Characterisation Of The Key Role Played By The Persistent Phase Of Chlamydia Pneumoniae In Disease Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$286,320.00
Summary
Chlamydia pneumoniae is a relatively newly identified pathogen that is responsible for several respiratory conditions such as, pneumonia and chronic obstructive pulmonary disease and has been strongly linked to heart disesae. Serious disease is due to low grade chronic infections, but we do not understand how the bacterium causes these chronic diseases. This project will identify markers of chronic C. pneumoniae infections and relate these to the disease that results. Identifying these markers o ....Chlamydia pneumoniae is a relatively newly identified pathogen that is responsible for several respiratory conditions such as, pneumonia and chronic obstructive pulmonary disease and has been strongly linked to heart disesae. Serious disease is due to low grade chronic infections, but we do not understand how the bacterium causes these chronic diseases. This project will identify markers of chronic C. pneumoniae infections and relate these to the disease that results. Identifying these markers of chronic disease should lead to improved methods of disease control, including new diagnostic tests, vaccines and new drug therapies.Read moreRead less
Determinants Of Cytomegalovirus Salivary Gland Persistence
Funder
National Health and Medical Research Council
Funding Amount
$566,308.00
Summary
Human cytomegalovirus (HCMV) persists for extended periods in the salivary gland, an organ of viral transmission. It is not clear how the virus avoids immune mediated control in this tissue. This aspect of viral pathology will be assessed in a mouse model using two strains of murine CMV which exhibit marked differences in salivary gland persistence. The role of tissue tropism (inhibition of apoptosis), viral immune evasion and host immunity in salivary gland persistence will be studied.
This program application seeks to draw on the skills of a world leading group of Australian researchers to bring novel HIV vaccine designs to clinical trials, improve vaccine design and create new opportunities for commercialisation. The Chief Investigators, Prof David Cooper, Prof Peter Doherty (Nobel Prize winner), A-Prof Stephen Kent and Prof Ian Ramshaw, have achieved major scientific developments including: innovative collaborative clinical trials, cutting edge research in T cell immunology ....This program application seeks to draw on the skills of a world leading group of Australian researchers to bring novel HIV vaccine designs to clinical trials, improve vaccine design and create new opportunities for commercialisation. The Chief Investigators, Prof David Cooper, Prof Peter Doherty (Nobel Prize winner), A-Prof Stephen Kent and Prof Ian Ramshaw, have achieved major scientific developments including: innovative collaborative clinical trials, cutting edge research in T cell immunology, the establishment of the only PC3-level nonhuman primate facility in the Southern hemisphere, T cell immunogenicity of the DNA-viral vector prime-boost vaccine regimens and ground-breaking research on cytokine co-expressing viral vector vaccines. The Principle Investigators also have a record of substantial achievement in relation to HIV and T cell biology as well as novel vaccination technologies. There is a strong history of successful collaboration among this group leading to the award of major NIH funding.Read moreRead less
CAPLA Study: Catheter Ablation For Persistent Atrial Fibrillation. A Multicentre Randomised Study Of Pulmonary Vein Antral Isolation (PVAI) Alone Vs PVAI With Posterior Left Atrial Wall Isolation (PWI)
Funder
National Health and Medical Research Council
Funding Amount
$124,676.00
Summary
Atrial fibrillation (AF) is a common heart rhythm abnormality that affects quality of life with added health care costs. A minimally invasive procedure called catheter ablation (CA) is effective in controlling simple AF (paroxysmal AF) but the best ablation strategy to control a more resistant form of AF (Persistent AF) is unknown. This trial has been designed to address this key gap in knowledge by assessing if adding specific additional ablation to CA will improve outcomes.
Exposure And Risks From Persistent Organic Pollutants Through Consumption Of Traditional Seafood
Funder
National Health and Medical Research Council
Funding Amount
$322,042.00
Summary
For many coastal Aboriginal and Torres Strait Islander people, local marine resources provide an important and integral aspect of the communities' diet, culture and traditions. The health benefits associated with seafood consumption have been well documented. On the other hand, many environmental contaminants accumulate in the marine environment. In particular persistent organic pollutants (POPs) have the potential to accumulate to elevated levels in the marine food chain, including humans. Cons ....For many coastal Aboriginal and Torres Strait Islander people, local marine resources provide an important and integral aspect of the communities' diet, culture and traditions. The health benefits associated with seafood consumption have been well documented. On the other hand, many environmental contaminants accumulate in the marine environment. In particular persistent organic pollutants (POPs) have the potential to accumulate to elevated levels in the marine food chain, including humans. Consumption of food contaminated with POPs can pose a risk of causing adverse health effects, including cancer, endocrine disruption, developmental and immunotoxic responses. Recent studies in Queensland have shown elevated concentrations of POPs, specifically dioxins, in the near shore marine environment. Concentrations present in dugong and turtle tissues were found to be among the highest reported compared to other marine biota worldwide. These species represent an integral part of the traditions and diet for many coastal Aboriginal and Torres Strait Islander communities. However, to date no information on exposure to these compounds from locally sourced seafood exists in Australia. The proposed study will redress this lack of information and provide an understanding of the risks associated with the consumption of traditional seafood from local contaminated areas. In collaboration with the Quandamooka community, Moreton Bay in South East Queensland this will provide a case study with the objectives of: 1. Assessing the qualitative and quantitative risks associated with consumption of traditional and contemporary seafood sourced from local contaminated areas. 2. Providing communities with a thorough understanding of food contamination and building internationally competitive capacity in Australian Indigenous researchers. 3. Develop risk management options that allow informed decisions making on POP exposure and are acceptable to the community.Read moreRead less
Human cytomegalovirus (HCMV) is a classic example of a group of herpes viruses, which is found universally throughout all geographic locations and socioeconomic groups, and infects 50% of adults in developed countries. HCMV infection is important to certain high-risk groups. Major areas of concern are: (1) the risk of infection to unborn baby during pregnancy, (2) the risk of infection to people who work with children, and (3) the risk of infection to immunocompromised persons (e.g. organ transp ....Human cytomegalovirus (HCMV) is a classic example of a group of herpes viruses, which is found universally throughout all geographic locations and socioeconomic groups, and infects 50% of adults in developed countries. HCMV infection is important to certain high-risk groups. Major areas of concern are: (1) the risk of infection to unborn baby during pregnancy, (2) the risk of infection to people who work with children, and (3) the risk of infection to immunocompromised persons (e.g. organ transplant patients and HIV-infected individuals). Epidemiological studies have shown that 80%-90% of developing unborn babies who acquire congenital HCMV infection displays a variable pattern of pathological sequelae within the first few years of life that may include hearing loss, vision impairment and mental retardation. There is an increasing argument that a reduction in HCMV load will have a significant effect on the sequelae associated with congenital HCMV infection. Indeed, vaccination provides the most practical modality of achieving such a reduction in HCMV load. To develop such a vaccine, formulation based on viral antigens that activate both protective cellular and humoral responses needs to be tested to assess its immunogenicity. No such vaccine is presently available for HCMV. In this application we have sought to develop a prophylactic vaccine and to test its efficacy in a immunocompetent transgenic mouse model and as well under conditions of immunosuppression (CD4 T cell deficient). The overall strategy is to use this prophylactic vaccine to stimulate the cellular (CD8+ and CD4+ T cells) and humoral responses against multiple HCMV antigens. This vaccine will be based on the novel chimeric polyepitope technology and exploits a novel replication deficient adenovirus expression system which has recently been approved for human use.Read moreRead less
Effects Of Natural Sequence Variation On Evasion Of Cytotoxic T Lymphocytes By Murine Cytomegalovirus.
Funder
National Health and Medical Research Council
Funding Amount
$553,167.00
Summary
Human cytomegalovirus persists for the life time of an infected person. It has many ways of achieving this, including interfering with the host immune response. This project seeks to explore this using a mouse model and murine CMV. Specifically we will focus on a set of viral genes that inhibit host recognition of virally infected cells. Sequence variation in these genes suggests that they function differently in different strains of virus: we will examine the consequences of this variation.
Title: Structure of hepadnaviral pre-genomic RNA. We aim to study the replication strategy of human hepatitis B virus (HBV), a member of the hepadnavirus family. Hepadnaviruses infect hepatocytes in the liver and are released in high numbers into the bloodstream. Infection is transmitted by blood or sexual contact. Hepadnaviruses cause acute and chronic infection with varying degrees of liver disease. The HBV DNA genome is formed by copying of a viral pre-genome made of RNA, into DNA. This proce ....Title: Structure of hepadnaviral pre-genomic RNA. We aim to study the replication strategy of human hepatitis B virus (HBV), a member of the hepadnavirus family. Hepadnaviruses infect hepatocytes in the liver and are released in high numbers into the bloodstream. Infection is transmitted by blood or sexual contact. Hepadnaviruses cause acute and chronic infection with varying degrees of liver disease. The HBV DNA genome is formed by copying of a viral pre-genome made of RNA, into DNA. This process is called reverse transcription and is performed by the viral polymerase. Reverse transcription occurs within viral nucleocapsids made of core antigen. After formation of the new viral DNA genome, nucleocapsids are enveloped in surface antigen and are released from the cell. It is assumed that 1 copy of HBV pre-genomic RNA is packaged within each viral nucleocapsid. However, members of the retrovirus family that have common evolutionary origins to hepadnaviruses and also replicate via reverse transcription, contain 2 copies of RNA. The human immunodeficiency virus (HIV), the AIDS virus, is a well-studied example. In HIV infection 2 RNA genomes are packaged into each nucleocapsid and form a dimeric RNA genome. The HIV RNA is able to fold into a series of stem loops that promote formation of dimers. During the reverse transcription step in HIV replication, the polymerase switches templates and forms new combined strains of virus. The project aims to determine if 2 copies of pre-genomic RNA are packaged into HBV nucleocapsids. HBV pre-genomic RNA is able to form stem loop structures similar to those in HIV and has the potential to form dimeric RNA. If 2 copies of HBV pre-genomic RNA are packaged this will allow us to redefine the viral replication strategy and to develop a greater understanding of the relationships between hepadnaviruses and retroviruses. The formation of dimers will also provide a mechanism for recombination between HBV strains.Read moreRead less
Molecular Mechanisms Of Persistence Of Mycobacterium Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$398,142.00
Summary
Mycobacterium tuberculosis is the bacterium that causes tuberculosis (TB. It infects about third of all people in the world and kills several million people each year. People with active TB spread the mycobacteria in aerosols from their breath. When another person inhales an infected aerosol the mycobacteria enter their lungs and establish a new infection. During the course of infection M. tuberculosis is exposed to a variety of harsh environments inside the lungs which normally kill other bacte ....Mycobacterium tuberculosis is the bacterium that causes tuberculosis (TB. It infects about third of all people in the world and kills several million people each year. People with active TB spread the mycobacteria in aerosols from their breath. When another person inhales an infected aerosol the mycobacteria enter their lungs and establish a new infection. During the course of infection M. tuberculosis is exposed to a variety of harsh environments inside the lungs which normally kill other bacteria. M. tuberculosis is able to survive and adapt to those harsh environments. M. tuberculosis has an especially thick and tough cell wall which protects it. M. tuberculosis can adapt to the environments it encounters in a patient by changing their cell walls. The wall also protects mycobacteria from chemicals so it is resistant to many common antibiotics. There are some drugs to treat TB however M. tuberculosis is building up resistance to those drugs so we need to find new ones We will determine how mycobacteria synthesize their special cell wall and how they adapt during an infection. If we know how the details of how M. tuberculosis protects itself then we can find potential weakness which could be targets for the development of new drugs to treat TB.Read moreRead less
The Impact Of Interplays Between Viral Immune Evasion Proteins And Host Cell-surface Receptors On Viral Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$482,710.00
Summary
Herpesviruses can cause infections that persist for the lifetime of the individual. These viruses have evolved a range of mechanisms to evade the host's immune response that would otherwise eliminate them. One member of the herpesvirus family that is replete with methods for avoiding the immune response is cytomegalovirus. This virus, while not causing symptoms in healthy people, is a significant cause of disease and mortality in indivuals who are immunosuppressed such as AIDS patients or people ....Herpesviruses can cause infections that persist for the lifetime of the individual. These viruses have evolved a range of mechanisms to evade the host's immune response that would otherwise eliminate them. One member of the herpesvirus family that is replete with methods for avoiding the immune response is cytomegalovirus. This virus, while not causing symptoms in healthy people, is a significant cause of disease and mortality in indivuals who are immunosuppressed such as AIDS patients or people undergoing transplantation, or in neonates who have poorly developed immune responses. In the current project we will explore how virally encoded proteins that bind to cell surface receptors expressed on a class of immune effector cell called the Natural Killer (NK) cell, can interfere with the functions of these cells. We will seek to define the NK cell proteins that are specifically bound by these viral proteins and also make deletion mutants of these viral genes to assess what effect knocking out these genes has on virus-caused disease. These studies will provide important insights into novel mechanisms of viral immune evasion and may provide insights into how therapies could be developed that interfere with the functions of these viral proteins.Read moreRead less