Integrating Immunity And Genetics In Follicular Lymphoma To Establish A Prognostic Score Fit For The Modern Era
Funder
National Health and Medical Research Council
Funding Amount
$1,377,174.00
Summary
Follicular lymphoma (FL) is divided into early and advanced stages. Early stage FL is frequently cured, but there is no way to identify who will be cured and who won't. By contrast advanced stage FL is incurable. Our unique access to well-annotated clinical trial and population based cohorts allows us to perform a detailed biological comparison of early and advanced FL, to gain a deeper understanding of the impediments to eradicating the disease, and to predict outcome to conventional therapy.
Attenuating Severe Infections In Chronic Inflammatory Diseases Through Modulation Of Transforming Growth Factor-β Activity
Funder
National Health and Medical Research Council
Funding Amount
$611,793.00
Summary
Asthma and chronic obstructive pulmonary disease (COPD) are characterised by enhanced TGF? expression, which is accompanied by susceptibility to recurrent viral and bacterial infections. Such infections exacerbate lung inflammation in these patients, generally requiring emergency department treatment. This project proposes to clarify the therapeutic potential of TGF? inhibitors to reduce the impact of viral infections in patients with COPD and asthma.
Characterization Of Novel, Colitis Associated Pathobionts To Identify Therapeutic Targets In The Host Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$684,609.00
Summary
Applying cutting edge methods to grow bacteria from the human gut, we have identified three species, two previously unknown, that are found in many inflammatory diseases including Inflammatory bowel disease, colorectal cancer and in cancer immunotherapy patients who experience colitis. By characterizing these bacteria and the immune response in human cells we are seeking to discover novel targetted methods to prevent colitis and gastrointestinal inflammation.
Targeting Caspase 8 In T-Cell Homeostasis And Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,215,780.00
Summary
Chronic infectious diseases such as HIV, hepatitis B and tuberculosis impose a massive global health burden and new treatments are desperately needed. This proposal investigates a new approach to improve immune responses and clear chronic infections. Our multidisciplinary team will define the molecular and cellular biology underlying this approach and translate our findings by re-purposing a drug already approved for other indications in humans.
ROLE OF RIP KINASES & IAPs IN MUCOSAL IMMUNE DEFENCE
Funder
National Health and Medical Research Council
Funding Amount
$631,168.00
Summary
Pathogenic bacteria are master manipulators of the inflammatory signalling pathways designed to thwart them. Understanding how they do this will allow us to develop drugs that limit their ability to infect. We have shown that pathogenic bacteria inject a protein called EspL into human cells to promote the destruction of a family of human proteins, called RIP Kinases (RIPK), that co-ordinate the inflammatory response and aim now to discover how EspL causes RIPK degradation and thereby promotes in ....Pathogenic bacteria are master manipulators of the inflammatory signalling pathways designed to thwart them. Understanding how they do this will allow us to develop drugs that limit their ability to infect. We have shown that pathogenic bacteria inject a protein called EspL into human cells to promote the destruction of a family of human proteins, called RIP Kinases (RIPK), that co-ordinate the inflammatory response and aim now to discover how EspL causes RIPK degradation and thereby promotes infection.Read moreRead less
Norovirus Infection At The Stress Granule-PKR-p-elF2α Axis
Funder
National Health and Medical Research Council
Funding Amount
$505,967.00
Summary
This project application will aim to investigate and understand how viruses that cause vomiting and diarrhoea are able to infect, proliferate and spread within the human body. It aims to address how viruses are able to avoid and replicate in the presence of an effective immune response. We have evidence showing that Noroviruses are able to exploit certain antiviral proteins to paradoxically aid in virus replication and survival.
A specialised set of T lymphocytes called Mucosal Associated Invariant T (MAIT) cells react against bacteria and yeast, and reside at mucosal sites where the body's immune defences are most easily breached, e.g. respiratory tract and intestinal mucosa. This study investigates the role of MAIT cells in both protection and pathology in bacterial infections. Controlling MAIT cells could help in treating these conditions.
Regulation Of NOD Signalling By IAPs And RIP Kinases
Funder
National Health and Medical Research Council
Funding Amount
$643,172.00
Summary
Alterations in NOD signalling have been implicated in various human inflammatory diseases, particularly in Crohn’s disease and asthma. In this project we will identify new molecules that regulate NOD signalling and test the effect of drugs that inhibit known components of these pathways to determine their utility in treating inflammatory diseases.
Host Cell Death Signaling And Susceptibility To Bacterial Gut Infection
Funder
National Health and Medical Research Council
Funding Amount
$682,321.00
Summary
Bacterial infections are a major cause of infectious disease worldwide. Here we aim to characterise immune responses that help fight infection by E. coli and Salmonella. These bacteria have evolved ways to shut down many of our immune responses during infection, allowing them to survive and cause disease. This work will help understand the complex relationship between gut bacteria and our immune system and provide solutions for controlling infection and treating immune disorders of the gut.
The Role Of Co-signalling Receptors In Cytotoxic Lymphocyte Activity During Infection And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$739,657.00
Summary
Cytotoxic lymphocytes (CLs) are immune cells that detect and kill cancer cells. CLs recognise ‘stress’ proteins on cancer cells through specialised receptors, and this provides the signal for them to kill. However, some cancer cells, such as leukemic cells, can interfere with this recognition to avoid killing by immune cells. This project will investigate the mechanism of recognition and killing of cancer cells by CLs, using both mouse models and cells from patients with acute myeloid leukemia.