The aim of this project is to develop mathematical models and computer software capable of predicting immune responses to infection and disease. This “artificial immune system” should lead to improved vaccine design and better understanding of what causes the immune system to attack its own body, causing autoimmune disease, or fail to respond, causing immunodeficiency. This enabling science could then lead to improvements in treatment for a range of conditions of clinical importance.
Investigation Of Dendritic Cell Activation And Function In A Murine Model Of Plasmodium And Schistosoma Co-infection
Funder
National Health and Medical Research Council
Funding Amount
$358,938.00
Summary
Malaria is responsible for over 2 million deaths annually, mainly in sub-Saharan Africa. Importantly, around 1 billion people in malaria endemic areas are infected with parasitic worms, thus malaria and worm co-infections frequently occur. This project will investigate how malaria and worm parasites interact to influence the immune response and clinical outcomes of each other in a mouse infection model. This will provide new strategies for the design of effective treatments in co-endemic areas.
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.
Cutaneous Inflammation, Bone Marrow Dendritic Cells, And Implications For Immune Responses And Immune Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$327,151.00
Summary
With inflammation of the skin due to excessive sun exposure or chemicals, biological signals are sent to the bone marrow where immune fighting cells are generated. However, the immune system must not overreact. We have measured bone marrow derived immune cells with reduced function following skin inflammation which we propose is part of homeostasis. We need to better understand how these cells are altered and for how long they are altered.
Novel Vaccine Formulation For Immunotherapy Of Adenocarcinomas
Funder
National Health and Medical Research Council
Funding Amount
$178,400.00
Summary
We have designed a vaccine based on a unique delivery system. Mice immunised with vaccine were protected from a tumour challenge. We will now design a vacine with a cancer associated protein so that people once immunised can make killer cells. Since humans have different genetic makeup we will produce a vacine which is more effective and will benefit everyone. This vaccine will be more effective than a current vacine in that has yielded promising results in humans.
T cells play a central role in the immune response. The primary event in T cell activation is the triggering of a specific T cell receptor (TCR). Our studies will examine whether the protein TCPTP antagonises TCR-instigated T cell responses. Our studies may provide important new insights into alternative approaches for manipulating T cell-mediated immune responses in diseased states.
Investigation Of The Roles Of TNFa-related Apoptosis-inducing Ligand, TRAIL, In The Immune System.
Funder
National Health and Medical Research Council
Funding Amount
$436,980.00
Summary
TRAIL, is a newly described member of the tumour necrosis factor (TNF)-family of cytokines, which can kill a wide range of tumour cells, and virus infected cells, but not most normal cells. TRAIL has proven to be safe when administered to normal, tumour bearing, and virally-infected mice, and causes no detectable side-effects in these animals. As such it holds huge potential and is being widely investigated for use as a new anti-cancer therapy. Despite these findings, little is known about the t ....TRAIL, is a newly described member of the tumour necrosis factor (TNF)-family of cytokines, which can kill a wide range of tumour cells, and virus infected cells, but not most normal cells. TRAIL has proven to be safe when administered to normal, tumour bearing, and virally-infected mice, and causes no detectable side-effects in these animals. As such it holds huge potential and is being widely investigated for use as a new anti-cancer therapy. Despite these findings, little is known about the true physiological role of TRAIL in vivo. To define the normal roles of TRAIL, CIA has been characterising TRAIL gene knock-out mice. These studies have confirmed that TRAIL contributes to control of tumours in vivo, and in early events during anti-viral responses. However, these studies have also revealed novel roles for TRAIL in T cell biology, and B cell memory. Understanding how TRAIL contributes to these processes, will shed significant light on the potential of TRAIL to be used as a therapeutic agent for humans with lymphoproliferative disease, for illiciting better long-lived antibody responses such as after vaccination, and as an anti-viral reagent in immunocompromised individuals during virus infection.Read moreRead less
Induction Of Natural T-Regulatory Cells By Thymic Dendritic Cell Populations
Funder
National Health and Medical Research Council
Funding Amount
$413,775.00
Summary
In this study, we will determine the roles of the antigen presenting cells, namely denderitic cells, in the induction of T-regulatory cell (T-reg) developemnt in the thymus. T-reg cells play important roles in controlling the development of autoimmunity. This study will help to understand the possible causes of autoimmune diseases and to develop new treatments for these diseases.
Tolerance Induction By Antigen-presenting Cell-targeted Antigen
Funder
National Health and Medical Research Council
Funding Amount
$420,872.00
Summary
We have found that by ‘targeting’ antigen to the cells that ‘train’ the immune system we have been able to prevent the development of autoimmune disease. In the research proposed here we aim to develop new ways in which antigens can be targeted to these cells so that this approach can be applied clinically. The proposed studies will also determine how antigens targeted in this way restore self-tolerance and prevent autoimmune disease.