I am an immunologist determining the development and function of the dendritic cell system, including its role in autoimmunity and resistance to infection.
Role Of Dendritic Cell Subsets In The Generation Of CD4 T Cell Memory
Funder
National Health and Medical Research Council
Funding Amount
$563,554.00
Summary
This project studies the mechanisms responsible for establishing immunologic memory that is generated by vaccination and determines its efficacy. We aim to identify and study previously unacknowledged factors that critically affect the efficacy of vaccination. The results will be significant for both preventative and therapeutic vaccination (cancer, autoimmunity) and will help us to design new vaccines to improve immune function in infection, autoimmunity and cancer.
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.
Identification Of Novel Regulators Of Flt3 Receptor-dependent Dendritic Cell Development And Differentiation
Funder
National Health and Medical Research Council
Funding Amount
$605,043.00
Summary
Dendritic cells are specialized immune cells that play a key role in regulating the immune system. In the resting animal, their differentiation is largely regulated by signalling though the Flt3 pathway - the pathway most frequently dysregulated in leukemias. This project will generate a a detailed map of the important signals that instruct dendritic cell development along the Flt3 pathway and provide improved understanding of the cellular and molecular controls of this pathway.
Herpes Simplex Virus Type 2 Modulates The HIV-1 Infection Of Plasmacytoid And Myeloid Dendritic Cells.
Funder
National Health and Medical Research Council
Funding Amount
$76,637.00
Summary
The aim of my project is to find out why people with herpes simplex virus are more susceptible to HIV infection. Herpes simplex is a common sexually transmitted disease and causes genital ulcers in both men and women. Understanding how the immune system responds to these two viruses will help to reduce heterosexual spread of HIV.
T cells are a central component of the immune system and without T cells the body is very vulnerable to infections. One subgroup of T cells is the killer T cells that are important for identifying and killing cells infected by viruses and bacteria. The immune system works to maintain T cell numbers at a fairly constant level and part of this process includes sending signals to the killer T cells from other cells via cell surface protein interactions and soluble mediators, such as cytokines. We h ....T cells are a central component of the immune system and without T cells the body is very vulnerable to infections. One subgroup of T cells is the killer T cells that are important for identifying and killing cells infected by viruses and bacteria. The immune system works to maintain T cell numbers at a fairly constant level and part of this process includes sending signals to the killer T cells from other cells via cell surface protein interactions and soluble mediators, such as cytokines. We have been studying killer T cells, which are missing a protein SOCS1. SOCS1 is important for switching off the signals generated by a group of cytokines. As a consequence of being unable to correctly regulate cytokine signals these killer T cells multiply inappropriately and contribute to disease development. Our current work is aimed at achieving a better understanding of the particular interactions between killer T cells and other immune system cells and the soluble factors that deliver important signals for maintaining killer T cells in the immune system. The ability to better understand the factors controlling the maintenance of killer T cells will enable us to more intelligently target the immune system ,which is important for improving vaccine strategies and cancer immunotherapy as well as for controlling T cells that are activated inappropriately, such as in autoimmune disease.Read moreRead less
Investigation Into The Immunogenicity Of Dendritic Cell-derived Exosomes
Funder
National Health and Medical Research Council
Funding Amount
$257,036.00
Summary
Dendritic cells are essential in immune responses. They have unique capacity to stimulate lymphocytes specific to viruses, bacteria and cancers. They are extremely rare and difficult to isolate. We have developed a method of culture which gives a continuous supply of dendritic cells. Cells produced in our culture also produce a high yield of acellular membranous particles called 'exosomes' which have been previously been very difficult to isolate and characterise. Some preliminary reports sugges ....Dendritic cells are essential in immune responses. They have unique capacity to stimulate lymphocytes specific to viruses, bacteria and cancers. They are extremely rare and difficult to isolate. We have developed a method of culture which gives a continuous supply of dendritic cells. Cells produced in our culture also produce a high yield of acellular membranous particles called 'exosomes' which have been previously been very difficult to isolate and characterise. Some preliminary reports suggest that exosomes can induce or modify immune responses and that they have enormous immunotherapeutic potential. Further study of their clinical application is limited by the difficulty of isolating enough dendritic cells from which to isolate exosomes. This study will involve production and characterisation of exosomes from our unique murine dendritic cell culture system. Exosomes isolated will be assessed in terms of potential for immunotherapeutic treatment of disease such as cancer, viral infection and autoimmunity.Read moreRead less
Defining The Role Of Tumour Necrosis Factor Apoptosis Inducing Ligand (TRAIL) In Experimental Visceral Leishmaniasis.
Funder
National Health and Medical Research Council
Funding Amount
$153,250.00
Summary
The activation of pathogen-specific T cells by dendritic cells (DC) is a critical step in the control of most infections, as well as the success of many vaccine strategies. The specific cells and molecules involved in this process are still poorly defined. In this project, we will investigate the effects of a cell surface molecule called tumour necrosis factor related apoptosis inducing ligand (TRAIL) on the ability of DC to activate T cells during a parasitic infection caused by Leishmania dono ....The activation of pathogen-specific T cells by dendritic cells (DC) is a critical step in the control of most infections, as well as the success of many vaccine strategies. The specific cells and molecules involved in this process are still poorly defined. In this project, we will investigate the effects of a cell surface molecule called tumour necrosis factor related apoptosis inducing ligand (TRAIL) on the ability of DC to activate T cells during a parasitic infection caused by Leishmania donovani. By identifying the cells that express TRAIL and the effect that this molecule has on the development of immunity to pathogens, we will better understand the factors required to generate effective immune responses against infectious agents, and hence, develop better vaccines.Read moreRead less
Functional Suicide Of Selected Dendritic Cells By Cytochrome C: An In Vivo Model Lacking Cross-presentation
Funder
National Health and Medical Research Council
Funding Amount
$597,476.00
Summary
Certain white blood cells (dendritic cells) activate the immune system, especially its T cells. Infection of such cells elicits killer T cell responses. However not all infections infect dendritic cells. In such cases, the infectious material is eaten by dendritic cells and moved to certain areas within the cell. This process is called cross-presentation and how important it is during various diseases remains moot. We now have a model of testing this by eliminating these cross-presenting cells.