The Characterisation Of Deubiquitinating Enzyme A (DUBA) In The Control Of Innate And Adaptive Immune Signalling.
Funder
National Health and Medical Research Council
Funding Amount
$396,041.00
Summary
In response to viruses, the immune system produces interferons. Interferons fight infections but can also contribute to autoimmune diseases, where the body mistakenly attacks itself. Production of interferons is regulated by DUBA. Thus DUBA is an attractive target for therapies against viruses or autoimmune diseases. To achieve this, it is important to understand not only the mechanism of action of DUBA, but also what other roles DUBA may play in the immune system. We can study these in mice.
Understanding The Mechanisms Of Cytomegalovirus Induced Immunosuppression: Relevance To Viral Immunotherapies
Funder
National Health and Medical Research Council
Funding Amount
$467,310.00
Summary
Cytomegalovirus (CMV), measles and human immunodeficiency virus (HIV) are the three main human pathogens known to induce immunosuppression. The down-regulation of immune responses that characterizes a state of immunosuppression imparts the infecting pathogens the opportunity to escape immune surveillance and thus maximizes their chances to survive within their host, to replicate and be transmitted as required. The generalized immunosuppression caused by viral infection is often associated with s ....Cytomegalovirus (CMV), measles and human immunodeficiency virus (HIV) are the three main human pathogens known to induce immunosuppression. The down-regulation of immune responses that characterizes a state of immunosuppression imparts the infecting pathogens the opportunity to escape immune surveillance and thus maximizes their chances to survive within their host, to replicate and be transmitted as required. The generalized immunosuppression caused by viral infection is often associated with secondary infections with unrelated viral and-or bacterial pathogens, and as such represents a serious clinical problem. In humans, cytomegalovirus infection can cause tissue damage in normal individuals and may cause severe disease and even mortality in individuals with immature or compromised immune systems, such as newborns, AIDS patients, transplant recipients and patients undergoing chemotherapy. The severe complications that occur in the latter group of patients result from the combined effects of pre-existing and viral induced immunosuppression that often lead to severe secondary opportunistic infections. In transplant recipients however, CMV induced immunosuppression, in the absence of secondary infections, can be beneficial and has been associated with improved transplant outcome. The central aim of the work in the current proposal is to investigate the cellular and viral mechanisms involved in cytomegalovirus induced immunosuppression. The proposed studies will improve our understanding of viral interference with host immune responses and hence will be relevant to understanding the pathogenesis of CMV infection in humans and more importantly will provide critical insights into the rational design of suitable antiviral drugs and vaccines.Read moreRead less
Effective Immunotherapy For HPV Associated Cervical Cancer Precursor Lesions
Funder
National Health and Medical Research Council
Funding Amount
$482,640.00
Summary
Vaccines to prevent cervical cancer are currently being developed. These will be used to prevent infection with the causal virus, papillomavirus. However, there are very many people world wide who already have papillomavirus infection, which could turn into cancer at any point over the next 30 years. Therefore, there is a need for a vaccine that could be given along with the preventative vaccine, which would treat existing infections. This study addresses the characteristics of the immune respon ....Vaccines to prevent cervical cancer are currently being developed. These will be used to prevent infection with the causal virus, papillomavirus. However, there are very many people world wide who already have papillomavirus infection, which could turn into cancer at any point over the next 30 years. Therefore, there is a need for a vaccine that could be given along with the preventative vaccine, which would treat existing infections. This study addresses the characteristics of the immune response required to treat existing papillomavirus infections, since this is not currently known.Read moreRead less
An Analysis Of The Lyn Tyrosine Kinase In The Regulation Of Hematopoiesis And Tumourigenesis.
Funder
National Health and Medical Research Council
Funding Amount
$381,000.00
Summary
The Lyn kinase is an enzyme that is involved in relaying information across the cell membrane. It is a member of a family of genes that have been implicated in tumour development. Lyn is expressed in blood cells and it is involved in a variety of immunological responses. To further our understanding of the role of this enzyme in the context of the whole animal, we have generated two strains of mice, one that is unable to make Lyn protein (Lyn-deficient mice) and one that expresses an activated f ....The Lyn kinase is an enzyme that is involved in relaying information across the cell membrane. It is a member of a family of genes that have been implicated in tumour development. Lyn is expressed in blood cells and it is involved in a variety of immunological responses. To further our understanding of the role of this enzyme in the context of the whole animal, we have generated two strains of mice, one that is unable to make Lyn protein (Lyn-deficient mice) and one that expresses an activated form of the Lyn enzyme (Lyn-up mice). Our previous studies have shown that Lyn-deficient mice have enhanced blood cell formation (hematopoiesis) and develop white blood cell tumours with age, whereas Lyn-up mice show no propensity to develop tumours. In this study we will examine in detail the role that Lyn plays in blood cell formation and tumourigenesis, and we will identify the pathways that underlie the phenotypes in Lyn-deficient mice. On completion of these studies we will have catalogued the molecules and pathways regulated by Lyn, and have an understanding of how Lyn functions in regulating development of specific populations of blood cells, and in suppressing or promoting tumour development.Read moreRead less
A Novel Viral Modifier Of TNF Family Receptor Signalling: Elucidation Of Mechanisms Of Action
Funder
National Health and Medical Research Council
Funding Amount
$453,727.00
Summary
Over millions of years, viruses have evolved a great number of strategies to allow them to subvert the effectiveness of the host response. We have discovered that one of these viral strategies seems designed to block the synthesis of an important anti-viral factor, called tumour necrosis factor. In this project, we aim to work out how the viral factor blocks tumour necrosis factor production inside the cell, at the level of the molecules involved. The second aspect of this project concerns the i ....Over millions of years, viruses have evolved a great number of strategies to allow them to subvert the effectiveness of the host response. We have discovered that one of these viral strategies seems designed to block the synthesis of an important anti-viral factor, called tumour necrosis factor. In this project, we aim to work out how the viral factor blocks tumour necrosis factor production inside the cell, at the level of the molecules involved. The second aspect of this project concerns the identification of the types of cells and responses which the viral factor acts upon to manipulate the host response. We reason that this information will improve our understanding of how tumour necrosis factor production is regulated and the significance of this type of response in virus infection and physiology, more generally. The application of this research will be to aid the design of better drugs for the treatment of many conditions where tumour necrosis factor production contributes significantly to pathology, eg rheumatoid arthritis and autoimmunity. In some conditions, it may be a therapeutic advantage to selectively turn on tumour necrosis factor, eg for treatment of infections or cancer.Read moreRead less