factors that may activate (or inhibit) meiosis. Such novel information may significantly impact diverse areas related to controlling mammalian reproductive development, such as health and well-being (a healthy start to life, fertility control), farming and agriculture (livestock production, pest management) and the Australian environment (conservation, pest management).Read moreRead less