Beta-lactamase Mediated Antibiotic Resistance In Gram-negative Pathogens: How Does Genotype Relate To Phenotype?
Funder
National Health and Medical Research Council
Funding Amount
$397,869.00
Summary
Unfortunately, one of the consequences of antibiotic usage (and in particular over-use and mis-use) is the development of resistance; if a small proportion of bacteria survive treatment, they can grow and replace the previous population of sensitive bacteria. In addition, the genes that confer resistance can be transferred between different bacterial lineages, thus facilitating the dissemination of resistant bacteria. The most important mechanism of penicillin resistance is through the expressio ....Unfortunately, one of the consequences of antibiotic usage (and in particular over-use and mis-use) is the development of resistance; if a small proportion of bacteria survive treatment, they can grow and replace the previous population of sensitive bacteria. In addition, the genes that confer resistance can be transferred between different bacterial lineages, thus facilitating the dissemination of resistant bacteria. The most important mechanism of penicillin resistance is through the expression of an enzyme called a beta-lactamase. This enzyme breaks down the penicillin. Beta-lactamase enzymes come in many different varieties, and new varieties appear quite frequently. Remarkably, when new kinds of penicillin are invented to circumvent resistance, the appearance of new beta-lactamases that can break down these new penicillins follows shortly thereafter. The objectives of our research are twofold. Firstly, it is now clear that the relationship between the beta-lactamase genes in a bacterium and the resulting pattern of resistance can be very complex. It can involve both the broad nature of the genes, the numbers of duplicates of the genes inside the cell, and very minor changes to the gene sequences. We will probe the relationship between the gene and resistance so as to understand it at a deeper level. Secondly, we will use this information to develop very efficient and cost affective methods for keeping track of the spread of the different varieties of beta-lactamase genes. These methods will be designed to be carried out on real-time PCR machines. These high-tech devices are general purpose gene analyzers that can carry out many different kinds of genetic assay. They are rapidly becoming ubiquitous in clinical microbiology laboratories. The use of these methods will provide much hard information that will be used to minimise the dissemination of antibiotic resistance.Read moreRead less
Functional MRI And MR Spectroscopic Studies Of Penicillin Induced And Kindled Sheep Models Of Epilepsy
Funder
National Health and Medical Research Council
Funding Amount
$311,244.00
Summary
Epilepsy is one of the most common neurological disorders, affecting 1-2% of the population. Many epilepsy patients do not respond to drug therapy and their only hope for seizure control is surgical removal of the part of the brain responsible for their seizures. Successful surgery is very much dependent on the ability to exactly localize the seizure focus and this is often not possible using the imaging techniques currently available. Functional magnetic resonance imaging (fMRI) is a new techni ....Epilepsy is one of the most common neurological disorders, affecting 1-2% of the population. Many epilepsy patients do not respond to drug therapy and their only hope for seizure control is surgical removal of the part of the brain responsible for their seizures. Successful surgery is very much dependent on the ability to exactly localize the seizure focus and this is often not possible using the imaging techniques currently available. Functional magnetic resonance imaging (fMRI) is a new technique which may improve our ability to localize the seizure focus from which seizures arise, if the brain can be imaged at, or near, the time of a seizure. MR spectroscopy (MRS) enables us to detect metabolic changes in the brain which may persist at the site where seizures have begun for up to 30 minutes after the seizure. The aim of our research is to obtain a greater understanding of the changes detected with these MR modalities so that we can learn to apply these techniques to human sufferers of epilepsy. Ultimately it may help enable previously incurable epilepsy patients to undergo successful surgery and live normal lives.Read moreRead less
Radiotherapy Treatment For Prostate Cancer - A Change In Practice Based On Direct Evidence For Targeting And Toxicity Effects Using Real Outcomes Data
Funder
National Health and Medical Research Council
Funding Amount
$555,129.00
Summary
Radiotherapy for prostate cancer treatment will be more effective when we have better knowledge of what patient anatomy needs to be targeted, and what needs to be avoided. This project will combine data collected during a large Australasian prostate cancer radiotherapy trial, ‘RADAR’, with data collected using new patient imaging methods to determine how patient anatomy impacts on the effectiveness of their treatment and the side-effects they experience.
Developing New Treatment Approaches For Severe And Treatment Resistant Depression
Funder
National Health and Medical Research Council
Funding Amount
$2,060,520.00
Summary
Depression is a common, disabling problem. One third of depressed patients do not respond to treatment with standard medications and psychological therapy. This research program will focus on developing new treatment approaches for these people: optimising electroconvulsive therapy, a highly effective treatment, developing new non invasive brain stimulation treatments, generating new knowledge on how best to use ketamine treatment.
Electrical Stimulation With A “Random Noise” Pattern: A New Approach For The Treatment Of Depression
Funder
National Health and Medical Research Council
Funding Amount
$523,160.00
Summary
This study is a world first, examining the use of a novel technology to treat depression by stimulating the brain mildly and non invasively. The study will examine the effectiveness of a 4-week course of Transcranial “Random Noise” Stimulation to treat depression, and will also measure whether improvement in mood is accompanied by a restoration of brain plasticity or adaptability.
Novel Inhalation Formulation Of Bacteriophages Against ‘superbugs’ Causing Respiratory Infections
Funder
National Health and Medical Research Council
Funding Amount
$563,621.00
Summary
Emergence of superbugs has led to life-threatening respiratory infections that are resistant to most antibiotics. There is an urgent need for alternative treatments not relying on antibiotics. Bacteriophages (or ‘bacteria eaters’) are natural predators of bacteria and are unaffected by antibiotic resistance. This multi-disciplinary project will develop novel therapeutics using inhaled bacteriophages against bacterial infections in the lungs.
The Impact Of The Neonatal Gut Microbiome On Specific And Nonspecific Vaccine Responses.
Funder
National Health and Medical Research Council
Funding Amount
$661,496.00
Summary
Humans are colonised by a large and diverse group of microorganisms, collectively known as the microbiome. The gut microbiome, in particular, hosts an enormous abundance and diversity of bacteria, which perform a range of essential beneficial functions. Our study will investigate whether disruption of the gut microbiome in newborns, for example through antibiotic usage or maternal diet, leads to an impairment of subsequent immune responses to childhood immunisations.
Exploring The Pluridimensionality Of Drug Efficacy.
Funder
National Health and Medical Research Council
Funding Amount
$326,184.00
Summary
Dysfunction of cell surface receptors is the underlying cause of many pathological conditions. Using cell based screening methods we aim to investigate the mechanisms underlying drug action, to understand how drugs acting at common targets promote distinct biological responses. This will aid the development of new therapeutics based on the ability to predict specific drug effects.
A New, Low-cost E-health Treatment For Alcohol Use Disorder Using Mental Imagery
Funder
National Health and Medical Research Council
Funding Amount
$895,032.00
Summary
This project offers the first large-scale test of phone-based Functional Imagery Training (FIT), a new, low-cost way to help people change behaviours using mental imagery, regardless of where they live. The trial addresses Alcohol Use Disorder—a common problem with substantial health and social impacts, comparing FIT with verbal motivational treatments, and testing effects on alcohol use and quality of life over 12 months. Cost-effectiveness and predictions of outcome are also examined.