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.
Mechanisms For Ageing Changes In The Hepatic Sinusoid
Funder
National Health and Medical Research Council
Funding Amount
$413,750.00
Summary
We recently discovered changes in the blood vessels of the liver that occur with old age that we have called pseudocapillarisation. These changes include thickening of the liver sinusoidal endothelium, deposition of basal lamina and collagen, and marked loss of specialized pores within the endothelium called fenestrations. These changes have profound effects on the transfer of many substrates including toxins, drugs, oxygen, hormones and lipids from the blood into the liver and thus may explain ....We recently discovered changes in the blood vessels of the liver that occur with old age that we have called pseudocapillarisation. These changes include thickening of the liver sinusoidal endothelium, deposition of basal lamina and collagen, and marked loss of specialized pores within the endothelium called fenestrations. These changes have profound effects on the transfer of many substrates including toxins, drugs, oxygen, hormones and lipids from the blood into the liver and thus may explain in part the fact that old age is the major risk factor for many diseases and adverse drug reactions. To further understand the mechanisms for these important ageing liver changes, we are proposing several studies. First, the effects of caloric restriction on the liver blood vessels will be studied because caloric restriction delays the primary ageing process. Second we will study the effects of ageing on F-actin, ATP, caveolin-1 and VEGF because these mechanisms have established roles in regulating the structure and function of the liver blood vessels and in particular their fenestrations. Finally we will determine whether VEGF can reverse the ageing changes in the liver blood vessels and stimulate the formation of new fenestrations within these blood vessels. Our research provides one mechanism for the inexorable association between old age and susceptibility to disease - based on primary ageing changes in the liver. As well as increasing our understanding of the cellular changes for ageing and the basic mechanisms involved in the regulation of the liver endothelial cells and their fenestrations, this proposed research will provide a foundation for the development of therapeutic interventions for the prevention and treatment of some age-related disorders.Read moreRead less
Life needs energy. We breathe and eat to make the universal biological fuel adenosine triphosphate (ATP). We turn over our own body weight in ATP every day and imbalances in this process lead to severe disorders such as obesity, diabetes and heart disease as well as to ageing. For any real breakthroughs we need to understand the machinery behind biological energy conversion in molecular detail and this is what my laboratory is aiming to achieve.
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.
Peripheral Membrane Proteins In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$640,210.00
Summary
Peripheral membrane proteins are critical for processes such as cell transport, signaling, neurosecretion and development. As such, their dysfunction can lead to many debilitating diseases including cancer, inflammation and neurodegeneration. This project will establish fundamental new knowledge about how peripheral membrane proteins regulate cell function, how their perturbation or mutation results in human disease, and will inform efforts to target them for future therapeutic outcomes.
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