A New Model for 3D Migration Involving Claw Structures and Metalloproteinases. This proposal will revolutionize ideas related to cell movement through three-dimensional (3D) matrix. Our method in mimicking the body's dense 3D matrix environment have led to the discovery of a new cell structure called Claws, and the formulation of a new model for 3D invasion in high density matrix. We will study the genes that control this type of migration including those involved in the formation of the cell fr ....A New Model for 3D Migration Involving Claw Structures and Metalloproteinases. This proposal will revolutionize ideas related to cell movement through three-dimensional (3D) matrix. Our method in mimicking the body's dense 3D matrix environment have led to the discovery of a new cell structure called Claws, and the formulation of a new model for 3D invasion in high density matrix. We will study the genes that control this type of migration including those involved in the formation of the cell front (Claw region), the back of the cells and matrix digestion. This work will have significant impact on normal and pathological human conditions from immune responses to tissue regeneration and cancer.Read moreRead less
Function of a new splicing factor, RBM4. New genomic knowledge is revolutionizing our world. However our understanding of the basic mechanisms of RNA maturation, especially regulation of splicing lags significantly behind our understanding of related genomic processes. This project is a genetic approach to help elucidate the function of new splicing factors and characterize the way in which specific RNA sequences are recognized. It should promote the better understanding of regulatory events inv ....Function of a new splicing factor, RBM4. New genomic knowledge is revolutionizing our world. However our understanding of the basic mechanisms of RNA maturation, especially regulation of splicing lags significantly behind our understanding of related genomic processes. This project is a genetic approach to help elucidate the function of new splicing factors and characterize the way in which specific RNA sequences are recognized. It should promote the better understanding of regulatory events involved in controlling gene expression during development and differentiation. Results from this project will also provide new insights into the 'multifunctionality' of cellular proteins and will illustrate the importance of RNA studies in molecular medicine.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
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
Tissue specific regulation of gene expression. Despite the polarized public debate concerning the use of stem cells for tissue regeneration, fundamental questions relating to the identity and hierarchy of these cells remain unanswered. The benefit to Australia will be scientific in terms of providing an understanding of how stem and progenitor cells integrate transcriptional control systems during differentiation and the networks that are involved. This is fundamental to the future isolation a ....Tissue specific regulation of gene expression. Despite the polarized public debate concerning the use of stem cells for tissue regeneration, fundamental questions relating to the identity and hierarchy of these cells remain unanswered. The benefit to Australia will be scientific in terms of providing an understanding of how stem and progenitor cells integrate transcriptional control systems during differentiation and the networks that are involved. This is fundamental to the future isolation and manipulation of these stem cell types to benefit the community. The work will also provide postgraduate students with training in state of the art genomic techniques and in the interface between bioinformatics and experimental science. Read moreRead less
Proteomic analysis of subcellular changes during apoptosis. This project aims to use a novel proteomic approach to examine mechanisms of apoptosis at the level of the plasma membrane, mitochondrion, nucleus and cytosol, screening protein extracts of cell organelles by the new technique of SELDI-TOF mass spectrometry in which proteins are adsorbed onto activated chips. This will provide protein mass profiles characteristic of various stages of apoptosis, and will allow identification of proteins ....Proteomic analysis of subcellular changes during apoptosis. This project aims to use a novel proteomic approach to examine mechanisms of apoptosis at the level of the plasma membrane, mitochondrion, nucleus and cytosol, screening protein extracts of cell organelles by the new technique of SELDI-TOF mass spectrometry in which proteins are adsorbed onto activated chips. This will provide protein mass profiles characteristic of various stages of apoptosis, and will allow identification of proteins of interest by conventional proteomic methods. The establishment of SELDI-MS as a viable tool for cell proteomics would open new opportunities to understand a broad range of cellular functions at the level of protein expression.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0668241
Funder
Australian Research Council
Funding Amount
$824,610.00
Summary
A Facility for High-Throughput, Functional Gene Discovery Using Arrayed Retroviral Expression Cloning. The proposed facility will represent world-leading technology in functional genomics and provide Australian scientists with unique opportunities to identify genes involved in a broad range of biological processes. This will contribute to fundamental knowledge in mammalian biology, and equally importantly, is likely to identify genes involved in important health problems such as cancer, inflamma ....A Facility for High-Throughput, Functional Gene Discovery Using Arrayed Retroviral Expression Cloning. The proposed facility will represent world-leading technology in functional genomics and provide Australian scientists with unique opportunities to identify genes involved in a broad range of biological processes. This will contribute to fundamental knowledge in mammalian biology, and equally importantly, is likely to identify genes involved in important health problems such as cancer, inflammatory disease, brain damage and diabetes. Such genes may in turn constitute targets against which new therapies may be developed. This endeavour will contribute to national research priorities in both the health and scientific/technological development arenas.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