Artificial Synthesis Of The Type III Secretion System Translocon. A New Approach To Vaccine Design
Funder
National Health and Medical Research Council
Funding Amount
$668,742.00
Summary
Today hospitals are plagued with bacterial infections that do not respond to antibiotics. The problem exists because although antibiotics are effective at killing bacteria, this paradoxically also helps the drug-resistant bacteria thrive. We will pioneer a completely new approach to vaccine design that allows us to construct a vaccine that protects us from bacterial infection without killing the bacteria. The vaccine should therefore be far less susceptible to drug resistance.
Structural And Functional Investigation Of Killer-Cell Immunoglobulin-like Receptors
Funder
National Health and Medical Research Council
Funding Amount
$546,966.00
Summary
Natural Killer (NK) cells are an important component of the immune response to cancer and infection. This project will define the molecular targets that are recognised by NK cells. This knowledge can then be used as a guide in the selection of bone marrow donors in the treatment of leukaemias as well as understanding how we fight infections.
Characterization And Inhibition Of Higher-order Assembly Signalling In Toll-like Receptor Pathways
Funder
National Health and Medical Research Council
Funding Amount
$711,995.00
Summary
The innate immune system is the first line of defence against pathogens. Inhibitors of innate immune pathways can be developed into therapeutic agents against a number of disorders including chronic inflammatory diseases, such as rheumatoid arthritis. We have discovered a new mechanisms of signaling by a set of key molecules in these pathways, through formation of large assemblies. We will characterize these assemblies and uncover ways to inhibit their formation.
A Structural, Chemical And Functional Investigation Into MAIT Cell Receptor Recognition
Funder
National Health and Medical Research Council
Funding Amount
$1,196,304.00
Summary
This project is focused on a type of T-cell, termed a MAIT cell, which is found abundantly in the lining of the gut. We are investigating how this MAIT cell is activated by riboflavin and folic acid metabolites. We are also examining how commonly prescribed drugs impact MAIT cells and how such activation may be linked to diseases, including inflammatory bowel disease.
Cytokine Structure And Mechanisms Of A Superagonist Antibody
Funder
National Health and Medical Research Council
Funding Amount
$349,590.00
Summary
Monoclonal antibodies are widely used in diagnosis and therapy due to their outstanding specificity and safety. The monoclonal antibodies recognizing cytokines with enhancing functions are an emerging class of novel reagents in immunotherapy. This project is to investigate how a newly indentified monoclonal antibody enhances the activity of a cytokine and use this immunostimulatory function to design new strategies for better vaccination and treatment for cancer and infection.
An Investigation Into The Molecular Basis Of MAIT Cell Recognition Of Vitamin B Based Metabolites
Funder
National Health and Medical Research Council
Funding Amount
$883,762.00
Summary
Mucosal associated invariant T cells (MAIT cells) are an abundant T-cell population in humans, that is found mostly in the gastrointestinal mucosa. We have recently shown that MAIT cells can be activated by metabolites of vitamin B. This proposal will investigate how the MAIT cells "see" vitamin B metabolites. This research will pave the way for novel therapeutics that can modulate MAIT cell activity.
A Molecular Investigation Into Lipid-reactive Immunity To Combat Mycobacterium Tuberculosis Infection
Funder
National Health and Medical Research Council
Funding Amount
$628,152.00
Summary
Tuberculosis (TB) infection currently causes ~1.5 million deaths annually. Due to new survival features acquired by the causative agent (Mycobacterium tuberculosis), traditional TB drugs and vaccines are becoming inefficient. Mycobacterium tuberculosis has a protective lipid-dense cell wall that is targeted by our immune system. We aim to understand the mechanisms of the lipid-mediated immune response to TB in order to develop more effective strategies to combat this disease.
Understanding The Development Of Autoimmunity In Response To Citrullinated Peptide Antigen Presentation To T Cells In Rheumatoid Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$1,181,793.00
Summary
Rheumatoid arthritis (RA) is a systemic autoimmune disease predominantly affecting synovial joints, in 1% of adults worldwide. HLA-class II genes underlie the major genetic susceptibility to RA. The programme of work brings together 7 investigators from 3 countries to determine how autoimmunity develops to self antigens in individuals at genetic risk of RA and why resistance alleles are protective against RA, in Caucasian, Asian and North American Native populations. We will provide a molecular
Investigating CRAC Channel Assembly And Interactions Important In Immunity
Funder
National Health and Medical Research Council
Funding Amount
$398,247.00
Summary
#ERROR: -Transmission and amplification of signals between subcellular compartments underpins cell function. Calcium ions are cellular messengers that can cross Membranes using specialised pores. CRAC Calcium channels in particular are critical for immune system function,and partner Proteins switch them on and off in a feedback response to compartmental Calcium levels. the objective of my research is to investigate how opening and closing of the CRAC pore is triggered at a molecular level.
Recognition Of Lipid Antigens By CD1d-restricted Type-2 NKT Cells
Funder
National Health and Medical Research Council
Funding Amount
$417,684.00
Summary
Protection against infection depends on T cells, which recognise and target foreign molecules called antigens via a specialized antigen receptor known as a T cell receptor (TCR). This project focuses on a specialised population of T cells called Natural Killer T (NKT) cells that recognise lipid antigens. The work outlined in this grant will increase our understanding of how different TCRs can recognise diverse lipid antigens thus providing insight into the role of NKT cells in the immune system.