Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0883068
Funder
Australian Research Council
Funding Amount
$150,000.00
Summary
Dako ACIS III Cellular Image Acquisition and Analysis System. The scientific advances that will be possible with the acquisition of this novel, cutting-edge instrument will enhance the research outputs of all investigators using it. The ability to visualize and analyze cells and tissues from many different animal species, to elucidate both normal and abnormal functions, will be enhanced by the use of this technology. This will lead to production of quantitative statistical data that in turn will ....Dako ACIS III Cellular Image Acquisition and Analysis System. The scientific advances that will be possible with the acquisition of this novel, cutting-edge instrument will enhance the research outputs of all investigators using it. The ability to visualize and analyze cells and tissues from many different animal species, to elucidate both normal and abnormal functions, will be enhanced by the use of this technology. This will lead to production of quantitative statistical data that in turn will inform new approaches to improve and maintain the health of humans and other animals.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
SPRY Domain-containing SOCS Box (SSB) Protein Interaction With Par-4: Structure And Biochemical Implications
Funder
National Health and Medical Research Council
Funding Amount
$529,565.00
Summary
The suppressor of cytokine signalling (SOCS) proteins, are intracellular molecules that negatively regulate hormone and growth factor action, and whose functional importance has been borne out in many physiological studies. The SOCS box is a small part of the SOCS proteins that is believed to facilitate degradation of SOCS target proteins. The SPRY domain-containing SOCS box protein-2 (SSB-2) is one of four proteins within the greater SOCS family (SSB-1 to -4), which have a SOCS box and a centra ....The suppressor of cytokine signalling (SOCS) proteins, are intracellular molecules that negatively regulate hormone and growth factor action, and whose functional importance has been borne out in many physiological studies. The SOCS box is a small part of the SOCS proteins that is believed to facilitate degradation of SOCS target proteins. The SPRY domain-containing SOCS box protein-2 (SSB-2) is one of four proteins within the greater SOCS family (SSB-1 to -4), which have a SOCS box and a central SPRY domain. The SPRY domain mediates interaction with other proteins within the cell. Over 300 proteins are known to contain a SPRY domain. We recently determined the first atomic structure of a SPRY domain as part of SSB-2, using nuclear magnetic resonance (NMR) spectroscopy. We further identified Par-4 (prostate apoptosis response-4) as a novel and direct protein binding partner for SSB-1, -2 and -4, but not SSB-3. Extensive mutational analysis subsequently identified a series of SSB-2 mutants that were unable to bind Par-4 but retained structural integrity. Cancer cells develop through a series of genetic events and escape programmed cell death or apoptosis, continuing to grow inappropriately. Par-4 was originally discovered as a gene up-regulated in prostate cancer cells undergoing apoptosis and primarily appears to sensitise cancer cells to apoptotic stimuli. This proposal aims to further investigate SSB-Par-4 binding. The 3D structure of the complex will be determined and biochemical consequences of this interaction characterised. If SSB proteins regulate Par-4 levels, then chemical disruption of SSB-Par-4 binding could potentially result in an increase in Par-4 protein levels, making cancer cells more susceptible to killing by cytotoxic drugs.Read moreRead less
Characterisation Of A New Family Of Proteins Involved In Cell Signalling, RNA Metabolism And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$200,880.00
Summary
We have discovered a novel RNA-binding protein (G3BP-2) that is involved in responding to external signals, such as growth factors, at the level of gene expression. Other RNA-binding proteins belonging to the same broad group of proteins are responsible for a host of disease states in mammals including mental retardation, myotonic dystrophy, Huntington?s disease and cancers. Considering the wealth of knowledge accumulated that implicates these proteins to human dysfunction surprisingly few of th ....We have discovered a novel RNA-binding protein (G3BP-2) that is involved in responding to external signals, such as growth factors, at the level of gene expression. Other RNA-binding proteins belonging to the same broad group of proteins are responsible for a host of disease states in mammals including mental retardation, myotonic dystrophy, Huntington?s disease and cancers. Considering the wealth of knowledge accumulated that implicates these proteins to human dysfunction surprisingly few of these RNA-binding proteins have been identified. We have shown that the novel protein discovered in our laboratory is perturbed in cancer and we are interested in characterising its putative role in cancer. The results established in our laboratory so far would indicate that generally, G3BP-2 is expressed in normal tissue and it expression changes in some cancers studied so far. Considering that G3BP-2 lies in a pathway known to be involved in cancer progression it is important to understand what effects the inappropriate expression of G3BP-2 may have on cancer progression and survival. This project is designed to characterise what signals the cell uses to control these proteins and in turn which genes these may effect. In this way we may be able to determine how external signals may effect tumour progression and on what genes this influence is expressed. It would be hoped that this project would increase our understanding of cancer and potentially lead to new diagnostic reagents and therapies in the treatment of cancer.Read moreRead less
The roles of novel pathways in the activation and regulation of the adaptive immune response in health and disease. The immune system is designed to protect us against infection and vaccines exploit this with great success in preventing many infections. However, the immune system can also 'fail' and attack the body in a process called autoimmunity e.g. destroying joints in rheumatoid arthritis. This proposal will define how white blood cells work to make better vaccines against infection and ho ....The roles of novel pathways in the activation and regulation of the adaptive immune response in health and disease. The immune system is designed to protect us against infection and vaccines exploit this with great success in preventing many infections. However, the immune system can also 'fail' and attack the body in a process called autoimmunity e.g. destroying joints in rheumatoid arthritis. This proposal will define how white blood cells work to make better vaccines against infection and how these same immune cells can malfunction to create autoimmune diseases like Crohn's disease.Read moreRead less
Regulation Of The Tumour Suppressors APC And BRCA1 By Nuclear Export
Funder
National Health and Medical Research Council
Funding Amount
$530,874.00
Summary
Cancer cells lack the ability to control their own growth, and thus continously divide in their local environment, leading to tumour formation. Tumour suppressor proteins, like APC and BRCA1, normally function as regulators to help cells respond to outside signals and to stop growing when necessary. The inactivation and altered cellular localisation of tumour suppressor proteins can contribute to cancer development. We have found that the APC and BRCA1 proteins, whose inactivation leads to devel ....Cancer cells lack the ability to control their own growth, and thus continously divide in their local environment, leading to tumour formation. Tumour suppressor proteins, like APC and BRCA1, normally function as regulators to help cells respond to outside signals and to stop growing when necessary. The inactivation and altered cellular localisation of tumour suppressor proteins can contribute to cancer development. We have found that the APC and BRCA1 proteins, whose inactivation leads to development of colon cancer and breast cancer, respectively, contain signals that dictate their movement within the cell. Our novel preliminary findings reveal that APC and BRCA1 are able to move in and out of the cell nucleus. We aim to define how this occurs, and examine how the regulation of their cellular location affects the normal function of these cancer-suppressing proteins. Finally, abnormalities in the nuclear passage of APC or BRCA1 might explain their altered cellular location in cancer cells.Read moreRead less
Regulated Shuttling Of Beta-catenin And IQGAP1 Between Nucleus And Plasma Membrane In Migrating Cells
Funder
National Health and Medical Research Council
Funding Amount
$511,703.00
Summary
Inherited gene mutations that cause colon cancer kill 4,700 Australians every year. About 1 in 21 Australians develop colorectal cancer by age 75. Activation of the beta-catenin protein is a critical switch in the path to colon cancer. We discovered that beta-catenin, and another protein it interacts with called IQGAP1, move between different cellular compartments. We plan to study this process in more detail, as it relates to how beta-catenin works and to understanding its role in cancer.
Targeting Of The APC Tumour Suppressor To Mitochondria: Implications For APC Regulation And Cellular Function
Funder
National Health and Medical Research Council
Funding Amount
$390,116.00
Summary
Inherited mutations in the APC gene cause colon cancer, and kills 4,700 Australians every year. About 1 in 21 Australians develop colorectal cancer by the age of 75. APC mutations change cells in different ways, triggering the cancer process. We have discovered a new pathway, involving altered movement of APC to mitochondria in tumour cells. This study will investigate how this cancerous change may help our understanding of colon cancer progression.
The regulated movement of membrane receptors and ligands between the cell surface and intracellular compartments is vital to many cellular operations, including communication between cells and their environment. However, the molecular details of these sorting events remain poorly defined. Determination of the mechanisms that control the cellular distribution of receptors is critical for understanding normal cellular processes and in pathological processes like tumorigenesis.