Plasmin is a complex enzyme that performs major roles in removal of blood clots, wound healing and in tumor metastasis. Here we will understand how plasmin function is regulated at the molecular level. These key insights will be of future use in the development of therapeutics targeting the plasmin system in cancer and clotting diseases.
Structural Studies On The Immune Effector Perforin: Developing Mechanism-based Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$1,116,594.00
Summary
Perforin is an essential weapon deployed by the human immune cells in order to destroy virally infected or cancerous cells. Despite this key role, unwanted or excessive perforin function can result in disease and can severely impact on successful treatment of leukaemia through bone marrow transplantation. This application aims to understand the molecular details of perforin function, and to apply this knowledge to develop perforin inhibitors.
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.
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.
Molecular And Structural Basis Of Signalling By TIR Domain-containing Adaptors In TLR Pathways
Funder
National Health and Medical Research Council
Funding Amount
$666,417.00
Summary
Humans first detect the presence of pathogens and respond to them through specific pathways termed innate immune pathways. The proposed research will study proteins that participate in these pathways, in particular their three-dimensional structures and how they interact with each other, to understand how they work together to mount an immune response, and to find ways to modulate this response in infectious diseases as well as chronic inflammatory diseases.
Structural Investigations Of The Bax And Bak Cell Death Apparatus
Funder
National Health and Medical Research Council
Funding Amount
$275,509.00
Summary
Programmed cell death is a process by which the body keeps rogue cells in check. Cancer cells adapt to avoid this process and thus evade this important defence mechanism. This project seeks to understand the machinery that controls programmed cell death at the molecular level. It will provide the atomic details of how this machinery is regulated and how it functions to induce cell death. These insights will provide new avenues for targeting this machinery for a new generation of cancer therapeut ....Programmed cell death is a process by which the body keeps rogue cells in check. Cancer cells adapt to avoid this process and thus evade this important defence mechanism. This project seeks to understand the machinery that controls programmed cell death at the molecular level. It will provide the atomic details of how this machinery is regulated and how it functions to induce cell death. These insights will provide new avenues for targeting this machinery for a new generation of cancer therapeutics.Read moreRead less
Dissecting The Molecular Basis Of Actin Filament Disassembly In The Malaria Parasite
Funder
National Health and Medical Research Council
Funding Amount
$576,716.00
Summary
Cell movement by the malaria parasites is fundamental to parasite infection and disease. However, whilst core components of the parasite motor driving movement are known, little is understood about their regulation, in particular actin – the dynamic force behind all parasite motility. Here by dissecting the role of actin-depolymerizing-factor-1, an essential parasite actin regulator, we hope to reveal one of the central processes that underlies motility and develop it into a potential drug targe ....Cell movement by the malaria parasites is fundamental to parasite infection and disease. However, whilst core components of the parasite motor driving movement are known, little is understood about their regulation, in particular actin – the dynamic force behind all parasite motility. Here by dissecting the role of actin-depolymerizing-factor-1, an essential parasite actin regulator, we hope to reveal one of the central processes that underlies motility and develop it into a potential drug target.Read moreRead less
Understanding The Structure And Function Of The Chromosome Condensin Complex
Funder
National Health and Medical Research Council
Funding Amount
$620,731.00
Summary
In order to survive cells need to divide their genetic material (DNA) equally between two daughter cells. For correct cell division to occur DNA has to be correctly packaged into condensed and organised chromosomes. Improper packaging of genetic material can result in unregulated cells that may become cancerous or lead to other genetic diseases such as Down's Syndrome. Understanding the key players regulating this process is vital to allowing researchers to further work in these areas.
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.