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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.
Uncovering The Basis Of Inflammatory And Immunodeficiency Diseases
Funder
National Health and Medical Research Council
Funding Amount
$15,718,075.00
Summary
A world-class team from 3 institutions, spanning disciplines of clinical and experimental immunology, therapeutics, signalling and genetics, will identify how immune and inflammatory responses are controlled in both health and disease. The major outcomes of this work will be the generation of new knowledge, concepts and approaches to diagnose, prevent and treat the major human health problems of autoimmune diseases, inflammation, allergy and immunodeficiency.
It is feasible to sequence patient genomes but we need to know more about how genetic variants cause complex disease. We have sequenced genomes from patients with immune deficiency and will test the idea that genetic variation causes consistent changes in particular white blood cells, thus providing a bridge between genomic information and clinical diagnosis. Outcomes will include more accurate diagnosis, better understanding of immunity, and a strategy for using whole genome information.
Investigating B Cell Development, Maintenance And High-affinity Antibody Production By ENU Mutagenesis
Funder
National Health and Medical Research Council
Funding Amount
$408,388.00
Summary
B cells are essential for the protection against infections. This application aims to identify new genes that are crucial for the development or function of B cells and will investigate how mutations in newly discovered genes contribute to defects in the development and function of B cells and the pathogenesis of B cell leukaemia.
Generation Of Protective Immunity Against Severe Influenza Disease In Indigenous Australians
Funder
National Health and Medical Research Council
Funding Amount
$1,630,970.00
Summary
Hospitalisation and death rates from influenza are high in the Indigenous population, especially when a new virus emerges. There is an urgent need for a vaccine that protects against all influenza strains. T cells recognising conserved viral regions elicit such protection. As T cells are restricted by proteins called HLAs, which vary across ethnicities, we will define T cell regions for HLAs prominent in Indigenous Australians and define how to generate protective immunity against influenza.
Protecting Against Malaria Through Liver-resident Memory T Cells
Funder
National Health and Medical Research Council
Funding Amount
$1,196,853.00
Summary
We have shown that formation of liver-resident memory T cells (Trm), a newly discovered type of immune cells, can be induced by an innovative vaccination strategy called prime and trap for highly efficient protection against malaria in mice. Here, we will enhance prime and trap vaccination efficacy by defining the conditions that maximize liver Trm-mediated protection and will characterize simian and human liver Trm cells, paving the way to create the most efficient human malaria vaccine to date
Targeting Caspase 8 In T-Cell Homeostasis And Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,215,780.00
Summary
Chronic infectious diseases such as HIV, hepatitis B and tuberculosis impose a massive global health burden and new treatments are desperately needed. This proposal investigates a new approach to improve immune responses and clear chronic infections. Our multidisciplinary team will define the molecular and cellular biology underlying this approach and translate our findings by re-purposing a drug already approved for other indications in humans.
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.
Modeling Human Actin Related Protein 2/3 Complex Subunit 1B (ARPC1B) Deficiency In Mice
Funder
National Health and Medical Research Council
Funding Amount
$755,005.00
Summary
The actin cytoskeleton forms the structure that not only keeps cells in their normal shape but is also essential for the movement of cells and for interaction between cells. We have recently identified the first patients with an immunodeficiency caused by a defect in a gene called ARPC1B, which plays a crucial role in the regulation of actin. Through the investigation of novel mouse models we will elucidate the pathomechanism underlying the disease of these patients.
Understanding Universal Immunity To Influenza Viruses
Funder
National Health and Medical Research Council
Funding Amount
$687,975.00
Summary
A/Prof Kedzierska’s work combines cutting-edge basic research with unique clinical studies to define how to generate protective immunity against the pandemic and newly emerged influenza viruses. This research will identify key factors that drive the severe and fatal influenza disease in high-risk groups, including the young, elderly, pregnant women and Indigenous Austraians. Findings on the optimal human immunity to influenza viruses will be applicable to other infectious diseases and cancers.