Type I Interferon Signalling In Bacterial Infection
Funder
National Health and Medical Research Council
Funding Amount
$738,274.00
Summary
Infectious diseases are a leading cause of death in Australia. Activation of disease-fighting inflammasomes sets in motion rapid immune defenses against pathogens. In this project, we explore how cell-cell communication molecules known as type I interferons communicate with inflammasomes to achieve the best outcome in the body in response to deadly bacterial infection. Understanding how these signals communicate with one another could reveal new ways to fight infectious diseases.
Understanding Neuroinflammation In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,043,216.00
Summary
This project opens a new line of enquiry into the cellular signalling mechanisms involved in the progression of AD and establishes whether targeting the involvement of type-1 IFN signalling influences the evolution of AD. New and novel approaches are clearly required to treat AD. Importantly, we believe that neuroinflammation is common to all causes of dementia and targeting the neuroinflammatory pathways has much wider implications than targeting the primary causative pathway.
Role Of Obesity In Impaired Treatment Response In Chronic Hepatitis C: Mechanisms And Therapeutic Strategies
Funder
National Health and Medical Research Council
Funding Amount
$540,075.00
Summary
The overall objective of this Research Project is to examine the mechanisms by which obesity and fatty liver impair the response to antiviral treatment in patients with chronic hepatitis C and to develop specific strategies to monitor and improve the outcome of treatment. In addition, the development of non-invasive strategies and surrogate cell culture systems for the assessment and serial monitoring of the antiviral response will be of substantial benefit.
Functional Pharmacogenetics: Analysis Of The Functional Effect Of The IL28B Genotype On Hepatitis C Virus Infection And Treatment Response.
Funder
National Health and Medical Research Council
Funding Amount
$93,843.00
Summary
An estimated 3% of the world�s population is infected with hepatitis C virus (HCV). With low spontaneous clearance rates and often a poor response to treatment many infected individuals will develop long term complications from HCV. Recent studies have identified a genetic variant that is significantly associated with spontaneous viral clearance of HCV and response to treatment for HCV. We propose to further investigate the functional basis for the effect of this human genotype on drug response.
Synthetic Approaches For Dissection Of The Signalling Response Heterogeneity And Targeted Therapeutic Use Of Type-1 Interferons
Funder
National Health and Medical Research Council
Funding Amount
$375,974.00
Summary
Type-1 interferons have been used to treat at least 14 diseases, including cancer, hepatitis and multiple sclerosis. Differing success of treatment and serious side effects felt by patients, however, have limited use of these otherwise powerful therapies. I aim to better understand the responses different cells have to interferons to improve their utility in the clinic. Also, I will develop approaches to target interferons to the site of disease, reducing the side effects felt by patients.
Role Of PLZF In Regulating The Interferon Response
Funder
National Health and Medical Research Council
Funding Amount
$531,696.00
Summary
The Interferon (IFN) pathway is essential for immune defense against pathogens in vertebrates. IFNs both protect and alert cells about viral, bacterial, and other immune assaults and promote a cellular antiviral state, reduce proliferation, or induce apoptosis depending on the cell type and environment. Based on these properties, IFNs have been used clinically against a variety of diseases including viral infections, immunomodulatory disorders and hematologic and solid tumors including renal cel ....The Interferon (IFN) pathway is essential for immune defense against pathogens in vertebrates. IFNs both protect and alert cells about viral, bacterial, and other immune assaults and promote a cellular antiviral state, reduce proliferation, or induce apoptosis depending on the cell type and environment. Based on these properties, IFNs have been used clinically against a variety of diseases including viral infections, immunomodulatory disorders and hematologic and solid tumors including renal cell carcinoma. However, the factors determining outcome of IFN treatment, remain to be determined. We have identified a subset of interferon stimulated genes whose sustained expression was found to correlate with heightened antiviral sensitivity of renal cell carcinoma cell lines to IFN. Many of these genes were found to have binding sites for the transcriptional repressor promyleocytic zinc finger protein (PLZF). PLZF was first identified in a subset of Acute Promyelocytic Leukemia patients and is involved in maintenance of erythroid lineage stem cells and spermatogonial stem cells in male mice. PLZF has not previously been implicated in the IFN response. Accordingly, we investigated the expression of interferon stimulated genes and showed that increased expression of immune related genes depends on PLZF expression. PLZF was also found to directly associate with binding sites in promoters of interferon stimulated genes and that this requires histone deacetylation. Thus, we uncovered a novel function for PLZF in enhancement of IFN associated gene expression. We propose to test the hypothesis that PLZF is an essential component of the IFN response. As a corollary, we will also test whether PLZF expression can be linked to IFN responsiveness in renal cell carcinoma. These studies will establish the role of PLZF in the IFN response and define its utility in predicting IFN responsiveness in therapeutic applications.Read moreRead less
Identification Of Interferon Stimulated Genes That Limit HCV Replication And Predict Therapeutic Outcome
Funder
National Health and Medical Research Council
Funding Amount
$389,224.00
Summary
The only treatment for hepatitis C is Interferon-ribavirin combination therapy. Interferon works by stimulating the liver cells to produce antiviral proteins that can control hepatitis C virus replication, however we do not know which proteins are responsible. The aim of this proposal is to identify those proteins that can limit HCV replication using both a laboratory based and clinical approach and to identify markers that will predict treatment outcome.
Identification Of Molecular Signatures In Indigenous And Non-Indigenous Australians With Systemic Lupus Erythematosus To Enable A Precision Medicine Approach.
Funder
National Health and Medical Research Council
Funding Amount
$645,205.00
Summary
Lupus is an incurable illness, strikingly more prevalent and severe in Indigenous Australians. The biological explanation for this has, however, never been explored. Markers measurable in the blood number in the thousands. To discover new drugs, highly complex data analysis methods, known as bioinformatics, are required to analyse the ‘stack’ of these blood markers. This study will be a first in Indigenous Australians with lupus, and will help in patient selection for emerging drugs.