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
Cellular signals controlling oocyte activation. This research will significantly advance our understanding of the basic biological processes that underpin the fertility rate of all mammals and are key to the immediate and future health and well-being of Australian landscape and society. Understanding the processes that maintain healthy quiescent oocytes over many years before activation and subsequent growth will enable development of methods of increasing productivity in domestic animals and en ....Cellular signals controlling oocyte activation. This research will significantly advance our understanding of the basic biological processes that underpin the fertility rate of all mammals and are key to the immediate and future health and well-being of Australian landscape and society. Understanding the processes that maintain healthy quiescent oocytes over many years before activation and subsequent growth will enable development of methods of increasing productivity in domestic animals and enhancing fertility in endangered species. Knowledge of these cellular mechanisms will underpin biotechnology platforms necessary for novel methods of feral animal population control thus contributing at multiple levels to an economically sustainable Australia.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0668479
Funder
Australian Research Council
Funding Amount
$265,000.00
Summary
Advanced Imaging Flow Cytometry Facility for NSW. The scientific advances that will be possible with the acquisition of this novel, cutting-edge instrument will enhance the research outputs of all investigators using it. Projects where the investigation of single cells is used to elucidate the basic life processes of eukaryotic cells across all species of animals, including the investigation of both normal and abnormal function, will be immeasurably enhanced by both the qualitative and quantitat ....Advanced Imaging Flow Cytometry Facility for NSW. The scientific advances that will be possible with the acquisition of this novel, cutting-edge instrument will enhance the research outputs of all investigators using it. Projects where the investigation of single cells is used to elucidate the basic life processes of eukaryotic cells across all species of animals, including the investigation of both normal and abnormal function, will be immeasurably enhanced by both the qualitative and quantitative statistical information about these processes that is generated by this instrument. This in turn will inform new approaches to improve and maintain the health of the human and animal community.Read moreRead less
Characterisation of APC intracellular trafficking pathways. This is a fundamental research project aimed at addressing the cell biology of the APC tumour suppressor protein. APC gene mutations are directly linked to the development of colorectal cancer, a serious healthcare issue in Australia with approximately 12,400 new cases diagnosed each year and around 4,700 deaths. The severity of cases in men and women who develop colorectal cancer makes this a socio-economically serious health issue, an ....Characterisation of APC intracellular trafficking pathways. This is a fundamental research project aimed at addressing the cell biology of the APC tumour suppressor protein. APC gene mutations are directly linked to the development of colorectal cancer, a serious healthcare issue in Australia with approximately 12,400 new cases diagnosed each year and around 4,700 deaths. The severity of cases in men and women who develop colorectal cancer makes this a socio-economically serious health issue, and our project falls within the Research Priority 2: Promoting and Maintaining Good Health. If successful our project will identify localisation patterns and pathways of movement of APC within cells, which could ultimately help in development of treatments. Read moreRead less
How IGFBP-3 improves cancer cell responsiveness to DNA-damaging therapies. A protein called IGFBP-3 can modulate the way cancer cells respond to treatments such as radiotherapy and certain chemotherapy drugs. These therapies, which act by damaging cells' DNA, play an important role in the treatment of many cancers, but their effectiveness is limited by the ability of cells to oppose the treatment by repairing damaged DNA. This project aims to discover how IGFBP-3 acts to change cancer cells' res ....How IGFBP-3 improves cancer cell responsiveness to DNA-damaging therapies. A protein called IGFBP-3 can modulate the way cancer cells respond to treatments such as radiotherapy and certain chemotherapy drugs. These therapies, which act by damaging cells' DNA, play an important role in the treatment of many cancers, but their effectiveness is limited by the ability of cells to oppose the treatment by repairing damaged DNA. This project aims to discover how IGFBP-3 acts to change cancer cells' response to treatment, using breast cancer cells growing in culture as a model system. This work has the potential to lead to improvements in the treatment of cancer patients by increasing our understanding of what happens when cancer cells are exposed to radio- or chemotherapy.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0989744
Funder
Australian Research Council
Funding Amount
$500,000.00
Summary
7-laser BD LSR-II and Cellomics ArrayScan VTi, to enhance capability and throughput for the NSW Advanced Cytometry Facility. The scientific advances that will be possible with the acquisition of these complementary cutting-edge instruments will enhance the research outputs of all investigators using it. Projects where investigation of either suspended or adherent live cells is used to elucidate basic life processes of eukaryotic cells across all species of animals, including the investigation of ....7-laser BD LSR-II and Cellomics ArrayScan VTi, to enhance capability and throughput for the NSW Advanced Cytometry Facility. The scientific advances that will be possible with the acquisition of these complementary cutting-edge instruments will enhance the research outputs of all investigators using it. Projects where investigation of either suspended or adherent live cells is used to elucidate basic life processes of eukaryotic cells across all species of animals, including the investigation of both normal and abnormal function, will be immeasurably enhanced by both the qualitative and quantitative statistical information about these processes that is generated by this instrumentation. This in turn will inform new approaches to improve and maintain the health of both humans and animals.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
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
Hierarchical Phosphorylation of Tyrosine Hydroxylase is Dependent on the Activation Sequence of Signaling Pathways. Protein phosphorylation is a fundamental process in biology. It controls protein expression and function in all cells. Hierarchical phosphorylation is defined as the phosphorylation of a protein at one site leading to an altered phosphorylation at another site on the same protein and an altered biological outcome. We have discovered that the enzyme tyrosine hydroxylase undergoes a ....Hierarchical Phosphorylation of Tyrosine Hydroxylase is Dependent on the Activation Sequence of Signaling Pathways. Protein phosphorylation is a fundamental process in biology. It controls protein expression and function in all cells. Hierarchical phosphorylation is defined as the phosphorylation of a protein at one site leading to an altered phosphorylation at another site on the same protein and an altered biological outcome. We have discovered that the enzyme tyrosine hydroxylase undergoes a form of hierarchical phosphorylation not previously reported. Here we examine hierarchical phosphorylation in rat and human tyrosine hydroxylase and its functional consequence in intact cells. The approaches and methods developed will also be applicable to investigation of hierarchical phosphorylation in other proteins.Read moreRead less