Developing A New Strategy For Treating Demyelinating Peripheral Diseases
Funder
National Health and Medical Research Council
Funding Amount
$496,250.00
Summary
Incomplete remyelination is a significant component of the persistent clinical disability of peripheral demyelinating neuropathy, contributing to conduction deficits and the secondary axonal damage. A crucial therapeutic challenge is to identify ways to promote remyelination. This project aims to develop a new strategy and a novel clinically relevant target for treating peripheral demyelinating neuropathy.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE110100092
Funder
Australian Research Council
Funding Amount
$300,000.00
Summary
Fluorescence microscopy with optical tweezers: imaging cellular responses. Life relies on the ability of our cells to receive and respond to signals with pinpoint accuracy, involving both chemical and mechanical signals. This equipment will allow scientists to expose cells to both types of signals and measure the response at an unprecedented level of accuracy for the first time.
Regulation of lung immune-epithelial networks sensing environmental change. This study aims to uncover how lung epithelial cells engage with immune cells and determine their cellular and molecular wiring to ensure homeostatic maintenance and essential repair processes of lung tissues. Maintenance of lung epithelial-immune networks is essential to maintain normal lung tissue structure and function, and to induce immune responses to protect against microbial challenges or inhaled potentially toxic ....Regulation of lung immune-epithelial networks sensing environmental change. This study aims to uncover how lung epithelial cells engage with immune cells and determine their cellular and molecular wiring to ensure homeostatic maintenance and essential repair processes of lung tissues. Maintenance of lung epithelial-immune networks is essential to maintain normal lung tissue structure and function, and to induce immune responses to protect against microbial challenges or inhaled potentially toxic substances. Understanding this molecular program of epithelial-immune cell-mediated sensing/repair will be essential to understand how tissue-repair processes can be driven in the lung, an organ critical for respiration and thus life.Read moreRead less
Understanding the T cell repertoire in health and disease. Immune recognition of viruses usually involves a large number of different 'killer T cells' that kill cells infected by virus. However, during prolonged infection or in the elderly the number of different killer T cells that recognise the virus is greatly reduced. This reduction in the diversity of the immune response allows the virus to avoid immune recognition, and leads to more severe infection. We aim to understand how diversity is ....Understanding the T cell repertoire in health and disease. Immune recognition of viruses usually involves a large number of different 'killer T cells' that kill cells infected by virus. However, during prolonged infection or in the elderly the number of different killer T cells that recognise the virus is greatly reduced. This reduction in the diversity of the immune response allows the virus to avoid immune recognition, and leads to more severe infection. We aim to understand how diversity is generated in the immune response, and how it becomes narrowed with age or prolonged infection. This information can be used to design vaccines for persistent infections such as HIV, and to improve immune control of infection in the elderly.Read moreRead less
Signalling Networks As Targets For Antibody Therapy In Glioma.
Funder
National Health and Medical Research Council
Funding Amount
$526,683.00
Summary
Antibodies are a major component of the bodies immune system that bind (i.e. stick) to foreign substances such as viruses. Once bound, these antibodies can activate other parts of the immune system, which help destroy the foreign substance. Analogous to the situation above, a number of institutions are testing antibodies that bind to cancer cells, in order to determine if they are able to destroy these cells. It is also possible to generate antibodies that bind to receptors on the surface of can ....Antibodies are a major component of the bodies immune system that bind (i.e. stick) to foreign substances such as viruses. Once bound, these antibodies can activate other parts of the immune system, which help destroy the foreign substance. Analogous to the situation above, a number of institutions are testing antibodies that bind to cancer cells, in order to determine if they are able to destroy these cells. It is also possible to generate antibodies that bind to receptors on the surface of cancer cells and block their function. If you target a receptor critical to the growth or survival of a cancer cell in this way, then swtiching-off this signal may inhibit tumor growth. In this proposal we plan to test a panel antibodies that recognize receptors important to the growth of brain cancer. Two of these antibodies have been generated and the other two will be made as part of this proposal. A key aspect of this proposal will be testing these antibodies in combination to determine how many receptors need to be targeted in order to get complete tumor regressions in animal models. Overall this work will help us identify new therapeutic strategies for the treatment of brain cancer. Finally, we will also analyze the way different receptors interact together in brain cancer cells.Read moreRead less
The macrophage nucleus - its form and function during migration in vivo. As cells migrate through tissues, they encounter complex, 3-dimensional environments that provide cues to guide them and present obstacles in their path. This project focuses on macrophages, a large immune cell capable of both amoeboid and mesenchymal modes of migration. The nucleus is the largest organelle and its bulk and stiffness must be managed as migrating cells travel through constrictions. The project uses specialis ....The macrophage nucleus - its form and function during migration in vivo. As cells migrate through tissues, they encounter complex, 3-dimensional environments that provide cues to guide them and present obstacles in their path. This project focuses on macrophages, a large immune cell capable of both amoeboid and mesenchymal modes of migration. The nucleus is the largest organelle and its bulk and stiffness must be managed as migrating cells travel through constrictions. The project uses specialised high-end microscopy and genetic methods to examine how the nucleus of migrating zebrafish macrophages deforms, repositions and is restructured during migration in living tissues, and how this influences macrophage locomotion. The goal is to provide fundamental insights into the cell biology of macrophage migration.Read moreRead less
Nuclear plasticity during neutrophil migration and function. This project aims to discover how nuclear shape affects neutrophil function. Cell migration needs overall cellular plasticity and plasticity of internal structures such as the nucleus. The neutrophil, one of the most peripatetic cell types, has a specialised lobulated nucleus, thought to facilitate its mobility and function. Using zebrafish reporter lines that concurrently display the nucleus and cytoplasm, this project will display th ....Nuclear plasticity during neutrophil migration and function. This project aims to discover how nuclear shape affects neutrophil function. Cell migration needs overall cellular plasticity and plasticity of internal structures such as the nucleus. The neutrophil, one of the most peripatetic cell types, has a specialised lobulated nucleus, thought to facilitate its mobility and function. Using zebrafish reporter lines that concurrently display the nucleus and cytoplasm, this project will display the dynamic plasticity of neutrophil nuclei during neutrophil migration and function in vivo. This project seeks to use the spatiotemporal resolution of a lattice light sheet microscope to examine this further, and explore its effect on neutrophil function. The project seeks to establish morphological and mechanical principles applying not just to neutrophils, but to all migratory cell types.Read moreRead less