The regulation to early T cell signalling is a critical step in immune responses. Superimposed onto the biochemical pathways is a spatial organization that defines the immunological synapse. My research aims to map the principles of the spatial organization on the molecular scale to identify how lipids could unbalance the dynamic signalling equilibrium, for example in obese patients. To achieve this goal, my research group has developed single molecule microscopy approaches.
Understanding The Role Of The Putative Phospholipid Translocase ATP11c In B Cell Development
Funder
National Health and Medical Research Council
Funding Amount
$455,153.00
Summary
The immune system protects humans against recurrent infections with a wide range of pathogens. Formation of antibodies is a crucial element of the immune response. Defects in the production of antibodies can lead to recurrent and often life-threatening infections. This project seeks to understand a genetic defect in mice resulting in an almost complete absence of antibody producing cells, thereby causing a disease that is similar to some forms of human immunodeficiency.
Deciphering Signalling Pathways Regulating Iron Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$407,402.00
Summary
Iron overload and anaemia are two of the most significant health problems affecting humans. Understanding how the body regulates iron levels is key to our understanding of these disorders and to the future development of new therapies. This research is aimed at understanding how a hormone produced in the liver called hepcidin that maintains iron balance is regulated. This research may lead to novel therapies aimed at correcting the iron balance in conditions of iron overload or anaemia.
Understanding The Molecular Basis Of Epididymal Maturation: How Does The Epididymis Modify Spermatozoa, Allowing Them To Recognise The Egg ?
Funder
National Health and Medical Research Council
Funding Amount
$585,898.00
Summary
Male infertility is a significant clinical problem affecting one in twenty Australian men. A common feature of this condition is the sperm’s inability to recognize the egg. Sperm gain this property as they transit an organ known as the epididymis. We have produced genetically modified mice with a specific epididymal defect that prevents sperm-egg recognition. This study will examine the structure of these defective sperm to generate new insights into the molecular basis of sperm-egg interaction.
The Implications Of Focal Adhesion Organization On Signal Transduction
Funder
National Health and Medical Research Council
Funding Amount
$565,614.00
Summary
The areas of a cell's attachment to their surroundings are known as focal adhesion. Apart from linking the inside and outside of a cell, focal adhesions act as a communication centre transmitting incoming and outgoing signals. How focal adhesions themselves are organized is currently not known. We propose to adhere cells to model surfaces to control the protein and membrane structure of focal adhesions and measure how focal adhesion structure affects cell communication.
Multiscale Analysis Of Plasma Membrane Microdomains In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$863,413.00
Summary
The cell surface encloses the cell in a protective barrier but it must also respond to signals coming from outside the cell. To accomplish this, the cell surface is made up of numerous regions each with a specialised role. This proposal aims to examine how lipids and proteins work together to make these specialised regions and aims to understand what goes wrong in diseases such as muscular dystrophy.
Macrophage Polarisation And Control Of Pulmonary Inflammation.
Funder
National Health and Medical Research Council
Funding Amount
$895,494.00
Summary
As key immune cells, macrophages are polarised to phenotypes that turn inflammation on or off. In cystic fibrosis, defective macrophage polarisation enhances inflammation and prevents lung repair. We are defining the molecules and cellular pathways that control this process and identifying targets for existing drugs that can be used to reprogram macrophages and restore lung repair to improve patient outcomes.
Novel Approaches To Control Mast Cell Function In Allergic Inflammation.
Funder
National Health and Medical Research Council
Funding Amount
$723,447.00
Summary
Allergic disorders are a major health problem. Driven by mast cells, the underlying inflammation is exacerbated by the ‘?c family’ of cytokines acting on the surface of these cells. We aim to characterise the ‘mast cell-?c axis’ with the view to developing new therapies based on our ?c receptors blocking antibodies. This path of discovery-mechanism-translation seeks to recapitulate our previous success of taking a related antibody to Phase II clinical trials to treat patients with leukaemia.
Mechanisms Of Ligand-Selective Signalling By Chemokine Receptors
Funder
National Health and Medical Research Council
Funding Amount
$749,428.00
Summary
Receptors are molecules located on the surfaces of cells. They control the response of one cell to chemical signals emitted by different cells. In this project we aim to characterise and understand the molecular details of how a receptor can respond differently to distinct chemical signals. The results of this study will help to guide future development of medicines to control white blood cell migration into tissues during inflammatory diseases such as heart disease, diabetes and arthritis.