How Does ROCK ‘education’ Of Fibroblasts Drive Neoplastic Progression In The Breast?
Funder
National Health and Medical Research Council
Funding Amount
$636,776.00
Summary
The spread of cancer from one part of the body to another (metastasis) is the main cause of cancer-related death. Metastasis is assisted by the abnormal behaviour of a population of cells called cancer-associated fibroblasts (CAFs). We have identified that activation of an enzyme called ROCK in breast cancers causes an increase in the number of CAFs. We plan to find out how ROCK activation causes this increase in CAFs and find new targets against which breast cancer therapies can be developed.
Molecular Characterisation Of Clathrin-independent Endocytosis In Migrating Cells
Funder
National Health and Medical Research Council
Funding Amount
$870,495.00
Summary
Cell migration is an essential feature of physiological processes involved in embryo development, as well as disease conditions such as cancer metastasis. Cell movement requires extensive changes to the cell surface. We have identified a vital pathway involved in membrane trafficking during cell migration. This proposal aims to identify the cellular components involved in this pathway, screen for new inhibitors, and characterise the role of this pathway in migrating cancer cells.
THE ROLE OF THE TETRASPANINS CD37 AND CD82 IN LEUKOCYTE MIGRATION
Funder
National Health and Medical Research Council
Funding Amount
$370,902.00
Summary
White blood cells must be able to migrate to fight infection. For instance, immune responses are started by the migration of one type of white blood cells to the lymph node. Also, once activated white blood cells migrate out of the circulation to the site of infection where they can kill bacteria and viruses. This grant studies 2 proteins that control white blood cell migration. These proteins may one day be targets for drugs that either promote immunity or reduce inflammation.
Analysis Of Killer T Cell Geometry During An Anti-tumour Response
Funder
National Health and Medical Research Council
Funding Amount
$547,216.00
Summary
Cancer is a major health problem around the world. Currently used treatment options of cancer have the drawback that they also damage healthy tissues. This limits the dosages that can be administered, frequently resulting in treatment failure. Anti-tumour killer T cells are a naturally occurring cell type that can cause tumour regression. In the present proposal, we explore how the efficiency of these cell-types can be further enhanced to induce rejection of progressing tumours.
Dynamics And Mechanisms Of Immune Complex-mediated Skin Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$526,467.00
Summary
Type III hypersensitivity underlies a number of common autoimmune diseases, including rheumatoid arthritis and lupus erythematosus. These diseases are caused by the deposition of immune complexes (IC) and the accumulation of neutrophils within small blood vessels. We will use real time imaging to dissect in space and time the recruitment of neutrophils and IC deposition during type III hypersensitivity reactions in order to better understand the pathogenesis of these conditions.
Functional And Molecular Characterization Of A Novel Regulator Of Angiogenesis
Funder
National Health and Medical Research Council
Funding Amount
$474,907.00
Summary
All cells in the body require blood vessels for the provision of nutrients and waste-removal. A deficiency of vessels prevents proper healing whereas an overabundance is a hallmark of diseases such as cancer and macular degeneration. This research will investigate a novel gene that is essential for new vessel growth. The project aims to understand the mechanism of how this gene functions. Ultimately, the research aims to inform therapeutic development for stimulating or inhibiting vessel growth.
The Role Of Force-sensing Ion Channels In Melanoma Migration
Funder
National Health and Medical Research Council
Funding Amount
$553,848.00
Summary
Metastasis of melanoma cells away from the primary tumour site carries a very poor patient prognosis.This research aims to characterise a novel signalling pathway that can regulate the migration (movement) of melanoma cells. This signalling pathway depends on force-sensing platforms that can rapidly convert physical inputs from the environment into an electrical signal within the cell. We are working to understand how these force-sensors function.
The Mechanism For Combined Immunodeficiency And Autoimmunity Due To STK4-deficiency And Its Broader Application To Human PIDs
Funder
National Health and Medical Research Council
Funding Amount
$648,371.00
Summary
Why do some patients develop autoimmune diseases such as lupus where the immune system makes antibodies that attack its own body? To answer this, we plan to study a disease where a gene responsible for making antibodies is defective. Patients with mutations in the STK4 gene are unable to regulate the selection processes by which only the right cell is chosen to make antibodies. Understanding how STK4 works may help us unlock the mystery of what causes lupus.
Mechanisms Of Immune-evasion By Group A Streptococcus During Skin Infection
Funder
National Health and Medical Research Council
Funding Amount
$602,609.00
Summary
Infections by Group A Streptococcus (GAS), or Streptococcus pyogenes, represent a global health concern. Currently no vaccine exists against GAS thereby mandating a better understanding of the immune response against the bacterium. Using in vivo microscopy, the aim of this proposal is to dissect in real time how neutrophils detect and destroy GAS following skin infection, and how the bacterium manages to circumvent the attack by innate immune cells.
The Role Of The Actomyosin Cytoskeleton In T Cell-mediated Anti-tumour Immunity
Funder
National Health and Medical Research Council
Funding Amount
$616,950.00
Summary
T cells, specialised immune cells, are crucial in the defence against tumours. In order to reach cancerous target cells, T cells must enter tumour tissues from the blood stream and then effectively migrate in the extravascular space. This application aims to uncover the role of the cytoskeleton, a group of molecules driving cell shape change and motility, in the efficient execution of T cell anti-tumour function. These studies will aid the development of improved immunotherapies against cancer.