Novel, High-throutyput Platform For Rapid Identification, Quantintation, Differential Diagnosis, And Resistance Testing
Funder
National Health and Medical Research Council
Funding Amount
$333,362.00
Summary
This proposal utilizes a newly invented process (multiplex tandem polymerase chain reaction, MT-PCR) to measure multiple (up to 100) genetic targets (eg RNA or DNA) in one sample. A range of different virus and bacterial genes can be detected, including those which make the influenza virus different (eg H1N1 or H5N1) and allow it to bypass vaccine immunity or resist drug therapy (due to neuraminidase inhibitor resistance). We will simultaneously target infections which are influenza-like (ILI) o ....This proposal utilizes a newly invented process (multiplex tandem polymerase chain reaction, MT-PCR) to measure multiple (up to 100) genetic targets (eg RNA or DNA) in one sample. A range of different virus and bacterial genes can be detected, including those which make the influenza virus different (eg H1N1 or H5N1) and allow it to bypass vaccine immunity or resist drug therapy (due to neuraminidase inhibitor resistance). We will simultaneously target infections which are influenza-like (ILI) or which might make influenza infection worse (eg staphylococcal pneumonia) as well as their resistance genes (eg MRSA). The test is rapid and automated and includes a specimen processing (DNA and RNA extraction) function that is being developed in parallel. We expect to be able to conduct high-throughput screening of multiple samples for a limited number of targets or conduct multiple tests on fewer specimens, simply by adjusting assay configuration. Measurement of the rise and fall in concentrations of influenza virus in infected persons will allow us to understand when they are no longer infectious to others, to predict when they are getting better or worse, and allow us to better understand the pattern of illness in people who are immunized against influenza or on drug therapy, or are in some other special category (eg immune compromise due to organ transplantation). While this will be able to be rolled out by our industry partners in the event of an influenza pandemic, it does not require an outbreak for successful development, and has value well beyond influenza diagnosis.Read moreRead less
Airway Inflammation In Asthma And Chronic Obstructive Pulmonary Disease
Funder
National Health and Medical Research Council
Funding Amount
$390,509.00
Summary
In chronic diseases of the airway such as asthma and airway narrowing due to cigarette smoking - chronic obstructive pulmonary disease (COPD), the airways show inflammation (increased numbers of cells and their products) and remodelling (increased thickness and scarring) which persist for many years, possibly indefinitely. The exact mechanisms by which inflammation persists in the airway wall in asthma and COPD are unknown. We and others have shown that greater numbers of memory T-lymphocytes (T ....In chronic diseases of the airway such as asthma and airway narrowing due to cigarette smoking - chronic obstructive pulmonary disease (COPD), the airways show inflammation (increased numbers of cells and their products) and remodelling (increased thickness and scarring) which persist for many years, possibly indefinitely. The exact mechanisms by which inflammation persists in the airway wall in asthma and COPD are unknown. We and others have shown that greater numbers of memory T-lymphocytes (T-cells) are present in the airway wall in asthma and COPD. T-cells orchestrate the processes involved in inflammation. We have hypothesised that the persistence of airway inflammation in asthma and COPD results from the proliferation of memory T-cells within the airway wall. Unlike na ve T-cells, memory T-cells have previously been stimulated and can easily be activated to proliferate and promote inflammation by other cells which are fixed in the airway. Data from our current work examining this process suggests that, although cells fixed in the airway such as fibroblasts and macrophages are activated in asthma and COPD and may activate T-cells, they do not seem to be causing T-cell proliferation. We now wish to extend these studies by determinimg if memory T- lymphocytes are proliferating in the airway wall within aggregations of lymphoid cells which act like lymph nodes and promote T-cell growth. To do this we will compare the number of these aggregations and the types of T-cells they contain in mild and severe cases of asthma and COPD with those in normal subjects. This work will provide new knowledge to help understand the mechanisms for the persistance of airway inflammation in asthma and COPD and may thereby also provide a focus for effective treatments of these condition.Read moreRead less