The Role Of Ikaros In Establishing Regulatory Networks For Lymphocyte Development
Funder
National Health and Medical Research Council
Funding Amount
$345,809.00
Summary
Ikaros is a protein that regulates gene expression during development of lymphocytes from blood stem cells. Ikaros has a profound importance in normal and malignant lymphocyte development, but we still do not know how it controls these processes. The aim of my study is to identify genes regulated by Ikaros and the molecular mechanisms of their regulation. This study will contribute to understanding of the regulatory network controlling the development and function of lymphocytes.
Molecular analysis of photosynthetically-linked, active CO2 uptake and CO2 signal transduction by cyanobacteria (blue-green algae). Cyanobacteria (blue-green algae) have evolved a very efficient means of capturing and concentrating CO2 for photosynthetic fixation into sugars, the basic building blocks for cell growth. This process is dependent on the operation of several unique, active uptake systems for CO2 and HCO3-, with their genetic expression regulated by CO2 supply. This proposal will cap ....Molecular analysis of photosynthetically-linked, active CO2 uptake and CO2 signal transduction by cyanobacteria (blue-green algae). Cyanobacteria (blue-green algae) have evolved a very efficient means of capturing and concentrating CO2 for photosynthetic fixation into sugars, the basic building blocks for cell growth. This process is dependent on the operation of several unique, active uptake systems for CO2 and HCO3-, with their genetic expression regulated by CO2 supply. This proposal will capitalize on our progress in describing the functional genetics of this process and aims to elucidate the mechanism of active CO2 uptake and the way that cells sense the ambient CO2 concentration. The information gained is likely to be useful for designing improved crops.Read moreRead less
Combinatorial controlled gene expression delivering crops resistant to nematodes. Root-knot nematodes cause US$130 billion crop losses worldwide pa, and at least AUS$ 450 pa in Australia. Current control methods involve fumigation, chemicals (mainly carbamates and organophosphates), natural plant resistance and biological control. The fumigants (eg methyl bromide) are being phased out because they damage the ozone layer, most of the non-fumigants are being banned because of environmental damag ....Combinatorial controlled gene expression delivering crops resistant to nematodes. Root-knot nematodes cause US$130 billion crop losses worldwide pa, and at least AUS$ 450 pa in Australia. Current control methods involve fumigation, chemicals (mainly carbamates and organophosphates), natural plant resistance and biological control. The fumigants (eg methyl bromide) are being phased out because they damage the ozone layer, most of the non-fumigants are being banned because of environmental damage and persistence in groundwater, and biological control has had limited success. These problems are addressed in this project with development of synthetic plant resistance to nematodes, which will benefit horticultural and broadacre farming by reducing pathogen losses and improving quality.Read moreRead less
All cells in the blood are the descendants of a single cell type, the stem cell. Stem cells are found in the bone marrow and throughout life have the unique ability to generate more of themselves (termed self-renewal) as well as to produce the functional cell types of the blood, ie. red and white blood cells. This project concentrates on the processes by which these stem cells can achieve these two functions. What are the genes that enable a stem cell to have this self-renewal characteristic and ....All cells in the blood are the descendants of a single cell type, the stem cell. Stem cells are found in the bone marrow and throughout life have the unique ability to generate more of themselves (termed self-renewal) as well as to produce the functional cell types of the blood, ie. red and white blood cells. This project concentrates on the processes by which these stem cells can achieve these two functions. What are the genes that enable a stem cell to have this self-renewal characteristic and conversely what are the genes that are activated when a cell becomes committed to become, for example, a white blood cell ? We have identified a gene, Pax5, which is essential in the process whereby a stem cell commits to become a lymphocyte . Our aim is to understand the function of Pax5 as a model for understanding how the commitment process as a whole works in the blood. These studies, as well as having an underlying fundamental scientific importance, are relevant to the clinical development of a number of stem cell therapies which rely on boosting stem cell production in procedures such as bone marrow transplantation for leukaemia and immune deficiency. In addition a number of characterised human blood malignancies indicate that inappropriate lineage commitment may be a factor in cancer.Read moreRead less
Osteoporosis is a pathological loss of bone that affects many Australians. It occurs because of an excessive release of calcium from bone that is caused by the overactivity of the cells that break down bone, osteoclasts. We have studied two genes that are involved in the way these cells work and by a close examination of the the way they are regulated we hope to understand how osteoclasts are derived and how their activity is controlled. In particular we will look at two newly dicovered osteocla ....Osteoporosis is a pathological loss of bone that affects many Australians. It occurs because of an excessive release of calcium from bone that is caused by the overactivity of the cells that break down bone, osteoclasts. We have studied two genes that are involved in the way these cells work and by a close examination of the the way they are regulated we hope to understand how osteoclasts are derived and how their activity is controlled. In particular we will look at two newly dicovered osteoclast regulators called PPAR-gamma and PPAR-delta. These offer the opportunity for the development in the future of new, alternative drugs for the treatment of osteoporosis.Read moreRead less
In this grant we aim to study the moecular basis of cancer. The promoter regions of tumour suppressor genes are often modified in cancer by a chemical process called methylation. Methylation of DNA is associated with gene silencing. Therefore DNA methylation is commonly regarded as causing the silencing of genes in cancer. In this grant, we aim to determine if methylation is causal in triggering gene silencing in cancer, or if methylation is a consequence of gene silencing. This is a critical di ....In this grant we aim to study the moecular basis of cancer. The promoter regions of tumour suppressor genes are often modified in cancer by a chemical process called methylation. Methylation of DNA is associated with gene silencing. Therefore DNA methylation is commonly regarded as causing the silencing of genes in cancer. In this grant, we aim to determine if methylation is causal in triggering gene silencing in cancer, or if methylation is a consequence of gene silencing. This is a critical distinction in understanding the role of methylation in cancer development.Read moreRead less
The link between environmental stress and disease onset in prawn aquaculture. The federal government has set a target for prawn aquaculture production to increase fourfold by 2010. A major barrier is disease: losses of 20% of production to viral diseases are not uncommon. To be internationally competitive, Australia needs to develop high health production systems. Most prawn stock carry chronic viral infections, but only exhibit disease symptoms following environmental stress. This project will ....The link between environmental stress and disease onset in prawn aquaculture. The federal government has set a target for prawn aquaculture production to increase fourfold by 2010. A major barrier is disease: losses of 20% of production to viral diseases are not uncommon. To be internationally competitive, Australia needs to develop high health production systems. Most prawn stock carry chronic viral infections, but only exhibit disease symptoms following environmental stress. This project will identify environmental stressors that activate viral disease in Penaeus monodon. Outcomes will be incorporated into on-farm managerial regimes to minimize risk of crop loss to disease. Development of biomarkers as indicators of stress related risks may be commercialized.Read moreRead less
Inferring Global Regulatory Architecture Of Human Gene Expression In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$47,427.00
Summary
Our genome encodes ~25,000 genes that shape out an individual from head to toe. Malfunction of a particular gene could cause fatal health problem or disease. Nonetheless, the mis-regulation of functioning genes can also result in serious diseases. In this study, we are going to use large-scale gene regulation information and advanced computing techniques to clarify the regulation network of human genome on a global level. Hence, helping us to understand more about diseases of gene transcription.
PKC-zeta-dependent Sp1 Phosphorylation: Regulatory Insights using Novel Phospho-Specific Sp1 Antibodies and Peptide Decoys. This project will demonstrate the value of novel phospho-specific Sp1 antibodies and phospho-Sp1 peptide decoys as new molecular tools to provide invaluable insights into the regulatory roles of phosphorylated Sp1 in the control of gene expression, an area poorly defined at the present time. These agents will be used to increase our fundamental understanding of Sp1 activity ....PKC-zeta-dependent Sp1 Phosphorylation: Regulatory Insights using Novel Phospho-Specific Sp1 Antibodies and Peptide Decoys. This project will demonstrate the value of novel phospho-specific Sp1 antibodies and phospho-Sp1 peptide decoys as new molecular tools to provide invaluable insights into the regulatory roles of phosphorylated Sp1 in the control of gene expression, an area poorly defined at the present time. These agents will be used to increase our fundamental understanding of Sp1 activity by identifying physiologic agonists of the PKC-zeta-phospho-Sp1 axis and FasL-dependent apoptosis, interactions of phospho-Sp1 with the authentic FasL promoter and its recruitment of collaborative factors. The commercial exploitation of phospho-specific Sp1 antibodies and phospho-Sp1 peptide decoys will generate economic returns to Australia.Read moreRead less