The hERG potassium ion channel is critical for the maintenance of the normal rhythm of the heartbeat. The aim of this study is to map the temporal sequence of the movements of different parts of the hERG K+ channel that regulate the opening and closing of the extracellular gate of the channel. To achieve this, we will use the powerful protein engineering technique of phi-value analysis, a technique that has never before been applied to voltage-gated ion channels.
Using Evidence To Set Priorities In Health: An Analysis Of Decisions Of The Pharmaceutical Benefits Advisory Committee
Funder
National Health and Medical Research Council
Funding Amount
$174,575.00
Summary
Australia has pioneered the use of rigorous clinical and economic evidence in the evaluation of drugs prior to funding on our nationally subsidised Pharmaceutical Benefits Scheme. In the ten years since the introduction of the requirement that drugs demonstrate cost effectiveness prior to subsidy being granted there has been no formal independent evaluation of the system to assess its performance. This project will examine the recommendations of the Pharmaceutical Benefits Advisory Committee in ....Australia has pioneered the use of rigorous clinical and economic evidence in the evaluation of drugs prior to funding on our nationally subsidised Pharmaceutical Benefits Scheme. In the ten years since the introduction of the requirement that drugs demonstrate cost effectiveness prior to subsidy being granted there has been no formal independent evaluation of the system to assess its performance. This project will examine the recommendations of the Pharmaceutical Benefits Advisory Committee in the last decade and consider the factors that explain those decisions. At times it has been asserted that those decisions have been arbitrary or based on inappropriate considerations such as the financial cost to government or politics of the day rather than the value for money of the drug in question. We will examine the reasons behind the decisions against the objectives of providing access to life enhancing medicines in a cost effective manner. We will look at what are the key determinants of whether a drug is recommended for listing on the PBS or is rejected. A key focus will be on whether those determinants could be described as legitimate in terms of their consistency with the objectives of the scheme. For example whether the main cause of rejection is a lack of high quality evidence on effectiveness- cost effectiveness or simply because of factors such as the high financial cost to government. The project will create a database of all submissions to the PBAC 1992-2004 that will allow us to explore a number of questions about the effectiveness of the decision making process in using evidence on effectiveness and costs in health more broadly as well as those specific to the PBS. In highlighting some of the problems with the evidence and its interpretation the overall aim is to improve the quality of the decision making process in the future.Read moreRead less
Use Of Expression Profiling To Identify Genes Influencing Cardiovascular Risk In The Norfolk Island Population Isolate
Funder
National Health and Medical Research Council
Funding Amount
$697,409.00
Summary
This study will use a unique population isolate from Norfolk Island. We aim to identify genes that play a role in cardiovascular disease risk. Norfolk has a population of ~1200 permanent residents, most of whom are direct descendents of 18th century English Bounty mutineers and Polynesian women. We will undertake gene expression mapping to identify genomic loci that influence cardiovascular disease using samples from this population isolate.
Fine Scale Mapping And Identification Of The IBD1 Gene On Chromsosome 16
Funder
National Health and Medical Research Council
Funding Amount
$483,849.00
Summary
One of the greatest challenges facing contemporary gastroenterology is to understand the causes of the inflammatory bowel diseases (IBD). Studies on the prevalence, incidence and cost of IBD indicate that these diseases have considerable impact in Australia. On average, patients lose more than 13 days from work each year, and in hospital, IBD in-patients accounted for 7% of total admissions and 10% of total bed days at an average cost of $2600 per admission. We estimate that there may be more th ....One of the greatest challenges facing contemporary gastroenterology is to understand the causes of the inflammatory bowel diseases (IBD). Studies on the prevalence, incidence and cost of IBD indicate that these diseases have considerable impact in Australia. On average, patients lose more than 13 days from work each year, and in hospital, IBD in-patients accounted for 7% of total admissions and 10% of total bed days at an average cost of $2600 per admission. We estimate that there may be more than 10,000 Australians who suffer from IBD. The existence of a genetic predisposition to IBD is now well established, and there is strong evidence that the disease is complex, resulting from the interaction of a number of different genes. To date, one genetic localisation on chromosome 16 has been established in several different populations, and we have confirmed the importance of this localisation in the Australian population. We will further refine the localisation by fine scale mapping in the pericentromeric region of chromosome 16 by identifying and studying the inheritance of novel markers in the region. We will then identify and characterise the gene itself using several complementary appoaches that rely on differences at the molecular level between disease and normal tissue. This work is part of the international effort to identify all IBD susceptibility genes. Once that is achieved, approaches to explaining the interactions between the genes, their protein products and environmental triggers can be determined. Only when the mechanisms of these interactions are understood will the expectation of rational therapies based on an understanding of disease aetiology be possible.Read moreRead less
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