I am a biochemist focussed on understanding how the structures of proteins determine their functions. I intend to apply this understanding to medically relevant questions by working collaboratively and using a range of complementary structural, computational and cell biology techniques. In particular, I will focus on proteins involved in infection and immunity, to understand how they work, and contribute to the development of drugs and vaccines.
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.
Under this fellowship the applicant will study a n important group of enzymes and molecular delivery machines involved in clotting disease, immune dysfunction and cancer.
Host-virus Protein Complexes In The Immune System Response To Influenza
Funder
National Health and Medical Research Council
Funding Amount
$316,449.00
Summary
This proposal will investigate the inhibition of the human immune response by viruses. Specifically, an enzyme, TRIM25, which ubiquitinates proteins important for signalling the viral immune response has recently been shown to be inhibited by the non-structural influenza protein NS1. The mechanism of this inhibition is unknown and is thus the subject of this project.
How Do TRIM21 And TRIM5α Execute Dual Antiviral Effector And Signalling Functions?
Funder
National Health and Medical Research Council
Funding Amount
$344,724.00
Summary
We encounter millions of potential pathogens each day that must be detected and disarmed by the immune system. Recently, two antiviral proteins, present inside cells, were shown to both detect viruses, alerting neighbouring cells to the infection, and target the viruses for destruction. These two functions provide important protection against viral infection and this research aims to understand at a molecular level, how these dual antiviral functions are coordinated.
Structural Biology And Therapeutic Targeting Of Proteins Involved In Infection And Immunity
Funder
National Health and Medical Research Council
Funding Amount
$753,300.00
Summary
Structural biology plays an essential role in uncovering how proteins function at the molecular level, and further facilitates strategies to develop therapeutics targeting the diseases these proteins are involved in. In the proposed work, I will focus on bacterial virulence factors, to develop new antibiotics and vaccination strategies, and proteins involved in innate immunity pathways, to develop therapeutics against a number of associated disorders including chronic inflammatory diseases.
Protein-RNA Interactions In Antiviral Cellular Defence And Gene Regulation
Funder
National Health and Medical Research Council
Funding Amount
$705,501.00
Summary
Protein-RNA interactions play key roles in antiviral cellular defence and inflammation. Investigation of these molecular interactions will lead to new therapeutic targets and means of combating virus-related disease and inflammatory disorders.
Molecular Basis For RIG-I Like Receptor Activation Of The Innate Immune Pathway.
Funder
National Health and Medical Research Council
Funding Amount
$564,770.00
Summary
This project is to understand how proteins in the cell detect the presence of invading viruses, and pass on the message for the cell to produce defence molecules. The overproduction of these defence molecules can lead to inflammatory diseases. This research will help us to understand the process of the innate immune response in cells and how we might control it in disease states.
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.
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.