Validating And Optimising The Analysis Of Magnetic Resonance Physiology Data
Funder
National Health and Medical Research Council
Funding Amount
$91,725.00
Summary
Combined electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) is used to detect the anatomical areas in the brain that show electrical activity. Several centres worldwide use this technique to localise the seizure focus in patients with epilepsy. However, there is a lack of validation of the currently applied techniques. Current analysis methods have been developed and validated for other fMRI paradigms, such as motor tasks. It is not known whether the same principles ar ....Combined electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) is used to detect the anatomical areas in the brain that show electrical activity. Several centres worldwide use this technique to localise the seizure focus in patients with epilepsy. However, there is a lack of validation of the currently applied techniques. Current analysis methods have been developed and validated for other fMRI paradigms, such as motor tasks. It is not known whether the same principles are applicable and optimal for fMRI-EEG data. The proposed project aims at validating and optimising the analysis strategies for fMRI-EEG data.Read moreRead less
The 3-dimensional Structure Of Anticancer Drug-DNA Complexes Determined By X-ray Crystallography
Funder
National Health and Medical Research Council
Funding Amount
$264,358.00
Summary
Our main objective is to discover the molecular details of how cancer drugs interact with DNA and how these interactions differ from those of inactive chemically related compounds. We propose to use X-ray crystallography together with the successful methods we have developed for determining the 3-dimensional structures of the DNA complexes of a class of antitumour active drugs to study the complexes of other clinically or scientifically important DNA intercalating anticancer drugs. These agents ....Our main objective is to discover the molecular details of how cancer drugs interact with DNA and how these interactions differ from those of inactive chemically related compounds. We propose to use X-ray crystallography together with the successful methods we have developed for determining the 3-dimensional structures of the DNA complexes of a class of antitumour active drugs to study the complexes of other clinically or scientifically important DNA intercalating anticancer drugs. These agents act by poisoning the DNA binding enzyme topoisomerase. Crystallographic analysis will give us unequivocal answers at the atomic level as to the exact way in which the drug binds to DNA and how this binding differs between antitumour active and inactive compounds. We believe that a knowledge of the DNA binding mode of a class of intercalating anticancer drugs at the atomic level is valuable in guiding drug design within that class.Read moreRead less
The Structural Basis For The Action Of Anticancer DNA-intercalating Topoisomerase Poisons
Funder
National Health and Medical Research Council
Funding Amount
$459,750.00
Summary
Cancer kills one in four people in the Western world and half of those afflicted will die from the disease. If the malignancy is detected early, surgery and radiotherapy will often effect a cure but if the disease is disseminated at presentation then treatment requires chemotherapy. Chemotherapy can be curative for some tumour types but it is generally only palliative for the overwhelming majority of solid cancers. Consequently, there is an urgent need to improve the efficacy of anticancer drugs ....Cancer kills one in four people in the Western world and half of those afflicted will die from the disease. If the malignancy is detected early, surgery and radiotherapy will often effect a cure but if the disease is disseminated at presentation then treatment requires chemotherapy. Chemotherapy can be curative for some tumour types but it is generally only palliative for the overwhelming majority of solid cancers. Consequently, there is an urgent need to improve the efficacy of anticancer drugs. Many of these drugs work by binding directly to DNA and poisoning the DNA-manipulating enzyme, topoisomerase. Our objective is to discover the molecular basis of how anticancer drugs act through their interaction with DNA and topoisomerase. We propose to use the successful X-ray crystallography methods we have developed for determining the 3-dimensional structures of the DNA complexes of a class of anti-tumour active drugs, to study the complexes of other clinically or scientifically important DNA intercalating anticancer drugs. Crystallographic analysis provides unequivocal data, at near atomic resolution, of the nature of the molecular interactions which provide specificity and selectivity in drug-DNA complexes. This information will be a valuable guide in the further development of this important class of topoisomerase poisons as anticancer drugs. We will initiate structural studies of ternary complexes between the topoisomerase enzyme, DNA and anticancer drugs. The solution of the X-ray crystal structures of these ternary complexes will allow the design of new antitumour topoisomerase poisons to be put on a completely rational basis.Read moreRead less
Discovery And Validation Of Alzheimer�s Disease Biomarkers In Human Plasma
Funder
National Health and Medical Research Council
Funding Amount
$365,126.00
Summary
With life expectancy increasing Alzheimer�s disease (AD) poses a rising medical and socioeconomic challenge, emphasising the need for the development of prevention and treatment strategies. Such strategies will be most effective if administered early in the disease process, making early diagnosis critical to their success. The identification of biomarkers in this project, which are altered during the development of AD, will lead to the development of such a means to diagnosis AD at an early stag ....With life expectancy increasing Alzheimer�s disease (AD) poses a rising medical and socioeconomic challenge, emphasising the need for the development of prevention and treatment strategies. Such strategies will be most effective if administered early in the disease process, making early diagnosis critical to their success. The identification of biomarkers in this project, which are altered during the development of AD, will lead to the development of such a means to diagnosis AD at an early stage, when interventions will have the most impact.Read moreRead less
Incidence And Risk Factors For Cancer After Liver And Cardiothoracic Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$301,220.00
Summary
We will examine the incidence of cancer in patients before and after heart, lung, and liver transplantation. We will also examine the risk factors for cancer in these populations, including viral infection, time since transplantation, and the cause of organ failure. We will do this by linking data held by world-class Australian transplantation registries and the national cancer registry. Comparisons with other immune-deficient populations will allow valuable insight into the causes of cancer.
Chronic Disease Outcomes And Enhanced Primary Care In Seniors: A Cross-Jurisdictional Linkage Project
Funder
National Health and Medical Research Council
Funding Amount
$1,077,766.00
Summary
This project will provide evidence on how best to use the efforts of Australian GPs to obtain better outcomes in patients aged 65+ years who suffer from chronic diseases such as diabetes, heart disease and high blood pressure, asthma and emphysema, seizures and stomach disorders. It will also examine the best way that GP visits can promote healthier ageing in all older seniors, aged 75+ years. For each disease and in older seniors, the study will be able to detect which of the following factors ....This project will provide evidence on how best to use the efforts of Australian GPs to obtain better outcomes in patients aged 65+ years who suffer from chronic diseases such as diabetes, heart disease and high blood pressure, asthma and emphysema, seizures and stomach disorders. It will also examine the best way that GP visits can promote healthier ageing in all older seniors, aged 75+ years. For each disease and in older seniors, the study will be able to detect which of the following factors are the most important for better patient health: (i) seeing a GP more times, (ii) seeing a GP at more even intervals, (iii) seeing the same GP, or (iv) seeing a GP with a lot of experience in chronic diseases. Separate investigations will be made in older people living in hostels and nursing homes, because their needs may be different. The study will also evaluate the benefits of a major change that occurred to Medicare in 1999, when GPs were paid to perform health assessments and to prepare health plans (with other health workers) for patients with chronic health problems. The results will enable this important initiative to be further improved. The study will use a unique and new Australian research facility, which has brought together health data on the entire population of WA from both the State and Commonwealth levels, including information on Medicare use, pharmaceuticals, hospital stays and deaths. The facility works in such a way as to preserve patient and GP privacy. A strong feature of this research will be the degree of involvement of a representative and voluntary group of older Australian patients who attend GP clinics, and the GPs themselves, in advising the researchers on what's important to consumers and GPs.Read moreRead less
Opioid Dependent Persons In Pharmacotherapy: Blood Borne Viruses And Cancer Risk
Funder
National Health and Medical Research Council
Funding Amount
$88,495.00
Summary
Opioid dependent persons in pharmacotherapy in NSW are at increased risk of death from cancer. We will examine the occurrence of infection with hepatitis and HIV among this high-risk population using data linkage. We will define the relationship between infection, the duration, frequency and type of pharmacotherapy, and cancer risk. The findings will guide effective strategies that will reduce cancer incidence and mortality among this group, and minimise the associated health care costs.