The Effect Of Innate Immune Responses On The Induction Of Protective Immunity In Murine Typhoid Fever
Funder
National Health and Medical Research Council
Funding Amount
$136,500.00
Summary
Salmonella are important pathogens of humans causing diseases ranging from gastroenteritis, typhoid fever to arthritis. Like most if not all infections, the early interaction between the host and the bacterium is characterised by very non-specific symptoms. These non-specific symptoms arise because the so-called innate immune system is activated by the infection. The purpose of this grant is to establish whether these non-specific symptoms, caused by the release of immunological homrones called ....Salmonella are important pathogens of humans causing diseases ranging from gastroenteritis, typhoid fever to arthritis. Like most if not all infections, the early interaction between the host and the bacterium is characterised by very non-specific symptoms. These non-specific symptoms arise because the so-called innate immune system is activated by the infection. The purpose of this grant is to establish whether these non-specific symptoms, caused by the release of immunological homrones called cytokines, are essential to the development of an effective immune response which can protect against subsequent re-infection. This study has important implications for vaccines, of our understanding of how bacteria cause disease, and the role-capacity of the innate immune system in the development of immunity.Read moreRead less
Argonaute Proteins In The Mammalian Antiviral Response
Funder
National Health and Medical Research Council
Summary
Viruses are the most abundant infectious agents on earth, and the diseases caused by them are a constant threat and cause of mortality worldwide. Awarded the Nobel Prize for Medicine in 2006, RNA interference (RNAi) is a natural process that plants use to attack viruses. Humans possess all of the tools for RNAi, but whether it is used for antiviral defense is unknown. This study aims to uncover this immune process which will open new avenues to treat virus infections, such as influenza and HIV.
This project examines how high fat diets affect inflammation and asthma outcomes. Research regarding the relationship between asthma and obesity is inconclusive. This project examines high fat intake as an initiator of both these conditions. We explore statins as a treatment for diet-induced inflammation. By increasing our understanding of how fat affects inflammation, we will be able to plan a dietary approach to improve asthma outcomes.
Defining The Molecular Effectors And Regulators Of Anti-viral Immune Responses
Funder
National Health and Medical Research Council
Funding Amount
$447,750.00
Summary
In humans, cytomegalovirus infection can cause severe disease and may even be fatal in individuals with immature or compromised immune systems, such as newborns, AIDS patients, transplant recipients and people treated with chemotherapeutic drugs. The majority of healthy individuals however can clear the infection with minimal disease. The ability of cytomegalovirus to cause disease is increased in the absence of effective immune responses which would normally clear the virus before illness occur ....In humans, cytomegalovirus infection can cause severe disease and may even be fatal in individuals with immature or compromised immune systems, such as newborns, AIDS patients, transplant recipients and people treated with chemotherapeutic drugs. The majority of healthy individuals however can clear the infection with minimal disease. The ability of cytomegalovirus to cause disease is increased in the absence of effective immune responses which would normally clear the virus before illness occurs. Understanding the role of specific mediators of anti-viral immune responses is therefore of paramount importance in establishing the guidelines for the design of more effective anti-viral therapies. The mouse model of cytomegalovirus infection provides a unique system to dissect the roles of specific components of the immune response during the course of viral infection. Our previous studies have shown that anti-viral immune responses are complex and involve a multitude of players. The central aim of the work in the current proposal is to establish the precise contribution of specific molecular effectors and regulators of anti-viral immune responses and define their relevance during the different stages of viral infection. Hence, the results of these studies will be relevant to understanding the pathogenesis of cytomegalovirus infection in humans and more importantly will provide critical insights into the rational design of improved antiviral drugs and vaccines. Since the molecules and cells under investigation are also known to play a crucial role in immune responses that control tumour growth and transplant survival, the proposed studies will provide valuable insight towards the development of new therapies for pathologies associated not only with cytomegalovirus infection, but also with the conditions named above.Read moreRead less
The Role Of 14-3-3 Proteins In Regulating The Innate Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$517,989.00
Summary
The immune response is the body's defense system. It's malfunction leads to many diseases such as immune deficiency, asthma and cancer. Thus, it is important to find genes controlling immunity. Significantly, mammals have amazing similarities with flies, in terms of genes controlling immunity. We have found a new regulator of fly immunity and will define how this gene functions in the immune system. This project will identify potential points of intervention for treating immune system disorders.
The Role Of Mal In Toll-like Receptor Signal Transduction Of The Pro-inflammatory Response.
Funder
National Health and Medical Research Council
Funding Amount
$472,500.00
Summary
Sepsis kills more people per year than the cancers of the breast, colon, prostate and pancreas combined. Sepsis occurs in 1 of 50 hospital admissions and is the leading cause of death n intensive care units. The instance of sepsis has doubled in the last decade and is expected to increase. One of the major causes of sepsis si lipopolysaccharide (LPS), the main constituent of gram-negative bacteria's cell wall, and the prototypic inducer of the pro-inflammatory response of the innate immune syste ....Sepsis kills more people per year than the cancers of the breast, colon, prostate and pancreas combined. Sepsis occurs in 1 of 50 hospital admissions and is the leading cause of death n intensive care units. The instance of sepsis has doubled in the last decade and is expected to increase. One of the major causes of sepsis si lipopolysaccharide (LPS), the main constituent of gram-negative bacteria's cell wall, and the prototypic inducer of the pro-inflammatory response of the innate immune system. Dysregulation of the pro-inflammatory response can lead to sepsis. Recently, the mammalian receptor for LPS was found to be Toll-like receptor (TLR)-4, the activation of which activates a signal transduction pathway that initiates the pro-inflammatory response. We have previously shown a key role for an adapter protein called Mal in mediating signal transduction pathways upon activation of TLR-4. Interaction of Mal with a key signal transduction mediator called TRAF6 has been shown to induce the activation of the pro-inflammatory response. Furthermore, Mal has been found to undergo degradation which may indicate a means of regulating the continued activation of the pro-inflammatory pathway. This research program will investigate the role of Mal in mediating signal transduction in TLR activated macrophages, key responsive cells of the innate immune system to microbial infection. A greater understanding of these processes will assist in the development of therapeutics to alleviate the consequences of microbial-induced inflammation, including chronic inflammatory diseases and sepsis.Read moreRead less
Immunopathological Role Of Monocyte-macrophages In Flavivirus Encephalitis.
Funder
National Health and Medical Research Council
Funding Amount
$445,011.00
Summary
Viral encephalitis is a life-threatening infection of the brain for which there are no reliable treatments. White cells called monocytes enter the brain from the blood and although important in the immune response that destroys the virus, can also damage the brain. Our work focuses on determining how monocytes migrate into the brain in viral infection, what functions they have once inside the brain, and how to exclude a certain types of monocytes that we have found to be particularly damaging.