Co-ordinated Action of ATM and DNA-PK in DNA damage recognition. The aim of this project is to investigate the mechanism of repair of double straind breaks in DNA sustained after radiation damage. Specifically we will focus on two proteins ATM (mutated in the genetic disorder ataxia-telangiectasia) and DNA-PK mutated in scid mice. There two proteins recognize double straind breaks in DNA and signal this damage to the DNA repair machinery of the cell and to cell cycle checkpoints. The emphasis ....Co-ordinated Action of ATM and DNA-PK in DNA damage recognition. The aim of this project is to investigate the mechanism of repair of double straind breaks in DNA sustained after radiation damage. Specifically we will focus on two proteins ATM (mutated in the genetic disorder ataxia-telangiectasia) and DNA-PK mutated in scid mice. There two proteins recognize double straind breaks in DNA and signal this damage to the DNA repair machinery of the cell and to cell cycle checkpoints. The emphasis here will be in the relationship between the two proteins in co-ordinating the repair of breaks in DNA. This information will be important in understanding mechanisms for maintaining the integrity of the genome.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
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
Transcriptional and epigenetic regulation of terminal lymphocyte differentiation and alterations of the same that lead to leukemia. In the developed world infection diseases are the number three killer behind heart disease and cancer, and huge financial effort is put into treatment and prevention. Despite this, results have often been disappointing. One cause of these poor outcomes is the lack of knowledge of how effective immune responses are generated. This project aims to better understand th ....Transcriptional and epigenetic regulation of terminal lymphocyte differentiation and alterations of the same that lead to leukemia. In the developed world infection diseases are the number three killer behind heart disease and cancer, and huge financial effort is put into treatment and prevention. Despite this, results have often been disappointing. One cause of these poor outcomes is the lack of knowledge of how effective immune responses are generated. This project aims to better understand the processes that control the generation of protective lymphocytes. It will deliver information that may enable a more targeted approach to vaccine-development and treatments of infections. As defective differentiation can also be a cause of leukemia it may also lead to targets of cancer treatment.Read moreRead less
Identification of genes regulating breast cancer progression and metastasis. Breast cancer is the most common cause of cancer-related death in women in Australia. Although the treatments have improved over the last thirty years, many women still die from relapse of the disease. Our goal is to identify genes involved in the regulation of breast cancer progression and metastasis. This may lead to the discovery of druggable molecules for better targeted therapies for patients.
New functions for bioactive flavonoids in plants and mammals. We have discovered natural products with biological activity in plants and mammals. These molecules affect plant shape and development and the process of mammalian blood vessel formation. We seek to understand how these molecules work. More understanding is required before one can begin to utilise these molecules for possible beneficial agriculture or human health outcomes. Plant shape influences such things as yield or more drought-r ....New functions for bioactive flavonoids in plants and mammals. We have discovered natural products with biological activity in plants and mammals. These molecules affect plant shape and development and the process of mammalian blood vessel formation. We seek to understand how these molecules work. More understanding is required before one can begin to utilise these molecules for possible beneficial agriculture or human health outcomes. Plant shape influences such things as yield or more drought-resilient root systems. Importantly, we have discovered specific molecules that either promote or inhibit blood vessel formation. A better understanding of how these molecules work could lead to novel treatments for cancer or cardiovascular disease.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
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
The role of human single-stranded binding protein (hSSB1) in DNA damage repair and tumorogenesis. Cancer is a leading cause of disease related death world wide, accounting for over 13% of all deaths in 2007. Approximately 38,000 people died in Australia from cancer in 2005. Cancer results from a single cell losing a vital part of its genetic information, this results in the cell losing its normal programming and initiates a process of rapid growth and multiplication. This research project aims t ....The role of human single-stranded binding protein (hSSB1) in DNA damage repair and tumorogenesis. Cancer is a leading cause of disease related death world wide, accounting for over 13% of all deaths in 2007. Approximately 38,000 people died in Australia from cancer in 2005. Cancer results from a single cell losing a vital part of its genetic information, this results in the cell losing its normal programming and initiates a process of rapid growth and multiplication. This research project aims to look at the mechanisms that exist to prevent this initial loss of genetic material within an individual cell. It further aims to translate theses discoveries into the clinic, providing new tools for diagnosis and prognosis of specific cancers and to establish links with major pharmaceutical companies to develop novel anticancer therapies.Read moreRead less