NDI1 Therapy For NADH-Ubiquinone Oxidoreductase Deficiency
Funder
National Health and Medical Research Council
Funding Amount
$575,762.00
Summary
This study will test a new protein therapy that can act as a surrogate for a deficient or defective enzyme called Mitochondrial Complex 1. The deficiency occurs in newborns with defective genes for the proteins that form the enzyme. The defect causes metabolic malfunction in most organs, with patients needing specialist hospital and parental care, but there is no cure yet. We have successfully tested this in the lab but will now test this in our new animal model of the disease.
Mechanisms Of A Novel Strategy For Neuroprotection In Experimental Models Of Stroke And Epilepsy
Funder
National Health and Medical Research Council
Funding Amount
$480,499.00
Summary
Stroke and epilepsy are among the most common neurological disorders affecting many Australians. In both disorders, brain metabolism is disturbed. Dr. Borges has found that an edible oil inhibits seizures in mice and it is now being tested in epilepsy patients. This grant will allow her laboratory to study the effects of this oil against stroke and to investigate how it protects the brain. New knowledge obtained will help to develop new treatments for brain disorders.
Correlative Structure-function Studies Of Cis- And Trans-Golgi Membrane Traffic In Mammalian Cells
Funder
National Health and Medical Research Council
Funding Amount
$649,531.00
Summary
This project combines imaging by light and electron microscopy with additional techniques for studying protein function at the molecular level, to elucidate how changes in the 3D organisation of cellular machinery can lead to fundamental changes in the function and health of mammalian cells. Although this work includes detailed investigation of the 'insulin factory', it has the potential to modify established concepts on membrane traffic and protein secretion well beyond the field of diabetes.
Flaviviruses Must Come Of Age: Design Of Stable, Mature Particles By Structural Vaccinology
Funder
National Health and Medical Research Council
Funding Amount
$1,149,487.00
Summary
We have established a powerful toolset combining advanced structural biology and rapid virus engineering that allows us investigate the assembly of flaviviruses in novel ways. This project will integrate these approaches to investigate the role of new ligands that we have identified in the structure of medically-relevant flaviviruses including dengue virus and delineate a novel maturation path for flaviviruses, which will be used to design safer and more effective flavivirus vaccines.
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.
Structure And Mechanism Of Activation Of The Mechanosensitive Ion Channel TACAN
Funder
National Health and Medical Research Council
Funding Amount
$997,537.00
Summary
We propose to determine the structure and mechanism of activation of TACAN, a recently identified ion channel that defines a novel and uncharacterised class of channels. TACAN is specifically involved in sensing mechanical pain and contributes to mechanosensitive currents in the pain-receptor type of neurons. Our studies will increase knowledge of this novel class of proteins that will allow for the future development of treatments for several chronic pain conditions including arthritis.
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.