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 role of neutral amino acid transport in normal physiology. Future benefits of these studies include the Promotion and Maintenance of Good Health achieved by providing: (1) a better understanding of brain and balance disorders; (2) insights into the damaging effects of the sun and; (3) existing neonatal screening programmes for Hartnup disorder with greater scientific foundation regarding the implications of inheriting this condition, including dietary advce. We will be able to provide Austr ....The role of neutral amino acid transport in normal physiology. Future benefits of these studies include the Promotion and Maintenance of Good Health achieved by providing: (1) a better understanding of brain and balance disorders; (2) insights into the damaging effects of the sun and; (3) existing neonatal screening programmes for Hartnup disorder with greater scientific foundation regarding the implications of inheriting this condition, including dietary advce. We will be able to provide Australians who inherit Hartnup disorder with a better understanding of this disease by enabling individuals and families to make choices that lead to healthy, productive and fulfilling lives.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
A genetic analysis of the role of an atypical hexokinase in gene regulation. This project addresses a question which is relevant to all living things-how do changes in the environment of a cell bring about a change in gene expression? The aim of this project is to investigate the role of hexokinases in gene regulation by studying the Aspergillus nidulans xprF gene, which encodes an an unusual hexokinase. Hexokinases are thought to be the glucose sensors in plants, animals and fungi, and play a ....A genetic analysis of the role of an atypical hexokinase in gene regulation. This project addresses a question which is relevant to all living things-how do changes in the environment of a cell bring about a change in gene expression? The aim of this project is to investigate the role of hexokinases in gene regulation by studying the Aspergillus nidulans xprF gene, which encodes an an unusual hexokinase. Hexokinases are thought to be the glucose sensors in plants, animals and fungi, and play a role in the development of diabetes in humans. In plants, sugars affect many processes including growth, flowering, photosynthesis, nitrogen metabolism, starch synthesis, pigmentation and response to pathogens.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
Regulation of mammalian heart development by transcription factors FHL2, GATA-4 & FOG-2. FHL2 is involved in many biological processes including intracellular signaling and gene transcription. GATA and FOG proteins are critical for the development of diverse tissues, including the heart. Knowledge gained in this project will advance our understanding of many cellular processes, including heart development, and will contribute to our knowledge in Biology, Zoology and Veterinary Science. More spe ....Regulation of mammalian heart development by transcription factors FHL2, GATA-4 & FOG-2. FHL2 is involved in many biological processes including intracellular signaling and gene transcription. GATA and FOG proteins are critical for the development of diverse tissues, including the heart. Knowledge gained in this project will advance our understanding of many cellular processes, including heart development, and will contribute to our knowledge in Biology, Zoology and Veterinary Science. More specifically, it will contribute to Stem Cell research, a 'hot' area in the biotechnology industry, particularly towards building a strong base of expertise, skills and technological capability in this new field, and may even lead to the development of a commercial product e.g. a heart muscle cell-coated biomaterial to aid failing heart.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
Linking mutant zebrafish phenotypes with their underlying genetic lesions. Zebrafish mutants have been generated with many interesting abnormalities, but to understand these abnormalities, the defective genes must be identified by positional cloning. We seek to identify the defective genes underpinning four mutants. Mutant #562 develops a normal nervous system which then undergoes rapid degeneration. The mutant flotte lotte has abnormal gut development. Two mutants with defective early blood for ....Linking mutant zebrafish phenotypes with their underlying genetic lesions. Zebrafish mutants have been generated with many interesting abnormalities, but to understand these abnormalities, the defective genes must be identified by positional cloning. We seek to identify the defective genes underpinning four mutants. Mutant #562 develops a normal nervous system which then undergoes rapid degeneration. The mutant flotte lotte has abnormal gut development. Two mutants with defective early blood formation will be studied. We will establish techniques for several steps that will be useful for all zebrafish mapping projects. We expect the genetic characterization of these mutants to provide new insights into nerve cell survival, gut development, and blood formation.Read moreRead less
Molecular control of embryonic patterning: The function of Rhou gene in mediating response to WNT signalling. The scientific knowledge gained from this investigation of the early development of embryos will inform us of how the essential building blocks of the body are assembled, and provide insights into the genetic and developmental causes of birth defects. This will benefit the health professionals, the research community, the education sector and the general public, by underpinning the form ....Molecular control of embryonic patterning: The function of Rhou gene in mediating response to WNT signalling. The scientific knowledge gained from this investigation of the early development of embryos will inform us of how the essential building blocks of the body are assembled, and provide insights into the genetic and developmental causes of birth defects. This will benefit the health professionals, the research community, the education sector and the general public, by underpinning the formulation of new research hypotheses, enriching the curriculum and the provision of informed counselling. The embryological expertise developed for this project will enhance the nation's research capability through the sharing of skills and knowledge with a national network of academic and industrial research teams. Read moreRead less