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.
Structural Basis Of The Transcription Of Housekeeping Genes
Funder
National Health and Medical Research Council
Funding Amount
$314,644.00
Summary
TFIID, which is a regulator of cell growth and proliferation, has been identified as a new cancer drug target. However, more information on TFIID's mechanisms of regulation is required before such drugs can be designed. This project will fill this gap in understanding and enable the development of new cancer therapies.
Acetohydroxyacid Synthase: A New Drug Target For Human Fungal Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$536,914.00
Summary
The aim is to discover new compounds that have the ability to reduce the growth of invasive human fungal pathogens including Candida albicans, Cryptococcus neoformans and Aspergillus nidulans. These infectious agents are highly prevalent in hospital patients that are immuno-compromised. The compounds have a common feature in that they prevent the synthesis of valine, leucine and isoleucine which are key metabolites required for the survival of these fungi in the human host.
Determining Fundamental Mechanisms Compromised In Kir-linked Disease States
Funder
National Health and Medical Research Council
Funding Amount
$600,040.00
Summary
The human nervous system and organs are reliant on precisely controlled transmission of electrical currents through sodium and potassium channels. Their core functions are compromised when currents fail to switch on and off normally. Faulty potassium channels are implicated in diabetes, epilepsy and heart failure. This project re-examines the mechanisms controlling potassium channels, with a view to scientific and therapeutic discrimination between the different classes present in human cells.
Understanding The Role Of The Scaffolding Protein D13 In Poxvirus Assembly And Its Inhibition By Rifampicin
Funder
National Health and Medical Research Council
Funding Amount
$371,275.00
Summary
Smallpox is one the most notorious diseases in human history. Despite its eradication in the 1970s, human cases of animal poxviruses such as monkeypox virus and the potential use of smallpox as a bioterrorism weapon have called for an improved preparedness of Australia against (re)-emerging poxviruses. This project combines structural biology approaches to understand the complex assembly of poxviruses and provide the basis for the development of broad-spectrum antiviral drugs.
Coupling The Cell Cortex To Membranes: Structural Basis For The Activation And Control Of Ezrin
Funder
National Health and Medical Research Council
Funding Amount
$587,548.00
Summary
Cells are dynamic: they change shape, communicate with each other and import/export signalling molecules. These dynamic processes are controlled via the interaction of the cell membrane with the underlying actin cytoskeleton and they are important for health, for example, they are critical for proper immune cell function. The goal of this project in to unravel the control of membrane dynamics by defining the interactions between the cell membrane and the proteins: ezrin and RhoA.
Novel Insights Into The Molecular Mechanisms Of Manganese Recognition And Acquisition By Pathogenic Bacteria.
Funder
National Health and Medical Research Council
Funding Amount
$843,035.00
Summary
Streptococcus pneumoniae is the world’s foremost bacterial pathogen. In Australia, bacterial infections are responsible for more than 9000 deaths every year, and the economic burden associated with treating diseases arising from pneumococcal infections is more than $4 billion annually. This proposal aims to define the molecular basis of how bacteria scavenge manganese from the host environment. This knowledge will provide the foundation for next generation antimicrobial therapeutics.
Mechanism Of Anoxic Iron Acquisition In Pathogenic Bacteria
Funder
National Health and Medical Research Council
Funding Amount
$536,280.00
Summary
All organisms require iron for their survival, including all bacterial species. Bacterial pathogens growing in anaerobic environments, such as in our gut, gum, or tissue, sequester iron through the divalent iron transporter FeoB. We aim to divulge the mechanism of iron transport through FeoB by structural and functional studies, and thus provide a scaffold for a non-conventional antimicrobial target.