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
Sensitive Serum Markers For Improved Diagnosis, Monitoring And Screening For Early Detection Of Mesothelioma
Funder
National Health and Medical Research Council
Funding Amount
$410,880.00
Summary
The deadly asbestos-induced cancer mesothelioma is continuing to kill tens of thousands of individuals per year and its incidence is increasing. Mesothelioma is predicted to cost communities hundreds of billions of dollars in compensation. This disease is unusually difficult to diagnose and tends to be already quite advanced by the time patients present to the doctor with symptoms. Unfortunately, treatment options for the majority of patients are limited and most die within a year of diagnosis. ....The deadly asbestos-induced cancer mesothelioma is continuing to kill tens of thousands of individuals per year and its incidence is increasing. Mesothelioma is predicted to cost communities hundreds of billions of dollars in compensation. This disease is unusually difficult to diagnose and tends to be already quite advanced by the time patients present to the doctor with symptoms. Unfortunately, treatment options for the majority of patients are limited and most die within a year of diagnosis. In different forms of cancer, levels of certain proteins in the blood can be measured and have been shown to indicate the presence of tumour and in some cases the extent of tumour. These proteins are collectively known as tumour markers. Tumour markers for ovarian, prostate, breast and other cancers are used by doctors to help with the diagnosis of specific cancers, to monitor the patients response to treatment and to give a valuable early warning of remission or relapse. There is no tumour marker currently used for patients with mesothelioma. We have shown in early studies published in the prestigious journal The Lancet that soluble mesothelin related protein (SMRP) is actually elevated in more than 75% of mesothelioma patients and in less than 2% of patients with other cancer and non-cancer lung diseases. In this current project we plan to extend our studies looking at blood levels of SMRP to see if they will help in the care of patients with mesothelioma. So far we have done most of the work in a particular group of patients, but it is vital that the work be extended to other groups with different types and durations of exposure to asbestos and to different areas of the country. As part of that we need to test how stable the molecule is in blood samples, because if it is not very stable it wont be a very pratical test. We also plan to look at some other markers that have been clinically useful in other forms of cancer and we will try to identify new, novel mesothelioma specific markers. This work has the potential to impact on patient care in many centres of the world.Read moreRead less
Development Of National Protocols For The Detection Of Influenza A H5N1
Funder
National Health and Medical Research Council
Funding Amount
$248,229.00
Summary
This project will develop a best practice approach to the diagnosis of influenza A H5N1 (Bird Flu) in Australian public health laboratories. Tests such as reverse transcription polymerase chain reaction (RT-PCR) are in use globally for influenza A H5N1 detection. Some proprietary rapid influenza A tests also claim to detect influenza A H5N1. However there is little information on systematic evaluation of these, largely because there have been relatively few human influenza A H5N1 cases and patie ....This project will develop a best practice approach to the diagnosis of influenza A H5N1 (Bird Flu) in Australian public health laboratories. Tests such as reverse transcription polymerase chain reaction (RT-PCR) are in use globally for influenza A H5N1 detection. Some proprietary rapid influenza A tests also claim to detect influenza A H5N1. However there is little information on systematic evaluation of these, largely because there have been relatively few human influenza A H5N1 cases and patient specimens. Australian laboratories need authoritative guidelines as to optimal influenza tests, target genes and reagents. Development of a simple, potentially automated type specific test for influenza A H5N1 antibody such as enzyme immunoassay (EIA) is also desirable, as widely used tests cannot distinguish between infection with H5 or other influenza types. Reference methods such as haemagglutination inhibition (HAI) are cumbersome. In this project mock specimens for virus and antibody detection will be created using viral cell culture and infected chicken derived influenza A H5N1. This will be undertaken in physical containment level 4 (PC4) facilities in Australia's designated human and animal PC4 laboratories. This material will be used for (i) specimen panels to compare the performance of candidate laboratory tests (ii) positive control material in all tests undertaken and (iii) quality assurance exercises to ensure high standards of testing. Using these panels the group will assess influenza H5N1 RT-PCR, tests for detection of influenza proteins including immunofluorescence, and rapid point of care influenza A detection tests available in Australia. An EIA method currently used to detect influenza antibodies from different animal species will be refined to develop a simple test for type specific detection influenza A H5N1 antibodies, and subsequently evaluated using animal sera. A standard method for HAI reference serology for use in public health laboratories will also be recommended, and the best approaches to high throughput automated RT-PCR, and performing RT-PCR in the field on portable instrumentation will be explored. Recommendations for standard protocols for influenza A H5N1 will be developed and will submitted for review and endorsement by Commonwealth ministerial advisory committees.Read moreRead less
Gene Based Treatment Strategies For Diabetic Retinopathy
Funder
National Health and Medical Research Council
Funding Amount
$2,630,000.00
Summary
Diabetic retinopathy is the leading cause of blindness in the working population of developed countries and it is an increasing problem in the developing world. Present therapy involves extensive laser destruction of the light-detecting part of he retina. In addition, it is not only effective when administered at an appropriate stage in the disease process. Consequently, there is an urgent need for the development of better, prophylactic, easily administrable and cheaper therapies. This project ....Diabetic retinopathy is the leading cause of blindness in the working population of developed countries and it is an increasing problem in the developing world. Present therapy involves extensive laser destruction of the light-detecting part of he retina. In addition, it is not only effective when administered at an appropriate stage in the disease process. Consequently, there is an urgent need for the development of better, prophylactic, easily administrable and cheaper therapies. This project aims to develop a potentially permanent solution to alleviate diabetes-related blindness in the world. The project combines several very recent scientific advances into one strategy to combat diabetic retinopathy at a molecular level. Vision is our most important sensory organ that cannot be replaced. Thus, human trials can only be conducted following extensive animal safety and efficacy trials. To date the development of new therapies has been seriously hampered by the lack of appropriate, easy to reproduce animal models for different stages of diabetic retinopathy. In addition, it aims to identify new therapeutic agents from molecules that are naturally produced by the retina while fighting the disease. Finally, tested and evaluated in the animal models. The most successful therapeutic candidates will then be further developed for human trials.If successful, our approach will potentially have a major impact on the treatment of diabetic retinopathy and possibly on all diabetic vascular diseases. A single injection might only be necessary to prevent the development of diabetic retinopathy, which would represent a significant weapon in the management of patients. In addition, successful application of secretion gene therapy in the eye might open up the possibility to introduce the same concept for the treatment of larger organs undergoing microvascular changes as a result of diabetes.Read moreRead less
A Computer Model Of Service Delivery For Behavioural And Psychological Symptoms Of Dementia: A Tool For Policy Makers An
Funder
National Health and Medical Research Council
Funding Amount
$400,108.00
Summary
Behavioural and psychological symptoms of dementia (BPSD) affect approximate 90% of persons with dementia. BPSD include depression, aggression and psychosis and have negative effects on persons with dementia and carers. Management of BPSD is costly. This project will update and enhance our theoretical model of service delivery for BPSD by turning it into a computer-based model to assist health managers and policy makers. This model will incorporate the projected increase in prevalence of dementi ....Behavioural and psychological symptoms of dementia (BPSD) affect approximate 90% of persons with dementia. BPSD include depression, aggression and psychosis and have negative effects on persons with dementia and carers. Management of BPSD is costly. This project will update and enhance our theoretical model of service delivery for BPSD by turning it into a computer-based model to assist health managers and policy makers. This model will incorporate the projected increase in prevalence of dementia and project associated costs of care into the future. It will also incorporate information about interventions for BPSD, and how they may affect prevalence and cost in the future.Read moreRead less