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.
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
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.
Structural And Functional Characterisation Of The Oncogene P-Rex1
Funder
National Health and Medical Research Council
Funding Amount
$623,447.00
Summary
The spread of cancer to other parts of the body (metastasis) is a major cause of mortality. The characterisation of proteins that regulate metastasis is therefore a priority. P-Rex1 plays a crucial role in promoting metastasis in breast and other cancers. We will determine the structural basis of P-Rex1 activity, and investigate how its dysregulation promotes aberrant cell growth. This study will provide the knowledge to build future drug development programs targeting P-Rex1 in cancer.
The Structural Basis For Promiscuity Of Drug Binding To HERG K+ Channels
Funder
National Health and Medical Research Council
Funding Amount
$713,035.00
Summary
Special proteins called ion channels control the electrical activity of the heart. Drugs that block ion channels can have the unwanted side-effect of altering the rhythm of the heart beat and causing sudden cardiac death. Extensive efforts are made to screen for this problem during drug development but it is still an inexact science. Here we will use high resolution imaging technologies to get a better understanding of how drugs bind to ion channel proteins.
Endosomal Protein Trafficking Complexes - Therapeutic Targets For Novel Antivirals
Funder
National Health and Medical Research Council
Funding Amount
$543,727.00
Summary
The enzyme Vps4 is a key target for the development of new antiviral drugs targeting a family of enveloped viruses that includes HIV (17,000 cases), Hepatitis B and C (420,000 cases) and Herpes Simplex (type I, II - 1.3 million cases). This project will use high resolution microscopy to investigate the molecular structures that enable infection by these and other Vps4-dependent enveloped viruses.
Targeting NDM-producing ‘superbugs’: Optimising Novel Combinations With ‘old’ Polymyxins Using Pharmacological, Molecular Imaging And Systems Biology Approaches
Funder
National Health and Medical Research Council
Funding Amount
$582,732.00
Summary
Rapid global spread of so-called NDM-producing bacterial ‘superbugs’ is presenting a major medical challenge. Without new antibiotics under development, polymyxin is becoming the only effective antibiotic. Unfortunately we recently revealed that treatment with polymyxin alone can rapidly lead to resistance in NDM-producing ‘superbugs’. This project will employ new tools to optimise rational polymyxin combinations, thereby providing urgently needed information to clinicians for treating these ver ....Rapid global spread of so-called NDM-producing bacterial ‘superbugs’ is presenting a major medical challenge. Without new antibiotics under development, polymyxin is becoming the only effective antibiotic. Unfortunately we recently revealed that treatment with polymyxin alone can rapidly lead to resistance in NDM-producing ‘superbugs’. This project will employ new tools to optimise rational polymyxin combinations, thereby providing urgently needed information to clinicians for treating these very problematic infections.Read moreRead less