The Cell Biology Of Macropinocytosis Pathways In Antigen Presenting Cells
Funder
National Health and Medical Research Council
Funding Amount
$545,216.00
Summary
Cells internalise molecules in membrane-bound vesicles, a process known as endocytosis. This internalisation pathway is essential for many biological events, including the ability to capture foreign antigens and mount an effective immune response. Some internalisation pathways can be switched on by signals received at the cell surface. This study will identify the molecules that control antigen capture in immune cells. This knowledge is important for the development of better vaccines.
Identifying Molecular Machinery In Dendritic Cells.
Funder
National Health and Medical Research Council
Funding Amount
$687,500.00
Summary
Vaccines invoke immune responses that will protect a vaccinated host if they encounter infection. Vaccines can also be deployed to fight cancer. 'Dendritic cells' are the key immune cell responsible for vaccine immunity. While dendritic cells are pivotal to initiating vaccination, little is known about their internal machinery. This research proposal will identify new machinery for dendritic cell vaccine immunity that will serve as therapeutic targets to boost vaccination.
Generating Tumour-Specific Dendritic Cells For Cancer Therapy
Funder
National Health and Medical Research Council
Funding Amount
$288,210.00
Summary
Therapies using the immune system are showing promise for cancer treatment, particularly for melanoma, but complete durable responses are few and improvements are needed. We believe that such immunotherapies, in their current form, fail to sufficiently mimic a natural immune reaction to disease, and therefore fall short of effectively controling cancer. In particular, an alarm (danger signal) is not produced within tumour as it would be when the body is challenged by infectious agents. Such dang ....Therapies using the immune system are showing promise for cancer treatment, particularly for melanoma, but complete durable responses are few and improvements are needed. We believe that such immunotherapies, in their current form, fail to sufficiently mimic a natural immune reaction to disease, and therefore fall short of effectively controling cancer. In particular, an alarm (danger signal) is not produced within tumour as it would be when the body is challenged by infectious agents. Such danger signals are critical for the immune system to respond effectively and for white blood cells of the immune system to find their way to the disease organism and eliminate it. The strongest danger signals are produced by a type of white blood cell known as a dendritic cell (DC). These cells detect infectious agents and produce biochemical alarm molecules that alert the entire immune system to the danger resulting in powerful action against the disease. However, tumours are really just a part of our own body and no danger signal is produced. It is our aim to use genetic modification to make DC see tumours as a threat and produce danger signals. These gene-modified DC either alone, or in combination with other immunotherapies, may lead to destruction of tumours.Read moreRead less
Mechanisms Of Dendritic Cell-induced T-cell Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$314,773.00
Summary
Autoimmune diseases constitute a significant medical problem in the developed world and are increasing in incidence. Many control mechanisms exist in the body, but in people with genetic suceptibility to autoimmune disease, the mechanisms fail and the body's immune sytem attacks normal tissues or organs. We have developed a new approach to using the cells which train the immune system to re-educate the cells that would otherwise attack normal healthy tissues in autoimmune-prone individuals. Thes ....Autoimmune diseases constitute a significant medical problem in the developed world and are increasing in incidence. Many control mechanisms exist in the body, but in people with genetic suceptibility to autoimmune disease, the mechanisms fail and the body's immune sytem attacks normal tissues or organs. We have developed a new approach to using the cells which train the immune system to re-educate the cells that would otherwise attack normal healthy tissues in autoimmune-prone individuals. These cells (dendritic cells) are genetically modified to express the molecular targets of the autoimmune response. This in turn switches off the response to these targets. In this project we will explore how these cells can be used to turn off cells of the immune system and if cells of the immune system in turn control the dendritic cell's ability to do this.Read moreRead less
Dendritic cells are a very rare type of white blood cell which play a critical role in the initiation of the immune response. They are of particular interest to scientists interested in vaccination, as for a vaccine to work effectively, the vaccine must be presented to the rest of the immune system by the dendritic cell. It has only recently become apparent that there are several types of dendritic cell, and these different types of dendritic cell vary in their ability to present a vaccine to th ....Dendritic cells are a very rare type of white blood cell which play a critical role in the initiation of the immune response. They are of particular interest to scientists interested in vaccination, as for a vaccine to work effectively, the vaccine must be presented to the rest of the immune system by the dendritic cell. It has only recently become apparent that there are several types of dendritic cell, and these different types of dendritic cell vary in their ability to present a vaccine to the immune system. We have already identified some proteins that are expressed on the surface of only one type of dendritic cell. We will explore the possible use of these proteins as a means of delivering a vaccine to only one type of dendritic cell. This project will also identify new genes that are expressed in some types of dendritic cells but not others. These new genes whose expression does differ amongst the dendritic cells are potential targets for manipulating the immune system and ensuring more efficient vaccination.Read moreRead less
The Role Of The Dendritic Cell Surface Molecule Clec9A In Dendritic Cell Subset Function And Dead Cell Recognition
Funder
National Health and Medical Research Council
Funding Amount
$526,878.00
Summary
Dendritic cells (DC) are sentinels of the immune system. DC monitor the environment and regulate tolerance to self versus immunity to dangerous material. Different types of DC perform different jobs. We have identified a new surface molecule, Clec9A, on some mouse and human DC. We will investigate the function of Clec9A in the immune response. We will also use Clec9A to help unite mouse and human DC biology, since until now there have been few useful marker molecules common to both species.