Elucidating The Mechanisms Of Action Of And Resistance To Endoperoxide Antimalarials
Funder
National Health and Medical Research Council
Funding Amount
$716,755.00
Summary
Artemisinin-based antimalarials (ARTs) save hundreds of thousands of lives every year. Unfortunately resistance of P. falciparum to ART is now emerging in South East Asia and it is critical to know how and why. We will determine what is different about resistant parasites and will develop assays to monitor drug resistance in the field. We have found that the immature form of the malaria parasite is more resistant to ARTs, which helps explain resistance. We will build on this to develop new targe ....Artemisinin-based antimalarials (ARTs) save hundreds of thousands of lives every year. Unfortunately resistance of P. falciparum to ART is now emerging in South East Asia and it is critical to know how and why. We will determine what is different about resistant parasites and will develop assays to monitor drug resistance in the field. We have found that the immature form of the malaria parasite is more resistant to ARTs, which helps explain resistance. We will build on this to develop new targetted treatments.Read moreRead less
Investigation Of Lipid-protein Interactions Of Mechanosensitive Ion Channels
Funder
National Health and Medical Research Council
Funding Amount
$409,785.00
Summary
Living organisms are imminently exposed to mechanical stimuli such as gravity, touch or sound. Sensing mechanical stimuli is therefore crucial for survival. One biological tool for sensing mechanical stress are the mechanosensitive ion channels that open in response to tension in cell membranes. We will study the interactions and coupling between membrane lipids and mechanosensitive ion channels. These interactions are essential for the function of these fascinating sensory biological molecules.
The Essential Nuclear Transporter Importin 13; Key Role In Brain And Testis
Funder
National Health and Medical Research Council
Funding Amount
$613,124.00
Summary
Transport into and out of the nucleus, the control centre of cells, is critical for cell function in complex organisms such as mammals. The present proposal seeks to further understanding of a novel molecule mediating nuclear transport that has a novel inhibitory form in the testis, and important roles in the lung and nervous system. The results should help basic understanding of this molecule, and relate to disease conditions such as X-linked mental retardation and childhood asthma.
Characterising The Beta-catenin Nuclear Targeting Pathway In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$485,081.00
Summary
Bowel cancer is caused by inherited gene mutations that cause build-up of beta-catenin protein in the cell nucleus. Bowel cancer is the second largest cause of cancer deaths in Australia. We aim to study the mechanisms controlling beta-catenin accumulation in the nucleus. We will characterise new signalling pathways that control movement and activity of beta-catenin in the nucleus. This will yield insights into the role of beta-catenin in cancer and possible targets for therapy.
Mechanism And Treatment Of Sympathetically Maintained Pain
Funder
National Health and Medical Research Council
Funding Amount
$482,962.00
Summary
This project investigates a crucial but neglected element in the mechanism of chronic pain that develops after nerve and tissue injury. In particular, our aim is to establish whether expression of a chemical target of the neurotransmitter noradrenaline increases in the painful skin of affected patients, and whether medication that blocks this target alleviates inflammation and pain. If so, this may open up new avenues for treatment for previously intractable pain syndromes.
Breaking Malaria's Lethal Grip: Targeting The Assembly Of An Adhesive Complex On Infected Red Blood Cells
Funder
National Health and Medical Research Council
Funding Amount
$817,426.00
Summary
The malaria parasite, Plasmodium falciparum, infects the red blood cells of its human victims. It causes them to stick to blood vessel walls in the brain, causing severe cerebral complications and death. Adhesion is mediated by a Velcro-like protein that is presented at the red blood cell surface. This project will fully elucidate the pathway for trafficking of the adhesion protein to the red blood cell surface with a view to finding new ways of interfering with malaria disease.
Architecture Of The Hendra Virus Nucleocapsid And Implications For Replication
Funder
National Health and Medical Research Council
Funding Amount
$342,108.00
Summary
Hendra virus causes sporadic fatal outbreaks in horses, which may result in human deaths through direct contact with infected animals. The unanticipated surge of Hendra cases since mid-2011, the broad host range of the virus and the discovery of other related viruses worldwide highlight the epidemic potential of hendra-related paramyxoviruses. To improve our preparedness against paramyxoviruses, this Project aims at determining the structure of the viral replication machinery.
Antibiotic resistant bacteria cause life-threatening diseases and represent a major public health problem. Globally, drug-resistant infections currently cause over 500,000 deaths annually and this figure is projected to exceed 10 million by 2050. Venom peptides are a new avenue of antibiotic discovery. This proposal aims to define how these peptides interact with the cellular power generator, ATP synthase, to provide a basis for exploiting their potential to treat bacterial infections.
Signalling Mechanisms In The Insulin Receptor Family
Funder
National Health and Medical Research Council
Summary
The receptor molecules that we are studying are involved in two disease states, namely, diabetes and cancer. These diseases are particularly relevant in the context of Australia's aging population. The task of these particular receptor molecules is to pass messages from the outside of cells to the interior of cells. We are seeking to understand, at the molecular level of detail, the way in which these messages are transferred, with the potential to lead to new avenues for therapeutic development ....The receptor molecules that we are studying are involved in two disease states, namely, diabetes and cancer. These diseases are particularly relevant in the context of Australia's aging population. The task of these particular receptor molecules is to pass messages from the outside of cells to the interior of cells. We are seeking to understand, at the molecular level of detail, the way in which these messages are transferred, with the potential to lead to new avenues for therapeutic development in the context of these two diseases.Read moreRead less
Structural Characterisation Of The Co-inhibitory Complex Formed By The Tumour Suppressor PTEN And The Metastatic Factor PREX2
Funder
National Health and Medical Research Council
Funding Amount
$563,602.00
Summary
Metastasis is a major cause of cancer mortality. Characterisation of key proteins that regulate metastasis is therefore a priority. PTEN and PREX2 are enzymes that play key roles in metastasis in melanoma, and other cancers. We will determine the structural basis of PTEN:PREX2 co-inhibition, and determine how cancer-associated PREX2 mutations dysregulate this inhibitory complex. This study will provide the necessary knowledge for future drug development programs targeting PTEN:PREX2 in cancer.