Flaviviruses Must Come Of Age: Design Of Stable, Mature Particles By Structural Vaccinology
Funder
National Health and Medical Research Council
Funding Amount
$1,149,487.00
Summary
We have established a powerful toolset combining advanced structural biology and rapid virus engineering that allows us investigate the assembly of flaviviruses in novel ways. This project will integrate these approaches to investigate the role of new ligands that we have identified in the structure of medically-relevant flaviviruses including dengue virus and delineate a novel maturation path for flaviviruses, which will be used to design safer and more effective flavivirus vaccines.
Structure And Mechanism Of Activation Of The Mechanosensitive Ion Channel TACAN
Funder
National Health and Medical Research Council
Funding Amount
$997,537.00
Summary
We propose to determine the structure and mechanism of activation of TACAN, a recently identified ion channel that defines a novel and uncharacterised class of channels. TACAN is specifically involved in sensing mechanical pain and contributes to mechanosensitive currents in the pain-receptor type of neurons. Our studies will increase knowledge of this novel class of proteins that will allow for the future development of treatments for several chronic pain conditions including arthritis.
The Ins And Outs Of Endocytosis Inhibition: Providing Diverse Opportunities For Treatment Of Incurable Cancers
Funder
National Health and Medical Research Council
Funding Amount
$912,353.00
Summary
The best new immune system anti-cancer drugs only work in ~30% of patients. We found a way to move the drug targets around in people's tumours temporarily to reverse resistance and have tested this in clinical trials. Here we propose to use immunology and the world's frontier electron microscope techniques to work out exactly what is happens to the tumours, immune cells and anti-cancer drugs when they interact in real clinical situations. The aim is to reach at least 60% patient response rate.
Shedding Light Onto The Structural Secrets Inside Pluripotent Stem Cells In Real-time
Funder
National Health and Medical Research Council
Funding Amount
$555,890.00
Summary
To meet the challenges of life, a human being requires 30 trillion cells, a blue whale a staggering 100 quadrillion. This vast diversity of cells derives from very few unspecialised cells that can become any cell type of the adult body - the pluripotent stem cells. We will use innovative imaging techniques to uncover the cellular architecture of pluripotency to provide critical insights into how the various parts of a versatile cell, its cytoskeleton and organelles, are assembled in real-time.
The rapid interactions of circulating human blood platelets is critical to prevent bleeding, but can cause thrombotic diseases (heart attack, stroke). These highly regulated interactions involve specific adhesive proteins. Our studies will define factors regulating platelet interactions. Imaging the thrombotic process will quantify platelet function at an unprecedented resolution and we have a panel of new candidate reagents that will be assessed for antithrombotic potential.
Unraveling the variability in the protein expression in tissues or cell populations is critical to understand how cells respond to their environment. For example, this can provide details about the cellular response to an infection or to a chemoterapic. As of today, single cell protein analyses has become at reach, but its application is still cumbersome and its throughput is low. This proposal aims to develop and deploy a simple and robust method to analyse the protein content in single cells.