Role Of Exported Proteins In Malaria Parasite Development In The Liver
Funder
National Health and Medical Research Council
Funding Amount
$520,613.00
Summary
Each year over 250 million people contract malaria and over 1 million die. The key to the malaria parasite’s success is the ability to live inside host cells, including hepatocytes and erythrocytes. Here, we aim to determine how the malaria parasite lives within hepatocytes, to engineer mutant parasites that can no longer do so and to assess whether mutant parasites confer protection against future malaria. Our program will use the most virulent human parasite P. falciparum and the rodent parasi ....Each year over 250 million people contract malaria and over 1 million die. The key to the malaria parasite’s success is the ability to live inside host cells, including hepatocytes and erythrocytes. Here, we aim to determine how the malaria parasite lives within hepatocytes, to engineer mutant parasites that can no longer do so and to assess whether mutant parasites confer protection against future malaria. Our program will use the most virulent human parasite P. falciparum and the rodent parasite P. berghei.Read moreRead less
Nuclear Transport In Health And Disease; Towards Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$851,980.00
Summary
This research fellowship will enable new therapeutic approaches to viral disease and cancer that target the transport process. I have already licenced an inhibitory molecule for Dengue virus which is progressing towards the clinic. I will now extend my research into a vibrant translational program of developing anti-viral (HIV, Respiratory Syncytical Virus, VEEV) as well as anti-cancer agents that will represent realistic therapeutic options in the near future.
Many bacterial pathogens invade host cells to replicate and avoid detection by the host. These pathogens interact with the host and by manipulating it to its benefit they establish an environment to survive in. A detailed understanding of the targeted hosts pathways and which are essential for pathogen survival is knowledge that will allow future development of therapeutic intervention strategies.
INHIBITORS OF DENGUE VIRUS NONSTRUCTURAL PROTEIN 5 NUCLEAR TRAFFICKING AS PROBES OF DENGUE BIOLOGY
Funder
National Health and Medical Research Council
Funding Amount
$741,136.00
Summary
Viral disease is one of the most significant health problems world-wide, making the identification of new therapeutics of critical importance. We aim to characterise in detail novel compounds which inhibit the interaction of the host cell with Dengue virus, and test them in a series of relevant infectious models for Dengue.
Function And Inhibition Of Plasmepsin V In Targeting Malaria Virulence Proteins Into Human Erythrocytes
Funder
National Health and Medical Research Council
Funding Amount
$407,845.00
Summary
Malaria parasites dramatically renovate infected erythrocytes to survive and evade the host immune system by delivering hundreds of exported parasite proteins into the cell. The parasite protease Plasmepsin V is essential for protein export. We aim to develop potent inhibitors of this protease in the hope of blocking its function and killing the parasite. We also aim to discover the components of the trafficking pathway after cleavage by Plasmepsin V that sorts virulence proteins to the host cel ....Malaria parasites dramatically renovate infected erythrocytes to survive and evade the host immune system by delivering hundreds of exported parasite proteins into the cell. The parasite protease Plasmepsin V is essential for protein export. We aim to develop potent inhibitors of this protease in the hope of blocking its function and killing the parasite. We also aim to discover the components of the trafficking pathway after cleavage by Plasmepsin V that sorts virulence proteins to the host cell.Read moreRead less
Unraveling The Dynamic Munc18a:Syntaxin1 Interaction Required For Neurotransmission
Funder
National Health and Medical Research Council
Funding Amount
$674,591.00
Summary
Membrane trafficking, the topic of the 2013 Nobel prize in Medicine, is required for delivery of cellular cargo. This research will investigate the interactions and structures of proteins from the neuronal membrane trafficking system. Understanding how this system operates will expand our knowledge of processes fundamental to learning and memory and may ultimately lead to development of selective therapeutics for treating a range of diseases.
Understanding the basic biology of cells will allow us to pinpoint key mechanisms and molecules that underpin multiple diseases and are targets for treatments. The broad aims of this research program include the development of new therapies for chronic inflammatory diseases, understanding how proteins are sorted and trafficked inside cells in processes that are essential to immunity and cancer biology, and identifying new intracellular targets to block bacterial invasion and infectious diseases.
Regulation Of Nucleocytoplasmic Transport; Role In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$823,008.00
Summary
Transport into and out of the nucleus is central to the function of the cells from complex organisms such as mammals. This research program aims to improve understanding of nuclear transport and its regulation in the context of infection by medically relevant viruses, as well as in the context of cancer, and normal cell growth/development. It will contribute to developing new anti-viral therapeutics/vaccines, drug delivery strategies for cancer, and understanding causes of male infertility.
Endosomal Sorting Of Amyloid Precursor Protein In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$858,643.00
Summary
Alzheimer's Disease is a progressive neurological disorder and is the most common cause of dementia. Effective treatments are desperately needed, but none are currently available. The toxic amyloid peptide A? is central to disease pathology and is derived from breakdown of the Alzheimer’s amyloid precursor protein (APP). In this project we will examine the interactions between APP and the molecular machinery that controls its location in the cell and subsequent degradation.
Subcellular Trafficking Of P Proteins Of Human Pathogenic Viruses: Roles In Viral Pathogenicity And Targeting For Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$578,352.00
Summary
In order to infect humans, pathogenic viruses such as rabies, Nipah, Hendra and Australian bat lyssavirus must be able to evade the immune response. To do this, viruses produce "interferon antagonists" that interfere with specific immune processes by mechanisms that are not fully understood. Our study will characterise the mechanisms used by rabies and other viruses to block immunity, and identify strategies to disable viral immune evasion, rendering these lethal viruses susceptible to destructi ....In order to infect humans, pathogenic viruses such as rabies, Nipah, Hendra and Australian bat lyssavirus must be able to evade the immune response. To do this, viruses produce "interferon antagonists" that interfere with specific immune processes by mechanisms that are not fully understood. Our study will characterise the mechanisms used by rabies and other viruses to block immunity, and identify strategies to disable viral immune evasion, rendering these lethal viruses susceptible to destruction by the human immune system.Read moreRead less