Structural And Functional Analysis Of A Cancer-linked Co-regulator Complex
Funder
National Health and Medical Research Council
Funding Amount
$729,571.00
Summary
We seek to understand the mechanisms by which genes are switched on and off throughout our lifetime. A number of multi-component protein machines are involved in this process but their make-up and mechanism of action is not understood. We will investigate the structure and function of one of these machines that has been strongly linked to cancer.
Epigenetic Regulation By PKC-theta In Human Breast Cancer Stem Cells.
Funder
National Health and Medical Research Council
Funding Amount
$818,132.00
Summary
Treating women with advanced breast cancer is difficult, and new drugs are needed to kill the cancer stem cells that cause recurrence. We think that a newly discovered protein, PKC-?, plays an important role in recurring breast cancer and can be targeted using novel ‘epigenetic’ drugs. Here, we will use cutting-edge DNA techniques to learn how this protein controls how cancer cells grow and produce the necessary data to show that targeting this protein is likely to be effective in real patients.
The Role Of Capsid Protein Nucleolar Localisation In Chikungunya Virus: Implications For Vaccine Development
Funder
National Health and Medical Research Council
Funding Amount
$520,520.00
Summary
Chikungunya virus (CHIKV) is a globally widespread mosquito-borne alphavirus capable of causing considerable human morbidity and mortality. With no CHIKV vaccine or antiviral available this proposal aims to develop a live attenuated CHIKV vaccine, rationally designed by investigating the host cell nucleolar trafficking of CHIKV capsid protein. This vaccine has the potential to provide cross-protection against additional arthritogenic alphaviruses endemic to Australia such as Ross River virus.
Genomic Analysis Of DNA Binding And Gene Regulation By The Chromatin Remodelling Factor UBF
Funder
National Health and Medical Research Council
Funding Amount
$624,254.00
Summary
Synthesis of ribosomes, the cellular protein synthetic machinery, is the major anabolic event of a growing cell and is frequently dysregulated during disease such as cancer. This grant will examine a protein termed UBF that we think plays an important role in orchestrating the cellular response to dysregulated ribosome biogenesis. By understanding how UBF functions we hope to uncover novel therapeutic approaches to treat diseases associated with ribosome stress .
Regulation Of Ribosomal RNA Gene Chromatin During Malignant Transformation.
Funder
National Health and Medical Research Council
Funding Amount
$882,486.00
Summary
The overarching goal of this proposal is to determine the molecular basis for tumour cell dependence on activated ribosomal RNA gene repeats (rDNA). Our working model posits that rDNA repeats become activated through changes in rDNA chromatin structure that include increased binding of the RNA Polymerase I transcription factor UBF.
Regulation Of Receptors That Control Platelet Function Under Shear Stress
Funder
National Health and Medical Research Council
Funding Amount
$507,273.00
Summary
Specialized human blood cells that control blood loss and clotting (platelets) are currently difficult to test in the clinical laboratory, meaning patients are at risk of excessive bleeding or serious clot formation during disease or treatment. The aim of this proposal is to use our new reagents and assays to develop more reliable methods for evaluating relative bleeding or clotting risk in individuals.
Autoimmune-based thrombocytopenia can be a life-threatening adverse event associated with viral load, surgery, drug therapies or the use of the anticoagulant, heparin. This grant will define mechanisms of anti-platelet antibody-dependent platelet activation and assess shedding of platelet-specific glycoprotein (GP)VI as an immediate consequence of this activation, provide a new strategy for evaluating risk of thrombosis in HIT.
The Role Of Duffy And PF4 In The Platelet Killing Of Malaria Parasites.
Funder
National Health and Medical Research Council
Funding Amount
$350,045.00
Summary
Platelets in the blood can kill the Plasmodium parasite, which lives inside red blood cells and causes malaria. Platelets bind parasite-infected red cells and release a molecule that is toxic to the parasite. This project will study why a red cell molecule called Duffy is also needed for this function of platelets. Most Africans carry a gene for Duffy that stops its expression in red cells, and may therefore be more susceptible to malaria because their platelets cannot kill the malaria parasite.
Role Of SPPL2A On B Cell Survival And Antibody Production In Mice And Humans
Funder
National Health and Medical Research Council
Funding Amount
$592,989.00
Summary
B lymphocytes are a specialised type of blood cells that produce antibodies in response to a pathogen or a vaccine. We have recently discovered that all mature B cells depend for their survival on a previously unknown protein called SPPL2A. This application will investigate the molecular mechanism through which SPPL2A contributes to the survival of B cells. We will also investigate if humans with currently unexplained B cell deficiency have mutations in SPPL2A.
Cholestasis And Hepatocyte Injury In Chronic Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$615,967.00
Summary
The aim of this project is to understand the consequences of long-term cholestasis or impaired bile excretion/flow on normal liver cells (hepatocytes) and to test whether specific bile acids can cause irreversible damage to hepatocytes leading to their transformation into pre-malignant cells and hepatocellular carcinoma (primary liver cancer). The results from this project will inform new strategies in screening, prevention and treatment of liver cancer in children and adults with cholestasis.