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.
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.
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.
The Role Of PLZF In Regulating The Antiviral Activity Of Interferons
Funder
National Health and Medical Research Council
Funding Amount
$652,005.00
Summary
Interferons are the first line of defence against viral infection. We have shown that the transcription factor promyelocytic leukemia zinc finger protein (PLZF) is a novel regulator of the interferon response. Thus we hypothesize that PLZF is a critical component of the host's innate immune system. This study will provide new insights into the understanding of signal transduction mechanisms, as well as improve our ability to modulate sensitivity to interferon to protect against viral diseases.
Defining The Roles And Targeting Interferon-epsilon As A New Therapy For Influenza In Asthma And COPD
Funder
National Health and Medical Research Council
Funding Amount
$905,904.00
Summary
Influenza is a major cause of illness and death, especially in people with asthma and emphysema. There are issues with vaccines and current treatments are poorly effective. Effective treatments are urgently required. We have found a new immune factor, interferon-epsilon that is induced and used by influenza viruses to cause infection. We aim to understand how this occurs and to test new treatments for influenza that suppress interferon-epsilon, in healthy and susceptible individuals.
Targeting Disease-initiating Cells In Myeloproliferative Neoplasms
Funder
National Health and Medical Research Council
Funding Amount
$477,170.00
Summary
The myeloproliferative neoplasms (MPN) are a related group of blood disorders. Despite the advent of targeted therapies, patients have significant ongoing morbidity, mortality and financial cost. A key reason underlying the persistence of disease is the presence of a stem cell pool that is resistant to targeted therapy. Clinical data has suggested that interferon may target these disease stem cells. We propose to use in vivo, validated disease models to investigate the role of interferon in MPN.
Tumour Induced Innate Immune Responses That Control Breast Cancer Metastases
Funder
National Health and Medical Research Council
Funding Amount
$596,164.00
Summary
The mechanisms of breast cancer spread to bone are largely unknown. We have found that cross-talk between tumour cells and the immune system exists to induce anti-tumour immune responses. By decreasing the release of proteins known to activate immune responses (type I interferons), tumour cells can hide from such responses and spread to tissues such as bone. We aim to identify the immune responses activated by type I IFN and if restoration of these pathways can block breast cancer spread to bone ....The mechanisms of breast cancer spread to bone are largely unknown. We have found that cross-talk between tumour cells and the immune system exists to induce anti-tumour immune responses. By decreasing the release of proteins known to activate immune responses (type I interferons), tumour cells can hide from such responses and spread to tissues such as bone. We aim to identify the immune responses activated by type I IFN and if restoration of these pathways can block breast cancer spread to bone.Read moreRead less
Hepatitis C affects a quarter of a million Australians, causing insidious but progressive liver disease which culminates in liver failure or cancer. There is no vaccine and prevention programs have limited effectiveness, but new antiviral therapies now offer high rates of cure. This Program will evaluate strategies to improve the health of those affected and prevent new infections by better understanding of the virus and the body’s immune response, including scarring and liver cancer formation.
Protein-RNA interactions are critical in regulating the response to virus infections, and controlling the expression of genes involved in inflammation. Small interfering RNAs (siRNAs), important tools in gene discovery and potential therapy against virus infections and cancer, can activate the innate immune response. By understanding protein-siRNA interactions, we will gain new insights into the design of siRNAs for studying gene regulatory networks and for practical application in medicine.
Structural Characterisation Function Analyses Of Type I Interferon-receptor Interactions
Funder
National Health and Medical Research Council
Funding Amount
$517,989.00
Summary
The interferons are an essential component of the body's response to infectious and inflammatory disease and cancer. In order to design the best therapeutic approaches to modulate interferon activity, we need a defined understanding of how IFN binds to its receptor on target cells and activates its functions. This project will characterize these interactions in cells, mice and molecules with x-ray crystallography and the synchrotron to solve the structure and facilitate informed drug design.