Progression Of Influenza Virus Within The Respiratory Tract
Funder
National Health and Medical Research Council
Funding Amount
$513,716.00
Summary
We are exploring how influenza virus moves down the respiratory tract after infecting the nose. We have identified a component of mouse saliva that can halt the progression from the nose to the trachea and lungs and will determine how it binds to the virus to stop infection. We will also examine how human and highly lethal avian viruses move from the upper respiratory tract to other organs in the mouse and also in the ferret, which is a much better model for mimicking what happens in man.
A Novel Strategy Targeting Quorum Sensing Molecules And Catalase Function To Block Pseudomonas Aeruginosa Lung Infection
Funder
National Health and Medical Research Council
Funding Amount
$451,118.00
Summary
Pseudomonas aeruginosa causes serious infections, particularly in those with Cystic Fibrosis, immunocompromise, serious burns or long term catheters. We will use a unique strategy to target virulence factors that will assist in clearing acute infection, prevent establishment of new chronic infections, and potentially reduce severity of established chronic infections. It has the potential to make antibiotic therapy more effective and lessen the extent of antibiotic therapy required.
Is The Excess Mortality Amongst Tuberculosis Survivors Explained By Chronic Pulmonary Aspergillosis? Investigating Burden, Diagnosis, And Therapy
Funder
National Health and Medical Research Council
Funding Amount
$645,205.00
Summary
Chronic pulmonary aspergillosis (CPA) is a serious lung infection due to the mould Aspergillus. It affects people with damaged lungs, such as those who have had tuberculosis. In Vietnam, TB is extremely common, and there should be many cases of CPA. However, because diagnostic facilities are poor, CPA is often wrongly labelled as failed TB treatment, and patients receive the wrong therapy. My research will determine the size of the problem in Vietnam and how best to address it.
Role Of Complement Factor H And Related Proteins In Regulating Complement Activation And Microbial Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$377,036.00
Summary
A group of proteins in blood called Complement are activated in the presence of foreign cells or organisms and this generally results in their destruction. It is important to direct this destructive activity against foreign and not self tissue. This is achieved by a further family of proteins, including factor H, which regulate complement activity and how these proteins work is the principal focus of this project. There are many diseases in which damage results from inadvertent complement damage ....A group of proteins in blood called Complement are activated in the presence of foreign cells or organisms and this generally results in their destruction. It is important to direct this destructive activity against foreign and not self tissue. This is achieved by a further family of proteins, including factor H, which regulate complement activity and how these proteins work is the principal focus of this project. There are many diseases in which damage results from inadvertent complement damage and the regulatory proteins have therapeutic potential in this area. In addition many bacteria and other microorganisms, which should be destroyed by complement, escape by binding regulatory proteins. Understanding how this is achieved may reveal new targets for vaccine development. Knowledge of how the production of factor H and related proteins will help understand how inflammation occurs and how it might be controlled.Read moreRead less
Quorum Sensing Signal Molecule Modulation Of Immunity: Role In Host Responses To P. Aeruginosa Lung Infection
Funder
National Health and Medical Research Council
Funding Amount
$251,014.00
Summary
Pseudomonas aeruginosa is a bacterium that causes serious infections in humans, particularly those with Cystic Fibrosis, or who are immunocompromised, suffering serious burn injuries or have long term catheters. This study will investigate how P. aeruginosa may be able to increase its virulence by producing molecules known as Quorum Sensing Signal Molecules (QSSM). We believe the production of these QSSMs by this bacterium enables them to affect how the host responds by affecting their immune sy ....Pseudomonas aeruginosa is a bacterium that causes serious infections in humans, particularly those with Cystic Fibrosis, or who are immunocompromised, suffering serious burn injuries or have long term catheters. This study will investigate how P. aeruginosa may be able to increase its virulence by producing molecules known as Quorum Sensing Signal Molecules (QSSM). We believe the production of these QSSMs by this bacterium enables them to affect how the host responds by affecting their immune system. We will be investigating how this QSSM may suppress immunity and what influence this has on both the severity of infection and the potential for development of chronic infection. The study will first of all determine where the QSSM exerts its effects (that is, can it escape from the site of infection to affect other host sites) and this will direct us in how we may learn more about the way it can affect the host during an infection. We will investigate the direct affects of QSSM on acute and chronic types of P. aeruginosa lung infection and then from this, determine if the outcome exacerbates a subsequent infection. The work is significant in that a knowledge and understanding of these virulence factors will assist in the design of better therapeutic and prophylactic strategies for both prevention of infection in susceptible individuals and treatment of those that suffer from chronic infection.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
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
Comparative Expression Studies To Identify Cellular Factors Promoting Hendra Virus Replication For A Comprehensive Understanding Of Hendra Virus Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$374,619.00
Summary
Hendra virus (HeV) is an emerging pathogen indigenous to fruit bats. HeV is associated with limited outbreaks with high mortality in domesticated animals and humans. To advance the understanding of HeV-related pathogenesis, we will perform comparative studies in bat and human cell lines to recognise differences in virus-host cell interactions leading to a comprehensive understanding of the HeV life cycle and pathogenesis.
The pathogen Cryptococcus neoformans is responsible for hundreds of thousands of deaths annually. If the infection is survived, relapse caused by evolved forms of the original infecting strain is common. Our research has uncovered similar genetic changes in isolates from unrelated patients that implicate epigenetic processes in relapse and reveal potential vulnerabilities of the pathogen. The proposed work is to investigate these changes to assist in our antifungal drug development efforts.
I am an immunologist studying host immune responses during malaria and visceral leishmaniasis, two important human infectious diseases. I aim to identify immune responses that promote safe and effective control of parasite growth and distinguish them from