Molecular Characterisation Of Early Precursor Lesions Of A Novel Ñserrated Pathwayî Of Colorectal Cancer Using Gene Expression And Proteomics.
Funder
National Health and Medical Research Council
Funding Amount
$318,338.00
Summary
In Australia, CRC is the second highest cause of all cancer-related deaths. If detected early, CRC has a high success rate of cure, but a percentage of precursor lesions escape detection and show aggressive clinical behaviour to progress to CRC. These are difficult to diagnosis with existing technologies. We aim to understand the biology behind sessile serrated adenoma pathways and hence enhance early detection, diagnosis and treatments strategies.
One of the current challenges in public health is to translate the progress from the Human Genome Project into reduced morbidity and mortality from disease. Once genetic defects are characterised, knowledge about the variability in severity of disease in mutation carriers, is important from a public health perspective. Hereditary Haemochromatosis (HH) is a common genetic disorder of iron overload that results in a wide spectrum of disease, varying from non-specific symptoms to severe damage to l ....One of the current challenges in public health is to translate the progress from the Human Genome Project into reduced morbidity and mortality from disease. Once genetic defects are characterised, knowledge about the variability in severity of disease in mutation carriers, is important from a public health perspective. Hereditary Haemochromatosis (HH) is a common genetic disorder of iron overload that results in a wide spectrum of disease, varying from non-specific symptoms to severe damage to liver, heart, pancreas and joints from iron deposition. It is easily treatable by regular blood donation, and population-based screening for HH has therefore been advocated. In this study we aim to address gaps in the existing data on HH regarding dietary and lifestyle factors that contribute to the variable clinical picture of HH. The study will be based on the Melbourne Collaborative Cohort Study, a cohort of 31,500 men and women who have been followed for approximately 10 years. Information on dietary and lifestyle factors was collected at initial enrollment, along with a blood specimen. We will test all non-Southern European participants (31,176) for the common HH mutations in the HFE gene and then select a subgroup of 1150 people, including all people with the main genetic defect as well as a comparison group, for further clinical followup. Participants will have genetic counselling and informed consent will be obtained. Participants will complete a short questionnaire and give a blood sample for measurement of iron overload, liver function, and other relevant blood tests, then undergo a brief clinical examination. Results of all tests will be given at a followup visit by genetic counsellor or physician. This study will provide important data on natural history of HH risk factors that influence variability in clinical presentation and the association of HFE mutations with chronic diseases and all cause mortality.Read moreRead less
Establishment Of A Latrobe Valley Power Industry Cohort And Biospecimen Bank For The Study Of Asbestos Related Disease
Funder
National Health and Medical Research Council
Funding Amount
$614,466.00
Summary
The Latrobe Valley has been the site of Victoria�s electricity generation since the 1920�s. Very large amounts of asbestos were used in the construction of power stations and housing for the workers employed to build and operate them. Asbestos is known to cause a tumour of the lining of the lung cavity called mesothelioma. Mesothelioma is a highly debilitating tumour, with a median survival as low as seven months following diagnosis. Mesothelioma can occur in asbestos exposed individuals up to f ....The Latrobe Valley has been the site of Victoria�s electricity generation since the 1920�s. Very large amounts of asbestos were used in the construction of power stations and housing for the workers employed to build and operate them. Asbestos is known to cause a tumour of the lining of the lung cavity called mesothelioma. Mesothelioma is a highly debilitating tumour, with a median survival as low as seven months following diagnosis. Mesothelioma can occur in asbestos exposed individuals up to forty years following exposure, and as such, the peak number of cases of mesothelioma is not expected in Australia for another 10-20 years. The incidence of mesothelioma in the Latrobe Valley is several fold the state average. We will recruit a cohort of 5000 asbestos exposed former power industry workers, and provide information, support and smoking cessation campaigns. For 1000 of the most highly exposed we will offer annual testing for mesothelin, a protein in the blood which may indicate the presence of mesothelioma prior to a clinical diagnosis.Read moreRead less
Neisseria Gonorrhoeae Antmicrobial Resistance: Detection And Propagation
Funder
National Health and Medical Research Council
Funding Amount
$435,129.00
Summary
Neisseria gonorrhoeae, the pathogen that causes gonorrhoea, has developed resistance to multiple classes of antibiotics. The last remaining class of antibiotics that can successfully be used for general treatment of gonorrhoea is extended spectrum cephalosporins (ESCs). However, we are now starting to see Neisseria gonorrhoeae isolates with early signs of ESC resistance. This research will use molecular technology and mathematical modelling to investigate Neisseria gonorrhoeae antimicrobial resi ....Neisseria gonorrhoeae, the pathogen that causes gonorrhoea, has developed resistance to multiple classes of antibiotics. The last remaining class of antibiotics that can successfully be used for general treatment of gonorrhoea is extended spectrum cephalosporins (ESCs). However, we are now starting to see Neisseria gonorrhoeae isolates with early signs of ESC resistance. This research will use molecular technology and mathematical modelling to investigate Neisseria gonorrhoeae antimicrobial resistance in Australia.Read moreRead less
Genomic Approaches To Understand And Control The Emergence Of Vancomycin Resistant Enterococcus Faecium (VREfm) In Australia.
Funder
National Health and Medical Research Council
Funding Amount
$756,163.00
Summary
VRE is a serious hospital superbug that has been increasing in many major hospitals around Australia, while at the same time MRSA (Golden Staph) infections have been decreasing. This project will find out why VRE is increasing by examining what happens to patients at a major Australian hospital from their time of admission to the onset of infection with VRE. At the end of the project we will have the first real understanding of how VRE is transmitted so we can develop effective infection control ....VRE is a serious hospital superbug that has been increasing in many major hospitals around Australia, while at the same time MRSA (Golden Staph) infections have been decreasing. This project will find out why VRE is increasing by examining what happens to patients at a major Australian hospital from their time of admission to the onset of infection with VRE. At the end of the project we will have the first real understanding of how VRE is transmitted so we can develop effective infection control measures.Read moreRead less
Molecular Markers Of Phenotype, Therapeutic Responsiveness And Prognosis In Human Cancers.
Funder
National Health and Medical Research Council
Funding Amount
$11,762,117.00
Summary
This proposal aims to identify molecular markers that can be used to classify subtypes of particular cancers according to their prognosis and response to therapy. This will optimise selection of patients for the most appropriate treatment and lead to the development of new therapeutic strategies.
TB is a global public health problem, responsible for the deaths of 2 million children and young adults annually. Drug resistant strains of TB are emerging and pose a threat even in countries where TB is well controlled, such as Australia. Research undertaken in this CRE will translate into improved treatments, diagnostics and strategies to prevent transmission. The CRE will build capacity for research on TB in our region and provide a legal framework to support public health policy.
Can Skin Infection With Group A Streptococcus Cause Acute Rheumatic Fever?
Funder
National Health and Medical Research Council
Funding Amount
$459,450.00
Summary
It is traditionally taught that the cause of acute rheumatic fever (ARF) is always infection of the throat with the bacterium group A streptococcus (GAS). However, in Aboriginal communities of the Top End of the Northern Territory the incidence of ARF is the highest reported in the world, yet GAS is uncommonly isolated from the throat. There is further information to suggest that GAS skin sores may underlie many cases of ARF. If this were proven, it would completely alter the traditional view of ....It is traditionally taught that the cause of acute rheumatic fever (ARF) is always infection of the throat with the bacterium group A streptococcus (GAS). However, in Aboriginal communities of the Top End of the Northern Territory the incidence of ARF is the highest reported in the world, yet GAS is uncommonly isolated from the throat. There is further information to suggest that GAS skin sores may underlie many cases of ARF. If this were proven, it would completely alter the traditional view of the cause of ARF, and have important implications for prevention of ARF around the world. Presently, these approaches focus on diagnosing and treating sore throat, but no country has proven that such a program can be successful in substantially reducing new cases of ARF. If it was known that skin infection could lead to ARF, then countries (including Australia) could emphasise the importance of skin health programs. A further benefit of this knowledge would be to influence GAS vaccine development, which presently is largely focused on the prevention of sore throat. A different possibility has recently been raised - that the cause of ARF may not always be GAS, but instead that the related bacteria GCS and GGS may have the potential to cause this disease. Proof of this hypothesis would even more dramatically alter our understanding of disease causation, prevention, and vaccine development. We propose to determine the cause of ARF in Aboriginal communities by regularly swabbing families of people with a history of ARF, and using genetic fingerprinting of the bacteria from the skin and throat swabs. When cases of ARF occur, we will be able to determine the site and type of infection that precipitated the attack. We will conduct a related study in more communities, in which we will swab family members of people with ARF and of control families (without ARF) to determine the bacteria most commonly isolated from ARF families.Read moreRead less
A Study Of The Molecular Epidemiology And Virulence Determinants Of Enterovirus 71 Strains From The Asia-Pacific Region
Funder
National Health and Medical Research Council
Funding Amount
$286,325.00
Summary
In this study, we aim to understand the reasons for the emergence of epidemics of severe neurological disease due to enterovirus 71 (EV71) in young children of the Asia-Pacific region since 1997, and to develop strategies for disease prevention. EV71 is a human enterovirus closely related to the polioviruses. Most infections with EV71 are trivial, however, they may occasionally result in severe disease, including brainstem encephalitis with a high mortality and acute flaccid paralysis similar to ....In this study, we aim to understand the reasons for the emergence of epidemics of severe neurological disease due to enterovirus 71 (EV71) in young children of the Asia-Pacific region since 1997, and to develop strategies for disease prevention. EV71 is a human enterovirus closely related to the polioviruses. Most infections with EV71 are trivial, however, they may occasionally result in severe disease, including brainstem encephalitis with a high mortality and acute flaccid paralysis similar to poliomyelitis. There has been a large increase in EV71 epidemic activity throughout the Asia-Pacific region since 1997, including a large epidemic in Perth, Western Australia in 1999. These epidemics have resulted in many deaths and cases of severe neurological disability. In view of the severity of EV71 neurological disease and the lack of effective treatments, our research effort needs to focus on prevention through public health surveillance and vaccine development. The major aims of our study are two-fold: 1. To study the origin and evolution of EV71 in the Asia-Pacific region using molecular techniques and to use this information to implement surveillance in Australia and Southeast Asia. It is anticipated that improved surveillance will provide early warning of impending epidemics. 2. To understand the molecular basis of virulence of EV71, with emphasis on the ability of virus to cause severe disease of the central nervous system. This study will have two goals: a. To identify the human cellular receptor of EV71. The ultimate goal of this research will be the development of a small animal model of EV71 encephalitis by constructing a transgenic mouse expressing the human cellular receptor for EV71. b. To construct an infectious cDNA clone of EV71 and to develop genetically defined attenuated strains by mutagenesis of the infectious clone. Mutant strains of EV71 will be tested for replication and virulence in newborn mice and in human neuroblastoma cells.Read moreRead less