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.
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.
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.
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
Autophagy: A New Pathway For Presenting Antigen In Dendritic Cells.
Funder
National Health and Medical Research Council
Funding Amount
$444,973.00
Summary
Microbes are chopped up and digested before being displayed to the immune system. Here we will investigate a new pathway termed _autophagy� that helps cells to digest material for immune display.
I am a cell biologist investigating the means by which intracellular compartmentalization of signalling proteins determines signalling outcomes and cell fate. I focus particularly on signals that regulate immune function and cancer progression.
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.
How membrane-sensing proteins regulate synaptic vesicle endocytosis. This project aims to elucidate the molecular basis of how membrane-sensing proteins regulate synaptic vesicle endocytosis in mammalian central neurons. Nerve cells’ ability to transmit cellular information to one another is important for normal brain function. Efficient communication between neurons through sustained neurotransmitter release relies on the continuous supply of synaptic vesicles in presynaptic nerve terminals. Ke ....How membrane-sensing proteins regulate synaptic vesicle endocytosis. This project aims to elucidate the molecular basis of how membrane-sensing proteins regulate synaptic vesicle endocytosis in mammalian central neurons. Nerve cells’ ability to transmit cellular information to one another is important for normal brain function. Efficient communication between neurons through sustained neurotransmitter release relies on the continuous supply of synaptic vesicles in presynaptic nerve terminals. Key to this process are membrane dynamics during synaptic vesicle retrieval, but the precise underlying mechanisms are not well understood. The intended outcome of this project is insights into the molecular mechanisms of synaptic transmission, the fundamental process of brain function, increasing understanding of physiological processes such as muscle movement, vision, hearing, touch, learning and memory.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE130100078
Funder
Australian Research Council
Funding Amount
$800,000.00
Summary
Live molecular imaging using super resolution microscopy, two photon and spinning disk confocal microscopy. With recent developments of super-resolution microscopy it is now feasible to image single molecules within the cellular environment in living cells. Such insight is key to understanding basic biological interactions that govern the wiring of our brain, communications between cells and neurons and cell-cell adhesion.
Nuclear functions of the microtubule-associated protein tau. The important neuronal protein, tau, has cellular functions that go far beyond its established role in stabilising microtubules. This project will determine which tau species are nuclearly localised, what the consequences are for nuclear functions, and how phosphorylation regulates this localisation.