Characterising And Visualising Cross-presenting Dendritic Cells Following Cutaneous Vaccinia Infection
Funder
National Health and Medical Research Council
Funding Amount
$415,682.00
Summary
Live imaging of cells within lymphoid organs provides a valuable tool allowing insight into how immune responses are initiated. Utilising novel reagents we will visualise and define these events following cutaneous infection with vaccinia virus.
Regulation Of Metabolic Dysfunction And Exhaustion Of Virus-specific T Cells During Chronic Infection
Funder
National Health and Medical Research Council
Funding Amount
$749,152.00
Summary
T cells control infections and cancer cells. During chronic infection or tumor development, however, loss of function of T cells prevents efficient clearing of pathogens or cancer cells, a phenomenon termed T cell ‘exhaustion’. We have found that the regulator protein IRF4 controls cellular nutrient usage, growth and function of T cells and that very amounts of IRF4 occur in T cells during chronic infection. We propose to examine the precise role of IRF4 in chronically stimulated T cells.
Identifying The Mechanism And Spectrum Of Activity Of The Antiviral Protein IFITM3
Funder
National Health and Medical Research Council
Funding Amount
$507,200.00
Summary
In response to an infection cells within the body are capable of expressing a range of molecules that help them resist infection, one such molecule is interferon induced transmembrane protein 3 (IFITM3). This recently identified but poorly studied potent antiviral protein dramatically influences the course of influenza infection in both mice and humans. We will explore the mechanisms of antiviral activity of IFITM3 and determine factors important in initiating and retaining expression.
Defining The Roles Of The Chemotactic Receptor EBI2 For The Regulation Of Leukocyte Migration And The Generation Of Immunity
Funder
National Health and Medical Research Council
Funding Amount
$421,747.00
Summary
The proposed study aims at improving our understanding of the role of the immune cell receptor Epstein-Barr virus-induced gene 2 (EBI2) in guiding the movement of white blood cells during immune responses. The project will investigate the function of EBI2 in the control of infectious diseases and its regulation on human immune cells. These insights have the potential to create new therapeutic approaches to treat human autoimmune and inflammatory diseases and improve vaccine design.
Vaccines that deposit memory T cells within the lung, gut and genital tract hold enormous therapeutic potential, as these mucosal surfaces are major portals of entry into the body for many viruses. However, the accumulation of large numbers of T cells within the mucosal tissue may increase the number of target cells for T cell trophic viruses (eg HIV) to infect. We will explore factors that result in the generation of mucosal memory T cells that are resistant to virus infection.
Long Lived, Virus Resistant Resident Memory T Cells
Funder
National Health and Medical Research Council
Funding Amount
$415,218.00
Summary
Vaccines that deposit memory T cells within the lung, gut and genital tract hold enormous therapeutic potential, as these mucosal surfaces are major portals of entry into the body for many viruses. However, the accumulation of large numbers of T cells within the mucosal tissue may increase the number of target cells for T cell trophic viruses (eg HIV) to infect. We will explore factors that are important in the generation of mucosal memory T cells that are also resistant to virus infection.
Transcriptional Control Of Peripheral T Cell Differentiation During Pathogen Infection And Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$92,314.00
Summary
White blood cells, specifically helper and killer T cells, play an important role in fighting infection. They are tightly regulated and if not properly controlled can lead to aggressive autoimmune diseases such as diabetes and multiple sclerosis. My studies will elucidate the mechanisms behind the regulation of T cells at steady-state and during disease. Insights gained from this project will have implications for the design of new approaches to combat infectious and autoimmune diseases.
Subset Determination Of Tissue-Resident T Cell Memory
Funder
National Health and Medical Research Council
Funding Amount
$473,394.00
Summary
Immunity relies on white blood cells called T cells that circulate around the body and which are also found permanently lodged at body surfaces. It is non-circulating T cells that are the most important in protecting against infection. In this application we propose to show that only a subset of T cells can form the resident population and to identify the molecules that determine T cell residency. This information can then be used for the efficient construction of disease preventing vaccines.
The body’s surfaces are continually under threat from microbes that may cause debilitating disease. Our ability to control such infections relies on our immune system, consisting of different cell types with specialised functions. We will study frontline immune cells that populate barrier tissues such as skin and mucosa where they provide enhanced local protection by responding vigorously on infection. Our studies will guide the development of future therapies harnessing our immune system.
Regulation Of T Cell Effector Function In Peripheral Tissues
Funder
National Health and Medical Research Council
Funding Amount
$698,550.00
Summary
Protection from infections relies on different types of immune cells. While some of these cells are found in the blood, others reside in peripheral tissues such as the skin. We will analyse the function of these peripheral immune cells to understand how they work to fight off infections. We will also investigate how so-called memory cells that permanently reside in peripheral tissues can protect from re-infection with similar bacteria or viruses.