Using Single-cell Genomics To Resolve Functional Diversification By CD4+ T Cells In Vivo
Funder
National Health and Medical Research Council
Funding Amount
$1,048,096.00
Summary
During immune responses, individual CD4+ T cells multiply and produce hundreds of descendants, with close relatives within a family often developing very different skills. How such differences emerge from one ancestor remains unclear. We use new methods to look at individual CD4+ T cells in unprecedented detail, allowing us to see how close relatives begin to grow apart. Using this, we hope to find novel ways of educating CD4+ T cells to prevent infectious and immune-mediated diseases.
Regulation Of Macrophage Function And Gene Expression By The Th2-Promoting Stimulus, ES-62
Funder
National Health and Medical Research Council
Funding Amount
$465,750.00
Summary
White blood cells are responsible for co-ordinating the immune response against foreign micro-organisms. Macrophages are a particular type of white blood cell that attempt to destroy microbes during the initial stages of an infection, but also release toxic substances that are responsible for pathology and side effects during many immune responses. This project aims to address how macrophages are involved in a particular type of immune response that develops when individuals are susceptible to c ....White blood cells are responsible for co-ordinating the immune response against foreign micro-organisms. Macrophages are a particular type of white blood cell that attempt to destroy microbes during the initial stages of an infection, but also release toxic substances that are responsible for pathology and side effects during many immune responses. This project aims to address how macrophages are involved in a particular type of immune response that develops when individuals are susceptible to certain diseases including asthma and diseases associated with intracellular infections. We are identifying genes expressed in macrophages during these immune responses that are likely to be involved in susceptibility to such diseases.Read moreRead less
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.
The Mezzanine T Cell Response: Intervening At The Coal Face
Funder
National Health and Medical Research Council
Funding Amount
$765,585.00
Summary
In an initial immune response, specialised cells in lymph nodes tell T cells to multiply; the stimulated T cells depart and enter target tissue (e.g. lung in the case of flu). We describe a new response whereby the target tissue itself can tell T cells to multiply further. This response in target tissues reveals a new way of altering immune responses. This is especially important as in many diseases, the primary lymph node response has already occurred, so cannot be therapeutically intervened.
The Role Of CD1-restricted T Cells In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$431,000.00
Summary
The human immune system requires T cells for survival. Specialised populations of T cells exist that patrol the body and target unwanted lipid molecules expressed by bacteria or by cells that have become abnormal or cancerous. I will identify these T cells in human blood and skin and determine their role in protection against disease. I will explore the types of lipids molecules recognised by these T cells and use this information to help prevent human diseases.
Defining The Coordination Of Immune Responses To Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$640,210.00
Summary
Understanding how immune responses are coordinated is critical for the design of new therapies and vaccines to target infectious diseases and cancers. This project will utilise advanced imaging combined with novel tools to dissect the complex interactions that occur between immune cells as they are activated and patrol the body to eliminate infectious pathogens.
The Role Of The Transcription Factor IRF4 In Peripheral Cd8 T Cell Differentiation
Funder
National Health and Medical Research Council
Funding Amount
$399,176.00
Summary
T cells protect against viral infections and fight cancer cells. In order to fulfill these roles T cells have to undergo significant phenotypic and functional changes. Our preliminary data indicate a central role for the regulator protein IRF4 in this process, as T cells that lack this protein are unable to grow and acquire the cellular tools necessary to provide protection. We wish to characterize the role of IRF4 in T cells in detail and aim to identify the processes regulated by IRF4.
Targeting Adenosine Mediated Immunosuppression To Enhance CAR T Cell Activity
Funder
National Health and Medical Research Council
Funding Amount
$633,447.00
Summary
The use of white blood cells genetically engineered to eradicate cancer cells specifically has been a major breakthrough in cancer treatment. These cells (CAR T cells) are very effective in blood cancers, but do not currently work well in other cancers. This is due to the immune suppressing nature of the cancer environment. I propose to use strategies to overcome this by genetically reprogramming the CAR T cells to be resistant to suppression by the cancer and therefore be more effective.
Genetic Modulation Of The Host Response To Pulmonary TB
Funder
National Health and Medical Research Council
Funding Amount
$540,273.00
Summary
Tuberculosis (TB) is an enormous global health problem. The World Health Organisation estimates that TB, which is caused by infection with the bacteria Mycobacterium tuberculosis, infects 2 billion individuals, leading to 2 million deaths and 8 million new cases of disease per year. Most TB disease is not manifest at the time of infection, but is a reactivation of latent disease in people who do not completely eradicate the primary infection. In a latent infection an effective chronic host respo ....Tuberculosis (TB) is an enormous global health problem. The World Health Organisation estimates that TB, which is caused by infection with the bacteria Mycobacterium tuberculosis, infects 2 billion individuals, leading to 2 million deaths and 8 million new cases of disease per year. Most TB disease is not manifest at the time of infection, but is a reactivation of latent disease in people who do not completely eradicate the primary infection. In a latent infection an effective chronic host response contains dormant TB organisms inside activated macrophages. Cells are recruited to wall off infected macrophages and specific T cells continually induce the activate state with minimal tissue damage (immunopathology). Although currently available antibiotics can kill TB organisms, the treatment is prolonged, expensive, difficult to administer in poorly resourced regions and not effective against multi-drug resistant organisms. New therapies to treat both active disease and prevent reactivation in individuals who are latently infected are urgently required. This proposal will address this problem using a novel approach, namely gene manipulation to augment host immunity to TB and limit concurrent immunopathology. We will construct vectors to increase expression of the key immune molecules, the T lymphocyte activating cytokines IL-12 and IL-23, and the macrophage effector molecules LRG-47 and Indoleamine 2,3-Dioxygenase (IDO). These molecules are known to be involved in TB killing. We will determine if increasing their expression increases the killing capacity of TB-infected macrophages and we will examine how these molecules interact to aid clearance of the TB bacilli. This internationally competitive grant will further our detailed understanding of the complex immune response to TB organisms and lead to the development of novel therapies to treat TB infection and prevent reactivation of latent disease.Read moreRead less
The Structure And Composition Of The T-cell Receptor-CD3 Complex
Funder
National Health and Medical Research Council
Funding Amount
$434,644.00
Summary
Our research will provide a fundamental advance in our understanding of how foreign viruses and pathogens trigger the immune system. Gaining a greater understanding of these central events will facilitate the design of novel therapies to treat immune associated disorders such as transplant rejection, autoimmune disease and some cancers.