Melanotransferrin: A “Missing Link” And A Novel Pharmacological Target For Treatment
Funder
National Health and Medical Research Council
Funding Amount
$613,848.00
Summary
Despite >30 years of research, the precise function of the protein, melanotransferrin (MTf), is unknown. However, we have breakthrough evidence that MTf stimulates WNT signalling as a major driver in cancer progression. We will investigate this hypothesis, which will underpin new cancer therapies. Indeed, we designed a new class of drugs that target the WNT pathway via up-regulating the WNT inhibitor, NDRG1. This drug (DpC) inhibits MTf expression to block tumour cell growth and metastasis.
Heparin-induced Thrombocytopenia And Thrombosis: Better Understanding Of Pathogenesis And Improving Diagnosis And Treatment
Funder
National Health and Medical Research Council
Funding Amount
$653,137.00
Summary
Heparin, a widely used drug, can cause an adverse effect which results in a fall of the platelet count and the development of serious thrombosis. This drug complication is mediated by an immune mechanism. This proposal aims to provide a better understanding of the disease mechanism. It also aims to develop a new test that will improve the diagnosis, and to produce a novel drug that will effectively suppress the immune reaction and improve the treatment.
Discovery of new genes for plant cellulose biosynthesis and improved fibre production. Cellulose, the world's most abundant biopolymer, is important to the cotton and forest industries and for human and animal nutrition. Before biotechnology can manipulate cellulose, we must identify the enzymes of the synthesis pathway and understand how their properties determine the properties of the cellulose they produce. Not all enzymes are known and any relationships to cellulose properties remain unexplo ....Discovery of new genes for plant cellulose biosynthesis and improved fibre production. Cellulose, the world's most abundant biopolymer, is important to the cotton and forest industries and for human and animal nutrition. Before biotechnology can manipulate cellulose, we must identify the enzymes of the synthesis pathway and understand how their properties determine the properties of the cellulose they produce. Not all enzymes are known and any relationships to cellulose properties remain unexplored. This study extends our successful mutational analysis of cellulose synthesis in Arabidopsis and initiates the molecular analysis of organisms making cellulose with distinctive properties. It will significantly advance knowledge of cellulose biosynthesis and identify novel genes for fibre improvement.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0453295
Funder
Australian Research Council
Funding Amount
$369,697.00
Summary
NMR cryosystem for structural and functional biology. State-of-the-art hardware is requested for the 600-MHz NMR spectrometers situated at University of Sydney and UNSW. A cryosystem installed at USyd. will provide a massive boost in productivity and will allow projects previously inaccessible due to excessive turn-around times, or sensitivity or solubility problems to become tractable. This system will provide new opportunities to researchers from USyd., UNSW and ANU, but will restrict the ver ....NMR cryosystem for structural and functional biology. State-of-the-art hardware is requested for the 600-MHz NMR spectrometers situated at University of Sydney and UNSW. A cryosystem installed at USyd. will provide a massive boost in productivity and will allow projects previously inaccessible due to excessive turn-around times, or sensitivity or solubility problems to become tractable. This system will provide new opportunities to researchers from USyd., UNSW and ANU, but will restrict the versatility of the USyd. instrument. The installation of a TBI probe at UNSW will counter this, and provide a REAL network of NMR instruments across NSW and the ACT.Read moreRead less
Pharmacology Of Potential Anti-Tumour Agents: Iron Chelators Of The BpT Class
Funder
National Health and Medical Research Council
Funding Amount
$585,455.00
Summary
Pharmacology of Potential Anti-Tumour Agents: Iron Chelators of the BpT Class Cancer cells have a high iron requirement for DNA synthesis and many clinical trials showed Fe chelators are effective anti-cancer drugs. Their potential to act as anti-tumour agents has been confirmed by the entrance of Triapine into widespread NCI clinical trials. In this NHMRC Renewal, we will perform pharmacological and preclinical studies to promote the development of BpT chelators as novel anti-tumour agents.
ADAM Metalloprotease Inhibition For Treatment Of Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$770,925.00
Summary
Colorectal cancer (CRC) causes over 4000 deaths/year, typically from developing drug resistance and spreading to other organs (metastasis). These processes involve tumour cells called cancer stem cells (CSCs), which rely on specific cell surface proteins for survival and function. We are developing antibodies against one of these type of proteins, to test in mouse models of CRC. These already show promise in targeting CSCs and inhibiting drug-resistance and metastasis in mice.
Mechanisms Of Glucocorticoid Resistance In Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$547,970.00
Summary
Glucocorticoids are extremely active drugs used in the treatment of childhood acute lymphoblastic leukaemia (ALL), yet a proportion of patients respond poorly to therapy and exhibit resistance at relapse. Clinically relevant mechanisms of glucocorticoid resistance are poorly understood, principally due to lack of appropriate experimental models. This project will reveal novel mechanisms of drug resistance in childhood leukaemia and lead to novel therapeutic strategies to improve outcome.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0454052
Funder
Australian Research Council
Funding Amount
$733,595.00
Summary
Tandem Matrix-Assisted Laser Desorption/Ionisation Time-Of-Flight Mass Spectrometer and Robots for High Throughput Proteomics Analysis. This proposal seeks to establish the capacity to perform high-energy tandem mass spectrometry on a high throughput basis, through purchase and coordinated operation of a Matrix-Assisted Laser Desorption/Ionisation - Time of Flight / Time of Flight - Mass Spectrometer and ancillary equipment, to enhance the proteomics expertise, infrastructure and research plans ....Tandem Matrix-Assisted Laser Desorption/Ionisation Time-Of-Flight Mass Spectrometer and Robots for High Throughput Proteomics Analysis. This proposal seeks to establish the capacity to perform high-energy tandem mass spectrometry on a high throughput basis, through purchase and coordinated operation of a Matrix-Assisted Laser Desorption/Ionisation - Time of Flight / Time of Flight - Mass Spectrometer and ancillary equipment, to enhance the proteomics expertise, infrastructure and research plans of a network of institutions from Queensland and New South Wales and their collaborators. Access to such instrumentation is critical to high level achievement in proteomics, a key platform technology for National Research Priorities relating to Frontier Technologies. No comparable instrument currently exists in Australia.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0214135
Funder
Australian Research Council
Funding Amount
$492,000.00
Summary
High performance protein crystallography. This proposal will provide state of the art high performance facilities for protein crystallography, bringing together the major structural biology groups in NSW and the ACT. A renewed focus on protein crystal structures will stimulate new interpretation and utilization of the vast amount of data that has come from genomics, especially the sequencing of the human genome. The proposed facility will generate new research collaborations between the partn ....High performance protein crystallography. This proposal will provide state of the art high performance facilities for protein crystallography, bringing together the major structural biology groups in NSW and the ACT. A renewed focus on protein crystal structures will stimulate new interpretation and utilization of the vast amount of data that has come from genomics, especially the sequencing of the human genome. The proposed facility will generate new research collaborations between the partner institutions which will result in advances in basic life sciences, biotechnology and biopharmaceuticals. The facility will complement regional initiatives in functional genomics, bioinformatics, proteomics and high-field NMR spectroscopy.Read moreRead less
The molecular basis for oocyst and cyst wall formation in apicomplexan parasites. Apicomplexan parasites such as Eimeria, Neospora, Toxoplasma and Plasmodium are single celled organisms - protozoa - that cause some of the most serious infectious diseases of livestock and humans ever known. Transmission of these parasites is dependent on their ability to encase themselves in protective structures known as oocyst or cyst walls. These walls are resistant to harsh environmental conditions, chemicals ....The molecular basis for oocyst and cyst wall formation in apicomplexan parasites. Apicomplexan parasites such as Eimeria, Neospora, Toxoplasma and Plasmodium are single celled organisms - protozoa - that cause some of the most serious infectious diseases of livestock and humans ever known. Transmission of these parasites is dependent on their ability to encase themselves in protective structures known as oocyst or cyst walls. These walls are resistant to harsh environmental conditions, chemicals and attack by the immune system. We will discover and characterise the molecular basis for cyst wall formation. This fundamental knowledge will be the building block for new, highly specific drugs and vaccines to control these extremely important pathogens.Read moreRead less