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.
An Investigation Into The Adaptive Immune Response In Celiac Disease
Funder
National Health and Medical Research Council
Funding Amount
$597,167.00
Summary
Celiac Disease (CD), an autoimmune-like disease that is triggered by the ingestion of dietary wheat gluten, or related proteins from rye and barely, affects ~1% of the population, causing tissue damage in the small intestine. The only available treatment is strict adherence to a lifelong gluten free diet. Our project aims to understand, at the molecular level, how components of the immune system and gluten interact to trigger the immune response that leads to CD symptoms.
Defining The Molecular And Functional Features Of Protective HIV-specific T Cells
Funder
National Health and Medical Research Council
Funding Amount
$591,966.00
Summary
Human immunodeficiency virus (HIV) directly attacks our immune system, impairing our natural defense against infection and disease. HIV has claimed over 39 million lives worldwide since its discovery, and no vaccine is currently available. Despite this, there are some individuals with a particular genetic advantage able to control HIV infection who never get sick. Understanding how these individuals control HIV so efficiently may lead to novel treatments or potential vaccines against HIV.
Exploring the immunomodulatory potential of Natural Killer T cells. Natural Killer T cells (NKT cells) are an innate-like population of T cells that recognise a range of lipid based antigens when bound to the antigen-presenting molecule, CD1d. Once activated, NKT cells rapidly secrete a variety of cytokines. This project, in partnership with Vaxine Pty Ltd, aims to gain a basic understanding of NKT recognition of lipids and NKT cell activation by lipids. The project aims to use a combination of ....Exploring the immunomodulatory potential of Natural Killer T cells. Natural Killer T cells (NKT cells) are an innate-like population of T cells that recognise a range of lipid based antigens when bound to the antigen-presenting molecule, CD1d. Once activated, NKT cells rapidly secrete a variety of cytokines. This project, in partnership with Vaxine Pty Ltd, aims to gain a basic understanding of NKT recognition of lipids and NKT cell activation by lipids. The project aims to use a combination of cellular immunology and structural biology to gain insight into NKT cell agonism.Read moreRead less
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.
Structural Investigations Of The Bcl-2 Family Cell Death Apparatus
Funder
National Health and Medical Research Council
Funding Amount
$612,652.00
Summary
Programmed Cell Death is a process by which dangerous cells are removed from the body. Sometimes it goes wrong and causes disease, e.g. cancer cells stay alive when they should die. This project will study a group of proteins that regulate cell death, the Bcl-2 family of proteins, in order to understand the mechanism by which they control the balance of cell life and death. The findings will inform the development of new drugs aimed at regulating cell death in a variety of disease states.
Metabolite regulation of mitochondrial fission. This project aims to understand how the function and health of mitochondria – the energy producing structures in cells - are controlled by fat molecules. The project expects to integrate cutting edge techniques and instrumentation to generate new knowledge of how fat molecules interact with, and influence, enzymes that control how cells maintain their mitochondria in response to nutrient state. An anticipated goal is to define a fingerprint for enz ....Metabolite regulation of mitochondrial fission. This project aims to understand how the function and health of mitochondria – the energy producing structures in cells - are controlled by fat molecules. The project expects to integrate cutting edge techniques and instrumentation to generate new knowledge of how fat molecules interact with, and influence, enzymes that control how cells maintain their mitochondria in response to nutrient state. An anticipated goal is to define a fingerprint for enzymes regulated by fat molecules that will be of great interest to researchers across many branches of life sciences. Expected outcomes and benefits will be deeper understanding of fat molecules as nutrient signalling metabolites, and how they influence cell metabolism, growth and development.Read moreRead less
The structure of heteromeric amyloid fibrils with signaling activity. This project aims to determine the composition, structure and properties of important protein complexes involved in a newly identified cell death pathway known as necroptosis. This cell death pathway removes unwanted or damaged cells during development or infection. These necroptosis protein complexes are unusual because they have a fibrillar amyloid structure, contain more than one protein type in the fibrils and have a funct ....The structure of heteromeric amyloid fibrils with signaling activity. This project aims to determine the composition, structure and properties of important protein complexes involved in a newly identified cell death pathway known as necroptosis. This cell death pathway removes unwanted or damaged cells during development or infection. These necroptosis protein complexes are unusual because they have a fibrillar amyloid structure, contain more than one protein type in the fibrils and have a functional, signalling role. The research will determine how these fibrils form and how the structures confers biological function. It could identify features in these fibrils that can be targeted as a means of ultimately preventing tissue damage after heart attack and stroke.Read moreRead less
Inhibiting protein-protein interactions involved in neural development and disease. This project will determine the molecular mechanisms by which the protein LMO4 (a regulator of brain development) binds to DEAF1 (which also regulates neural development) and CtIP (which protects against tumour formation). This will allow a set of reagents to be developed to help determine the functions of LMO4, and may ultimately be used to treat disease.
Crosstalk between cell survival and cell death pathways. This project aims to determine the precise molecular mechanisms underlying cell fate decisions. The dynamics between cell survival (autophagy) and cell death (apoptosis) are complex, involving significant crosstalk between these pathways. This is fundamentally important to cellular processes. Aberrant control of autophagy and apoptosis affects the function of all organisms as well as the development and treatment of diseases ranging from c ....Crosstalk between cell survival and cell death pathways. This project aims to determine the precise molecular mechanisms underlying cell fate decisions. The dynamics between cell survival (autophagy) and cell death (apoptosis) are complex, involving significant crosstalk between these pathways. This is fundamentally important to cellular processes. Aberrant control of autophagy and apoptosis affects the function of all organisms as well as the development and treatment of diseases ranging from cancer to heart disease. This project endeavours to advance our understanding of the proteins that interconnect autophagy and apoptosis. The results are expected to explain how cells determine their fate and inform future development of strategies to treat disease.Read moreRead less