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.
Autoimmune-based thrombocytopenia can be a life-threatening adverse event associated with viral load, surgery, drug therapies or the use of the anticoagulant, heparin. This grant will define mechanisms of anti-platelet antibody-dependent platelet activation and assess shedding of platelet-specific glycoprotein (GP)VI as an immediate consequence of this activation, provide a new strategy for evaluating risk of thrombosis in HIT.
A Novel Molecular Mechanism Controlling Myelopoiesis
Funder
National Health and Medical Research Council
Funding Amount
$878,439.00
Summary
The immune system is comprised of many different cell types, each with a specialised function. Many are short-lived and must be continually replenished throughout life. Abnormalities in this process underlie many human diseases, including immunodeficiency, autoimmunity and cancer. We have discovered a novel molecular mechanism that is critical for the production of immune cells. This project will investigate how this mechanism is controlled and the impacts on myelodysplastic syndromes.
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.
Dendritic cells are essential components of our immune systems. They are located throughout our body and provide the first line of defence against invading microbes. Dendritic cells sense the invader and send out signals to recruit our immune cells to the site of infection. Our research aims to understand how our dendritic cell network is set up and how it functions to promote our immune health.
A specialised set of T lymphocytes called Mucosal Associated Invariant T (MAIT) cells react against bacteria and yeast, and reside at mucosal sites where the body's immune defences are most easily breached, e.g. respiratory tract and intestinal mucosa. This study investigates the role of MAIT cells in both protection and pathology in bacterial infections. Controlling MAIT cells could help in treating these conditions.
Antigen-presenting cells control immune responses. Different types of these cells do different jobs and affect different diseases. We wish to control these processes by determining how the cells live and die. In particular we are interested in controlling the local immune responses during rejection of islet transplantation, which can cure type 1 diabetes.
Innate Immune Signalling In Mycobacterium Tuberculosis Infection
Funder
National Health and Medical Research Council
Funding Amount
$562,857.00
Summary
Tuberculosis (TB) is a major global health threat that causes 1.5 million deaths every year. This study will characterise a new molecular control mechanism that optimises the immune response to the bacteria that cause TB and determine how it contributes to controlling the infection. Such knowledge is essential to help improve patient management and develop better treatments for this devastating disease.
Defining The Interaction Of HIV With The Interferon System In Initial Mucosal Infection
Funder
National Health and Medical Research Council
Funding Amount
$867,716.00
Summary
Very early after virus exposure, immune cells secrete interferons that help limit the spread of viruses within the body. We will investigate the complex interplay between HIV and the interferon system, especially how HIV inhibits the early induction of interferon to aid its spread and then how the body later restores the interferon response. We will also examine how HIV manipulates the interferon system in order to persistent latent reservoirs within tissues.
Antigen Presentation, Recognition And The Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$14,927,045.00
Summary
This program focuses on understanding the development of immunity during infection or inflammatory diseases using a broad array of techniques to dissect the function of various immune cell types and to explore the relationship between structure and function of important cell surface molecules. These studies will improve our ability to design new generation vaccines for combating infectious diseases, controlling cancer, or limiting autoimmune or inflammatory diseases.