Roles Of Ndfip1 And Ndfip2 As Adaptors For The Nedd4 Family Of Ubiquitin Ligases
Funder
National Health and Medical Research Council
Funding Amount
$656,395.00
Summary
Part of this proposal is to understand how the body controls iron uptake through one of the iron transporters (DMT1). We will also study how proteins called Ndfip1 and Ndfip2 that regulate DMT1, also control other cellular processes, such as protection against brain damage following trauma. The results from this study should ultimately contribute to the development of therapies for certain human pathologies.
Identification of Proteins that Regulate Apoptosis Through Interaction With IAPS. Apoptosis is the process by which multicellular organisms eliminate unwanted cells. Identifying proteins involved in cell death regulation is central to our understanding of disease states arising from aberrations in this process. The mammalian protein DIABLO, promotes cell death by interacting with and antagonising inhibitor of apoptosis proteins (IAPS). Given the existence of several IAP regulatory proteins (IRPs ....Identification of Proteins that Regulate Apoptosis Through Interaction With IAPS. Apoptosis is the process by which multicellular organisms eliminate unwanted cells. Identifying proteins involved in cell death regulation is central to our understanding of disease states arising from aberrations in this process. The mammalian protein DIABLO, promotes cell death by interacting with and antagonising inhibitor of apoptosis proteins (IAPS). Given the existence of several IAP regulatory proteins (IRPs) in insects, other mammalian IRPs probably also exist. These may be of equal importance in regulating apoptosis, especially in tissues where DIABLO is not expressed. The main aim of the proposed study is to idenitify and characterise other IRPs in mammalian cells.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0226463
Funder
Australian Research Council
Funding Amount
$160,000.00
Summary
Fluorescence Lifetime Imaging Facility. The aim of this proposal is to establish the first fluorescence lifetime imaging facility (FLIM) in Australia. The imaging technique provided by the new facility when combined with the use of novel fluorescent protein technology will enable many different events, represented by protein-protein interactions, to be non-invasively, visualised spatially and temporally inside the living cell. The new facility will provide timely state-of -the-art infrastructu ....Fluorescence Lifetime Imaging Facility. The aim of this proposal is to establish the first fluorescence lifetime imaging facility (FLIM) in Australia. The imaging technique provided by the new facility when combined with the use of novel fluorescent protein technology will enable many different events, represented by protein-protein interactions, to be non-invasively, visualised spatially and temporally inside the living cell. The new facility will provide timely state-of -the-art infrastructure necessary for research groups to further develop and maintain their international reputations, will build stronger research collaborations between partner institutions and will attract researchers from overseas.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
Regulation Of BRCA1 And APC Tumour Suppressor Functions By Nuclear Export
Funder
National Health and Medical Research Council
Funding Amount
$433,500.00
Summary
Cancer cells are unique, in that their ability to divide and grow is no longer controlled. Moreover, the DNA of cancer cells is less stable, and vital control genes often gain small mutations which culminate in a more aggressive or malignant cancer cell. Cancers from different tissues progress and respond in different ways to treatment, and the eventual development of tailored treatments or therapies will require a detailed understanding of how cancers from different tissues arise. Our laborator ....Cancer cells are unique, in that their ability to divide and grow is no longer controlled. Moreover, the DNA of cancer cells is less stable, and vital control genes often gain small mutations which culminate in a more aggressive or malignant cancer cell. Cancers from different tissues progress and respond in different ways to treatment, and the eventual development of tailored treatments or therapies will require a detailed understanding of how cancers from different tissues arise. Our laboratory studies two proteins, BRCA1 and APC, which are encoded by the genes most often associated with breast and colon cancer, respectively. We have made important discoveries linking the movement and location of these proteins inside the cell with their cancer-causing activity. In this project, we will continue to study how and why APC and BRCA1 move between different compartments inside cancer cells, and how this movement can sometimes signal cancer cells to die. Detailed understanding of these processes is essential for the eventual design of drug, peptide or gene therapies aimed at correcting defects in the expression or localisation of APC or BRCA1 in breast or colon cancer cells, and hopefully provide clues for that magic bullet that specifically targets and kills cancer cells.Read moreRead less
The function of truncated MEK1 protein in a G2 phase cell cycle delay and in mitosis. Understanding cell proliferation. Intracellular signaling pathways controlling cell growth are often mutated in cancers and other hyperproliferative diseases. Understanding precisely how these pathways operate and how mutations of these pathways can contribute to uncontrolled growth can readily provide new targets for preventative therapies or cures. We have identified a novel mechanism regulating one compone ....The function of truncated MEK1 protein in a G2 phase cell cycle delay and in mitosis. Understanding cell proliferation. Intracellular signaling pathways controlling cell growth are often mutated in cancers and other hyperproliferative diseases. Understanding precisely how these pathways operate and how mutations of these pathways can contribute to uncontrolled growth can readily provide new targets for preventative therapies or cures. We have identified a novel mechanism regulating one component of a well studied pathway, the MAPK pathway, and new functions for this component. The contribution of this novel component to mechanisms involved in regulating cell growth previously through to be controlled by the canonical MAPK pathway could change our understanding of the fundamental mechanisms controlling cell growth. Read moreRead less
Function of the unique mitotic form of MEK. Many of the mechanisms controlling normal cell growth and division are known, although there are an increasing number of examples of mechanism having more thn the originally defined functions. We have found that one well studied mechanism, the Ras-Raf-MEK-ERK pathway operates in a unique manner during the phase when cell division occurs, known as mitosis. Understanding this novel mechanism and identifying its function at this critical stage of cell d ....Function of the unique mitotic form of MEK. Many of the mechanisms controlling normal cell growth and division are known, although there are an increasing number of examples of mechanism having more thn the originally defined functions. We have found that one well studied mechanism, the Ras-Raf-MEK-ERK pathway operates in a unique manner during the phase when cell division occurs, known as mitosis. Understanding this novel mechanism and identifying its function at this critical stage of cell division will provide insights into how cell control the partitioning of replicated genome and produce two identical daugther cells.Read moreRead less
The role of heparan sulfate proteoglycans in the control of osteoblast phenotype. Very little is known about how bone cells progress from a naive precursor state, through differentiation and then maturation into adult cells. We wish to purify sugars from the bone cell membrane, extracellular matrix and culture medium, and examine the cellular response following the addition of these various sugar fractions to osteoblast cell cultures in combination with known growth factors. If we can control ....The role of heparan sulfate proteoglycans in the control of osteoblast phenotype. Very little is known about how bone cells progress from a naive precursor state, through differentiation and then maturation into adult cells. We wish to purify sugars from the bone cell membrane, extracellular matrix and culture medium, and examine the cellular response following the addition of these various sugar fractions to osteoblast cell cultures in combination with known growth factors. If we can control the progression of osteoblastic cells through the phases of recruitment, proliferation, differentiation and maturation by the addition of specific sugar fractions then we can potentially control bone formation.Read moreRead less
Myofibroblast differentiation: from haemopoietic cells to smooth muscle. Until very recently the ability of adult cells with specific differentiated functions to re-differentiate for another function was thought to be extremely limited. However we have shown that cells ultimately derived from the bone marrow can differentiate into fibroblasts, then into myofibroblasts and then into smooth muscle cells. This project will build on these unique findings and determine the molecular mechanisms cont ....Myofibroblast differentiation: from haemopoietic cells to smooth muscle. Until very recently the ability of adult cells with specific differentiated functions to re-differentiate for another function was thought to be extremely limited. However we have shown that cells ultimately derived from the bone marrow can differentiate into fibroblasts, then into myofibroblasts and then into smooth muscle cells. This project will build on these unique findings and determine the molecular mechanisms controlling this process. We hypothesise that the local environment of a cell is critical and will involve a combination of particular extracellular matrix and growth factors as well as mechanical tension and the presence of other cell types.Read moreRead less
Factors involved in release of cytochrome c from mitochondria during apoptosis. Mitochondria are energy-producing organelles that activate cell death by selective release of constituents, notably cytochrome c, which participate in death-signalling cascades. I aim to probe such mitochondrial release mechanisms in intact cells, by focussing on features of translocated proteins relevant to release. Cultured mouse cells lacking cytochrome c are uniquely suited to these studies. A series of cytochrom ....Factors involved in release of cytochrome c from mitochondria during apoptosis. Mitochondria are energy-producing organelles that activate cell death by selective release of constituents, notably cytochrome c, which participate in death-signalling cascades. I aim to probe such mitochondrial release mechanisms in intact cells, by focussing on features of translocated proteins relevant to release. Cultured mouse cells lacking cytochrome c are uniquely suited to these studies. A series of cytochrome c derivatives will be engineered in elongated or aggregated forms and their release studied (including interactions with putative release machinery components) following death-signal activation. The project will elucidate a central mechanism in the cell death process, highly significant in many biological contexts.Read moreRead less