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
Genome Approaches to Investigate Metabolic Coordination in Plant Cells. Metabolism of C and N in legume nodules requires interaction between the symbiotic bacteria and plant organelles, particularly metabolism in plastids and mitochondria. Fixed N is assimilated through the de novo synthesis of purines in both plastids and mitochondria. However, each of the nine pathway enzymes is encoded by a single gene, indicating each protein is targeted to both organelles. Purine metabolism will provide ....Genome Approaches to Investigate Metabolic Coordination in Plant Cells. Metabolism of C and N in legume nodules requires interaction between the symbiotic bacteria and plant organelles, particularly metabolism in plastids and mitochondria. Fixed N is assimilated through the de novo synthesis of purines in both plastids and mitochondria. However, each of the nine pathway enzymes is encoded by a single gene, indicating each protein is targeted to both organelles. Purine metabolism will provide a model to assess the more general occurrence of dual-targeted proteins in plants. The aim is to identify and eventually exploit the signalling mechanism(s) that mediate communication between plastids and mitochondria.Read moreRead less
The control of elongation factor 2 and its role in the regulation of protein synthesis. Protein synthesis is a key process in living cells. The main stage, elongation, is regulated through phosphorylation of elongation factor eEF2 in response to hormones, amino acids and cellular energy status, via changes in the activity of eEF2 kinase. We will study how these conditions control eEF2 kinase by studying its phosphorylation and identifying new kinases that regulate it. We will explore the role of ....The control of elongation factor 2 and its role in the regulation of protein synthesis. Protein synthesis is a key process in living cells. The main stage, elongation, is regulated through phosphorylation of elongation factor eEF2 in response to hormones, amino acids and cellular energy status, via changes in the activity of eEF2 kinase. We will study how these conditions control eEF2 kinase by studying its phosphorylation and identifying new kinases that regulate it. We will explore the role of eEF2 in controlling protein synthesis, seek new substrates for eEF2 kinase and initiate work to elucidate the structure of this unusual enzyme. This will enhance, in a range of ways, fundamental understanding of cell physiology.Read moreRead less
Dynamics and assembly of BRCA1-associated DNA repair complexes. This research project will study how cells respond to breakages in DNA by directing a team of repair proteins to the damaged DNA. BRCA1 is one of several repair proteins, and BRCA1 gene mutations impair its DNA repair function and predispose patients to breast/ovarian cancer. Improved insight into BRCA1 regulation could enhance our understanding of this disease. There are >13,000 new cases of breast/ovarian cancer each year with mor ....Dynamics and assembly of BRCA1-associated DNA repair complexes. This research project will study how cells respond to breakages in DNA by directing a team of repair proteins to the damaged DNA. BRCA1 is one of several repair proteins, and BRCA1 gene mutations impair its DNA repair function and predispose patients to breast/ovarian cancer. Improved insight into BRCA1 regulation could enhance our understanding of this disease. There are >13,000 new cases of breast/ovarian cancer each year with more than 3,300 deaths, making it a serious healthcare issue in Australia, and placing this project within Research Priority 2: Promoting and Maintaining Good Health. If successful this project will yield insights into the role of BRCA1 in fixing DNA aberrations which could help in anti-cancer agent development. Read moreRead less
Mitochondrial targeting of the DNA repair protein BARD1. This is a fundamental research project to address a novel localisation pattern of the nuclear DNA repair protein, BARD1. BARD1 gene mutations occur in a subset of breast/ovarian cancer patients, and improved insight into BARD1 regulation could enhance our understanding of this disease. There are over 13,000 new cases of breast/ovarian cancer each year with more than 3,300 deaths, making it a serious healthcare issue in Australia, and placi ....Mitochondrial targeting of the DNA repair protein BARD1. This is a fundamental research project to address a novel localisation pattern of the nuclear DNA repair protein, BARD1. BARD1 gene mutations occur in a subset of breast/ovarian cancer patients, and improved insight into BARD1 regulation could enhance our understanding of this disease. There are over 13,000 new cases of breast/ovarian cancer each year with more than 3,300 deaths, making it a serious healthcare issue in Australia, and placing this project within Research Priority 2: Promoting and Maintaining Good Health. If successful this project will characterise the cellular transport route of BARD1 which could help in anti-cancer agent development. Read moreRead less
Investigations of signals involved in redox-regulation of carbon storage. This project seeks molecular understanding of signals optimising storage processes in plants in response to nutrient supply and environmental stress. Discovering regulatory signals that control carbon storage and yield will maintain Australia's international reputation in this field of research and may provide technical opportunities to improve crops in healthy or stressful environments. This is an issue of increasing impo ....Investigations of signals involved in redox-regulation of carbon storage. This project seeks molecular understanding of signals optimising storage processes in plants in response to nutrient supply and environmental stress. Discovering regulatory signals that control carbon storage and yield will maintain Australia's international reputation in this field of research and may provide technical opportunities to improve crops in healthy or stressful environments. This is an issue of increasing importance especially in the context of global warming. Read moreRead less
Is transport of miRNAs essential for plant development? This project will provide knowledge of how a new class of biologically active molecule (micro RNA) regulates expression of genes at sites in the plant that are critical for growth and development. MicroRNAs are believed to influence the size and shape of plants, how rapidly they grow and how well they produce and fill seeds. These molecules are part of a group of bioactive signals that move throughout the plant, functioning like hormones bu ....Is transport of miRNAs essential for plant development? This project will provide knowledge of how a new class of biologically active molecule (micro RNA) regulates expression of genes at sites in the plant that are critical for growth and development. MicroRNAs are believed to influence the size and shape of plants, how rapidly they grow and how well they produce and fill seeds. These molecules are part of a group of bioactive signals that move throughout the plant, functioning like hormones but directly influencing how well critical genes work. Their exploitation holds great promise for manipulating plant performance and enhancing crop yields. Read moreRead less
Integration of Cellular Gene Regulation Processes. This research program aims to identify specific transcriptional regulatory networks in yeast, to determine how some of these networks interact with each other and within these networks to identify the roles of genes whose functions are currently unknown. It will identify systems regulating genes concerned with one-carbon metabolism, cellular responses to oxidative stress and developmental changes associated with meiosis. It will provide a fra ....Integration of Cellular Gene Regulation Processes. This research program aims to identify specific transcriptional regulatory networks in yeast, to determine how some of these networks interact with each other and within these networks to identify the roles of genes whose functions are currently unknown. It will identify systems regulating genes concerned with one-carbon metabolism, cellular responses to oxidative stress and developmental changes associated with meiosis. It will provide a framework to test regulatory network models and to analyse the molecular basis of interactions between control systems. This research will eventually provide the ability to predict how cells respond to drugs and other environmental stimuli.Read moreRead less
Nanoprobe and Microprobe Spectroscopic Techniques in Drug Design, Probing Mechanisms of Diseases, and Bioinorganic Chemistry. Nanoprobe and microprobe spectroscopic techniques offer unparalleled opportunities to probe the structures and distributions of drugs, carcinogens, and biomolecules in cultured cells and tissues. Such techniques represent new frontiers in understanding in vivo metabolic processes at the molecular level, as well as providing unprecedented information on the metabolism and ....Nanoprobe and Microprobe Spectroscopic Techniques in Drug Design, Probing Mechanisms of Diseases, and Bioinorganic Chemistry. Nanoprobe and microprobe spectroscopic techniques offer unparalleled opportunities to probe the structures and distributions of drugs, carcinogens, and biomolecules in cultured cells and tissues. Such techniques represent new frontiers in understanding in vivo metabolic processes at the molecular level, as well as providing unprecedented information on the metabolism and distributions of pharmaceuticals and toxins involved in the treatment and cause of diseases, such as cancer. This project is aimed at pushing the boundaries of nanoprobe and microprobe (X-ray absorption, SRIXE, PIXE, Raman and two-photon fluorescence) techniques for such applications.Read moreRead less
Chemical and Biochemical Characterisation of Novel Iron Chelators with Therapeutic Potential. Iron is essential for life, but iron-overload is a potentially fatal condition. There is no natural mechanism to excrete iron in humans, so patients suffering from iron-overload disorders are treated with the chelator Desferal to enable iron excretion typically from an early age. Desferal is orally ineffective and must be given by subcutaneous infusion (12-24h, 5-6 days/week) resulting in poor patient c ....Chemical and Biochemical Characterisation of Novel Iron Chelators with Therapeutic Potential. Iron is essential for life, but iron-overload is a potentially fatal condition. There is no natural mechanism to excrete iron in humans, so patients suffering from iron-overload disorders are treated with the chelator Desferal to enable iron excretion typically from an early age. Desferal is orally ineffective and must be given by subcutaneous infusion (12-24h, 5-6 days/week) resulting in poor patient compliance. We will conduct critical chemical and biological experiments with a new series of potentially orally active iron chelators identified in our lab. The results from this project will be vital for the development of these compounds as pharmaceuticals.Read moreRead less