The Molecular Basis By Which The Interleukin-6 Cytokine Promotes Emphysema
Funder
National Health and Medical Research Council
Funding Amount
$659,457.00
Summary
Interleukin 6 (IL-6) is a potent immuno-modulatory cytokine that is commonly elevated in emphysema, the 5th leading cause of death in Australia. To understand the role of IL-6 in emphysema, we aim to demonstrate here by using a unique mouse model for IL-6-driven emphysema and clinical biopsies from emphysema patients, that IL-6 uses an alternative signalling mechanism in emphysema termed trans-signalling. Therefore this project could provide novel therapeutic targets for emphysema.
A Novel Class Of Negative Regulators Of Interleukin-6 Signalling
Funder
National Health and Medical Research Council
Funding Amount
$626,950.00
Summary
Cytokines are protein messengers that activate the immune system to fight infections. When they are too active they cause inflammation and autoimmune diseases so their activity needs to be tightly controlled. We have discovered a new family of regulators (the MARCH proteins) that inhibit cytokine activity by routing cytokine receptors for destruction. We aim to understand how this process works in detail and the role of MARCH proteins in vivo in ameliorating autoimmune diseases.
Treating and preventing painful fractures could be improved by strengthening cortical bone – the hard outer shell of all bones in the skeleton. We don’t know how cortical bone forms, but if we did, we could improve its strength. We have found that a brain-like network of cells inside the skeleton, called osteocytes, use a specific signal, called SOCS3, to make strong cortical bone. This study will find out how SOCS3 works and find new ways to make cortical bone strong and healthy.
Interleukin-1β Biology: Mechanisms Of Regulation, Activation And Secretion
Funder
National Health and Medical Research Council
Funding Amount
$641,979.00
Summary
The protein called intelreukin-1 (IL-1) is required to fight off invading pathogens but more recently has been implicated as contributing to diverse diseases characterised by excessive inflammation, such as arthritis, gout, atherosclerosis and even cancer. This project aims to understand how IL-1 is made within cells and then activated to cause inflammation, which will enable these processes to be therapeutically targeted.
Overcoming Therapeutic Resistance In Pancreatic Cancer
Funder
National Health and Medical Research Council
Funding Amount
$924,901.00
Summary
Pancreatic cancers arise when abnormal cells grow out from otherwise normal tissue. The resulting tumours contain a number of different types of cells, some of which help the tumour to grow, and some of which fight the tumour. We are interested in understanding how soluble molecules called cytokines influence the cells that promote tumour growth and metastasis. In particular, we will test whether cytokine inhibitors can overcome tumour resistance to chemotherapy.
The Role Of Cell Death Pathways In Inflammation And Pathogen Infection
Funder
National Health and Medical Research Council
Funding Amount
$415,218.00
Summary
Cell death and inflammation are essential for protection against pathogen infection but can also cause human diseases. Inflammation caused by the IL-1? protein has been implicated in diseases such as type II diabetes, arthritis and cancer. This project aims to elucidate how IL-1? protein activity is regulated at the molecular level. It also seeks to understand how the pathogen responsible for Legionnaires’ disease manipulates cell death to allow for successful invasion of the human host.
Mechanisms Of Cytokine Independence During The Development Of Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$598,163.00
Summary
Signals from growth factors such as cytokines and hormones are required for cell survival. In their absence cells activate an in-built self-destruct process. Determining how cytokines regulate cell death will provide novel targets so that unwanted cells (like cancer cells) can be triggered to die and needed cells (such as brain cells) can survive.
Regulation Of Interleukin-1? Activation In Inflammatory Diseases
Funder
National Health and Medical Research Council
Funding Amount
$624,429.00
Summary
IL-1? protein is required to combat infection but also contributes to inflammatory diseases, such as Rheumatoid arthritis and diabetes. Understanding how IL-1? is produced is therefore critical to the development of better therapeutics for these conditions. We have identified a new pathway involving the protein RIP3 that can cause IL-1? activation. This project will examine how this pathway is molecularly regulated and determine its importance in inflammatory disease models.