Functional Analyses Of The Major Merozoite Surface Protein Of Malaria Parasites
Funder
National Health and Medical Research Council
Funding Amount
$70,285.00
Summary
In this project we aim to learn about the function of one of the leading malaria vaccine candidates, merozoite surface protein 1 (MSP-1). Although a promising candidate, little is known about the role of this protein in the invasion by parasites of red blood cells or of the likelihood that the parasites will adapt to avoid vaccines based on MSP-1. To address these issues we propose to use the powerful new technology of parasite transfection, that is the ability to insert DNA into parasites to sp ....In this project we aim to learn about the function of one of the leading malaria vaccine candidates, merozoite surface protein 1 (MSP-1). Although a promising candidate, little is known about the role of this protein in the invasion by parasites of red blood cells or of the likelihood that the parasites will adapt to avoid vaccines based on MSP-1. To address these issues we propose to use the powerful new technology of parasite transfection, that is the ability to insert DNA into parasites to specifically alter its genetic code. We have pioneered this technology and have developed many of the most effective tools for the process. Insight gained from these studies is likely to influence significantly the design and potential uses of MSP-1 as a vaccine to control malaria.Read moreRead less
Relationship Between Periodontal Disease And Rheumatoid Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$520,657.00
Summary
Periodontal (gum) disease and rheumatoid arthritis are two of the most common chronic inflammatory diseases affecting humans. These two diseases have remarkably similar patterns of tissue destruction. It is possible that individuals with chronic periodontitis may prime or predispose individuals prone to developing rheumatoid arthritis. Treatment of periodontal disease may help reduce the severity of rheumatoid arthritis.
Cellular Activation And Apoptosis In Response To Foreign Cytoplasmic DNA
Funder
National Health and Medical Research Council
Funding Amount
$496,446.00
Summary
Viruses are simple organisms. They grow within cells, needing host cell proteins for their replication. Viruses have only a few proteins of their own, and evolve rapidly to change these. It is therefore challenging for the immune system to identify viral infections. Recently it has been recognised that the genetic material of viruses (DNA or RNA) is detected by the immune system. A novel pathway for recognition of viral double stranded DNA is emerging. The genetic material of mammalian cells (DN ....Viruses are simple organisms. They grow within cells, needing host cell proteins for their replication. Viruses have only a few proteins of their own, and evolve rapidly to change these. It is therefore challenging for the immune system to identify viral infections. Recently it has been recognised that the genetic material of viruses (DNA or RNA) is detected by the immune system. A novel pathway for recognition of viral double stranded DNA is emerging. The genetic material of mammalian cells (DNA) is found within the membrane-bound nucleus of the cell. The presence of DNA outside the nucleus in the cytoplasm is abnormal, and is detected as an indication of viral infection. This causes either death of the cell, or activation to produce anti-viral molecules. We have identified a protein from the cytoplasm of cells which binds specifically to DNA. This protein, X is found in association with foreign DNA within 5 minutes of it being introduced into the cell. In this project we propose to confirm that X recognises foreign DNA and initiates cellular activation or death. Other molecules to which X binds during this process will be identified. This project is relevant to a number of problems in health and disease as well as biotechnology. In both gene therapy and biotechnology, DNA is introduced into cells in order to allow those cells to make specific proteins. The cell sees the introduced DNA as a potential viral infection, and it responds in ways which limit the production of the desired proteins. Lupus is an autoimmune disease with high levels of DNA in circulation. X is proposed as a protein involved lupus in mouse models. We suggest that DNA taken up by cells is recognised by X and this contributes to the disease. Understanding the means by which DNA is recognised in the cytoplasm may allow the development of much more efficient processes for gene therapy and protein production in biotechnology, and more effective lupus and antiviral therapies.Read moreRead less
Identification Of Type III Effectors In Salmonella
Funder
National Health and Medical Research Council
Funding Amount
$555,325.00
Summary
Salmonella is a major cause of disease across the world. In order to cause disease, Salmonella injects certain molecules into our own human cells to reprogramme them to promote Salmonella infection. This work aims to identify a large proportion of those molecules injected by Salmonella. Once identified, a more complete understanding of exactly how Salmonella reprogrammes our cells will be possible, enabling new avenues for therapeutics.
Development Of An Immunotherapy Against Kgp Of Porphyromonas Gingivalis
Funder
National Health and Medical Research Council
Funding Amount
$495,710.00
Summary
Chronic periodontitis is an inflammatory disease of the supporting tissues of the teeth associated with specific bacteria, which results in the destruction of tooth support and ultimately leads to tooth loss. This project aims to develop an immunotherapy against the major virulence factor produced by bacteria associated with the disease. The immunotherapy will be evaluated in animal models of disease.
Cytoplasmic DNA As A Danger Signal For Mammalian Cells
Funder
National Health and Medical Research Council
Funding Amount
$592,661.00
Summary
DNA in mammalian cells is contained within a structure known as the nucleus. The presence of DNA outside the nucleus in the cytoplasm of the cell is a sure sign that something is wrong, and may indicate the presence of a viral invader. In this case, the cell initiates anti-viral responses, including production of anti-viral proteins and death of the infected cell to stop replication of the virus. Lack of proper control of these responses may contibute to the autoimmune disease lupus.
Functional Characterisation Of The SseK/NleB Family Of Type III Secreted Effectors In Salmonella And E. Coli
Funder
National Health and Medical Research Council
Funding Amount
$510,183.00
Summary
Salmonella and E. coli cause enteritis and diarrhoea in a large proportion of the world's population including Australia. Certain strains of Salmonella also cause a more serious disease called typhoid fever. Together, diseases caused by Salmonella and E. coli are a major cause of illness and death. In order to cause disease Salmonella and E. coli use a specialised apparatus that functions like a needle and syringe to inject Salmonella proteins into human cells. These proteins that are injected i ....Salmonella and E. coli cause enteritis and diarrhoea in a large proportion of the world's population including Australia. Certain strains of Salmonella also cause a more serious disease called typhoid fever. Together, diseases caused by Salmonella and E. coli are a major cause of illness and death. In order to cause disease Salmonella and E. coli use a specialised apparatus that functions like a needle and syringe to inject Salmonella proteins into human cells. These proteins that are injected into human cells actively reprogram human cells to benefit the disease causing bacteria. We have recently discovered a new family of injected proteins and we aim to determine how these new proteins reprogram human cells and what this contributes to diarrhoea and typhoid fever. This information may lead to the development of more effective treatments for these important diseases.Read moreRead less
Links Between Inflammatory Activity, Autoantibodies, And Cardiovascular Disease In Patients With SLE.
Funder
National Health and Medical Research Council
Funding Amount
$32,003.00
Summary
People with lupus are at increased risk of heart attack and stroke. For women aged 30-44 the risk is as much as fifty times higher than in women without lupus. Only some of this risk is due to well known factors like high blood pressure and cholesterol. We are looking at other possible causes of heart attack and stroke in people with lupus - with blood tests and heart scans. We hope this will identify who is at risk and what can be done to prevent them from suffering a heart attack or stroke.
Determinant Spreading And The Role Of The MHC Class II Region In Systemic And Organ-specific Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$140,570.00
Summary
Autoimmune diseases are among the most important group of disorders affecting the adult population. In these diseases the immune system damages organs and tissues producing widespread pathology (systemic autoimmunity such as Lupus erythematosus) or localised disease (organ-specific autoimmunity such as insulin dependent diabetes). We understand very little about how and why the immune system attacks the body's own tissues. This study examines how antibodies and T lymphocytes are formed against c ....Autoimmune diseases are among the most important group of disorders affecting the adult population. In these diseases the immune system damages organs and tissues producing widespread pathology (systemic autoimmunity such as Lupus erythematosus) or localised disease (organ-specific autoimmunity such as insulin dependent diabetes). We understand very little about how and why the immune system attacks the body's own tissues. This study examines how antibodies and T lymphocytes are formed against components located inside cells of the body. The study involves genetically modifying mice by introducing key human genes which influence the development of autoimmunity. In this way the role of these human genes can be examined experimentally without having to work exclusively on patients. We also hope that these mice might be important in creating new models of celiac disease and insulin dependent diabetes. The proposed experiments should tell us how these genes contribute to the development of autoimmune disease. This understanding could be relevant devising treatments and interventions to prevent autoimmune diseases.Read moreRead less