Dissecting The Contribution Of Malaria Translocon Components To Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$326,583.00
Summary
The malaria parasite exports hundreds of proteins into its host red blood cell via a unique protein export machinery. This enables the parasite to avoid immune detection, resulting in over one million deaths annually. This proposal will use a rodent malaria infection model to address the functional significance and contribution of the machinery to malaria disease to discern if it will provide a potential target for anti-malaria drugs.
Systematic And Sensitized Screens For Novel Genes That Regulate The Neural Differentiation Of Mouse Embryonic Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$360,634.00
Summary
Embryonic stem (ES) cells are cells in the embryo that can transform into any cell type. Genes that direct mouse ES cells to transform into cells of the nervous system will be uncovered by selecting a group of likely suspects, and disrupting the DNA sequences of these genes to see whether neural differentiation occurs normally in their absence. The effects of the gene disruptions will be examined in the developing neural system of the mouse embryo.
Somatic Gene Trapping In Schistosoma Mansoni _ The Key To Functional Analysis
Funder
National Health and Medical Research Council
Funding Amount
$623,270.00
Summary
Blood flukes are endemic in 76 countries and infect 300 million people worldwide. Control largely relies on the drug praziquantel. However, its wide scale use has led to concerns that drug resistance will develop. In this study we will use ñgene trap vectorsî to introduce insertional mutations into the schistosome genome. This will help to understand the function and importance of genes in biochemical pathways used by the parasite and to define effective targets for drug and vaccine development.
Identification Of Factors Critical For Maintenance Of The Epidermal Barrier
Funder
National Health and Medical Research Council
Funding Amount
$616,950.00
Summary
The human skin plays a crucial role in the body’s defence against our hostile environment. The outer most layer of the skin, the epidermis is the key structural component of the skin barrier and is essential for its integrity. We have identified a family of genes that are pivotal for epidermal barrier formation, maintenance and repair. This project examines the mechanisms that underpin the function of this family, and has broad ramifications in a host of dermatological conditions.
Personalised Medicine For Mitochondrial Disorders: Targeting Pathogenic Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$1,770,213.00
Summary
Mitochondria are our cellular power plants that burn sugars, fats and proteins to generate energy. Each week in Australia a child is born with a mitochondrial disorder. Many of these children die in the first years of life and most suffer from severe disease, particularly affecting their brain and/or heart. We will use stem cell models to better understand the basic biology of these disorders and to develop targeted therapies to improve the outcomes for affected patients.
The Role Of Accessory Subunits And Assembly Factors In The Biogenesis Of Respiratory Chain Complex I
Funder
National Health and Medical Research Council
Funding Amount
$569,987.00
Summary
The mitochondrial respiratory chain produces most of the energy required for our cells to grow and function. Complex I is the first enzyme of this chain and its defects are the most prevalent cause of mitochondrial disease, which often results in infant fatality. Defects in complex I have also been associated with Parkinson's disease and oxidative stress. This study will provide important new information into how complex I is built and what goes wrong to cause disease.
Characterising Complex I Function And Dysfunction In Mitochondrial Disease
Funder
National Health and Medical Research Council
Funding Amount
$316,449.00
Summary
The cells in our body produce energy in power plants called “mitochondria”. Mitochondrial disease affects 1 in 5000 live births. Currently there is no cure, but understanding how the genes mutated in mitochondrial disease work is an important step to finding one. Previous research relied on patient samples; however we will employ new technologies allowing us to rapidly model mitochondrial disease in a laboratory setting.
Functional Characterisation Of The Essential Aurora Kinase Family In The Human Malaria Parasite Plasmodium Falciparum
Funder
National Health and Medical Research Council
Funding Amount
$511,699.00
Summary
Malaria is responsible for 300 million new clinical cases and 650.000 deaths yearly. There is no vaccine and drug resistance is a growing problem. Protein kinases are key players in most cell functions and recognised potential drug targets. We will focus on the essential Plasmodium Aurora mitotic kinases, by localising them inside the parasite, identifying their binding partners and deciphering their in vivo function, to provide a strong biology basis for downstream drug discovery research.