Functional Genomic Analysis Of Multidrug Efflux In The Emerging Pathogen Acinetobacter Baumannii
Funder
National Health and Medical Research Council
Funding Amount
$550,226.00
Summary
Infections due to antimicrobial resistant organisms are a major public health issue. Acinetobacter baumannii is a bacterium that is increasingly being identified as a significant cause of serious antibiotic resistant infections, especially in the intensive care unit setting. Molecular studies in Acinetobacter to identify and characterise drug resistance proteins that pump antibiotics out of the cell will help understand the resistance capabilities and potential of this bacterium.
Neurocognitive Studies Of Brain Plasticity Associated With Surgical Treatment Of Arteriovenous Malformations
Funder
National Health and Medical Research Council
Funding Amount
$701,922.00
Summary
We will use state-of-the-art brain imaging methods to test whether specific brain areas which have been chronically starved of adequate blood supply can regenerate, informing debate about limits on brain plasticity. Arteriovenous malformations (AVMs) are longstanding defects which can cause thinking skills to 'migrate' to other brain regions in childhood without noticeable impact. Surgical correction allows a test of what happens to the previously inactive area: Does the area 'start to think'?
Gastrointestinal Sensory Function In Normal And Diseased States
Funder
National Health and Medical Research Council
Funding Amount
$691,026.00
Summary
Chronic pain and discomfort from the digestive system is a major health care issue world-wide. There is currently no effective treatment for these problems, which often have no apparent organic cause. Lack of treatment is due to a lack of understanding about how sensations are transmitted from the digestive system to the brain. Our research group has unique and powerful techniques that allow us to probe the basic mechanisms of sensory function, and make rapid progress towards finding drugs that ....Chronic pain and discomfort from the digestive system is a major health care issue world-wide. There is currently no effective treatment for these problems, which often have no apparent organic cause. Lack of treatment is due to a lack of understanding about how sensations are transmitted from the digestive system to the brain. Our research group has unique and powerful techniques that allow us to probe the basic mechanisms of sensory function, and make rapid progress towards finding drugs that reduce specific types of sensory signals from the gut. We shall investigate sensory mechanisms in the upper and lower regions of the gut, where symptoms are most prevalent in diseases such as non-cardiac chest pain, functional dyspepsia and irritable bowel syndrome. Six aspects of sensory nerve endings in the gut are to be investigated: 1. The grouping of endings into functional classes (similar to touch or pressure receptors in skin) 2. How endings respond to chemicals and hormones found in the gut 3. How currently available drugs may be useful in reducing sensitivity 4. The mechanisms by which inflammation affects sensitivity 5. How nerve growth factors may trigger changes in sensitivity 6. How pores or channels in nerve endings determine their functionRead moreRead less
Identification Of Telomere-specific Recombination Pathways
Funder
National Health and Medical Research Council
Funding Amount
$540,075.00
Summary
Human cells stop to grow when the natural ends of chromosomes become too short. One way of how cancer cells evade this growth arrest is by using a copy-mechanism to extend short chromosome ends. Ironically, this copy mechanism is usually used by cells to keep the structure of chromosomes intact in order to prevent mutations that cause cancer. Here we will study a novel protein that contributes to the copy mechanism at short chromosome ends, but not as much in normal mutation prevention.
Functional Evaluation Of BRCA1 & BRCA2 Unclassified Sequence Variants And Identification Of Critical Pathogenic Domains.
Funder
National Health and Medical Research Council
Funding Amount
$331,312.00
Summary
The major genes that predispose to hereditary breast cancer are called BRCA1 and BRCA2. Most mutations in these genes cause the protein product to be truncated and inactive. However there are many families in which such truncating mutations are not found, but instead there are sequence changes that slightly alter the protein product. It is often difficult to predict whether these sequence variants are likely to cause hereditary breast cancer simply by looking at the position and nature of the se ....The major genes that predispose to hereditary breast cancer are called BRCA1 and BRCA2. Most mutations in these genes cause the protein product to be truncated and inactive. However there are many families in which such truncating mutations are not found, but instead there are sequence changes that slightly alter the protein product. It is often difficult to predict whether these sequence variants are likely to cause hereditary breast cancer simply by looking at the position and nature of the sequence change. Consequently, it is not possible to offer informative genetic counselling to these women or their at-risk family members. Assessment of the potential pathogenicity and functional significance of these unclassified sequence variants will be directly useful with regard to the clinical management of these women and their families, and will develop our current understanding of how different domains of these genes contribute to their role as cancer susceptibility genes.Read moreRead less
What Drives Abnormal Cerebral Activity In Secondary Generalised Epilepsy
Funder
National Health and Medical Research Council
Funding Amount
$565,809.00
Summary
Secondary Generalised epilepsy (2GE) is a severe, disabling epilepsy syndrome characterised by childhood onset frequent, treatment resistant seizures and developmental delay. Although one of the four major categories of epilepsy, it is poorly understood. This project uses combined EEG (brainwave testing) and MRI to reveal which brain areas are involved in the epileptic activity of 2GE. Advanced analysis techniques will explore which brain regions initiate 2GE epileptic activity.
A Genome-wide Linkage Study Of Schizophrenia In A Large Sample From Tamil Nadu, India
Funder
National Health and Medical Research Council
Funding Amount
$500,000.00
Summary
A Study of Schizophrenia in Tamil Nadu, India. The cause of schizophrenia is unknown, but there is good evidence that genes play a role. Geneticists do not fully understand how the disease is inherited, but it is very complex, and several interacting genes as well as environmental factors are probably involved. We have been recruiting families with at least two siblings with schizophrenia from a number of communities-casts in Tamil Nadu. We plan to recruit a total of 400 affected sibling familie ....A Study of Schizophrenia in Tamil Nadu, India. The cause of schizophrenia is unknown, but there is good evidence that genes play a role. Geneticists do not fully understand how the disease is inherited, but it is very complex, and several interacting genes as well as environmental factors are probably involved. We have been recruiting families with at least two siblings with schizophrenia from a number of communities-casts in Tamil Nadu. We plan to recruit a total of 400 affected sibling families, together with 400 trio families (both parents, plus their affected child). A genome-wide scan of the genetic code in all individuals will be conducted to identify chromosomal regions linked to schizophrenia. This is the first necessary step toward identifying schizophrenia susceptibility genes. If one or more genes are discovered, this will greatly improve our understanding of this disease. It will also stimulate the search for similar genes in other samples world-wide, including Australia where schizophrenia costs $2.5 billion annually in terms of treatment and loss of employment. With such a discovery, it may be possible to find better treatments that correct the basic cause of the illness and identify factors that protect against the illness.Read moreRead less
Brain Adaptation Associated With Spontaneous And Training-induced Recovery Of Touch Sensation Post-stroke.
Funder
National Health and Medical Research Council
Funding Amount
$339,950.00
Summary
Brain networks may reorganize to optimise stroke recovery. However, little is known about brain mechanisms underlying natural and training-induced recovery after stroke, particularly following loss of body sensations. Knowledge of the experiences that may facilitate brain reorganisation is a prerequisite for the development and evaluation of optimal stroke rehabilitation strategies. We aim to provide novel information on the potential benefits of specific training in facilitating reorganisation ....Brain networks may reorganize to optimise stroke recovery. However, little is known about brain mechanisms underlying natural and training-induced recovery after stroke, particularly following loss of body sensations. Knowledge of the experiences that may facilitate brain reorganisation is a prerequisite for the development and evaluation of optimal stroke rehabilitation strategies. We aim to provide novel information on the potential benefits of specific training in facilitating reorganisation of the brain after stroke. Specifically we will: (i) locate areas of brain activity associated with natural and training-induced recovery of touch sensation following stroke and (ii) investigate the relationship between brain activation, sensory recovery and intervening experience. Site and extent of brain activation associated with recovery of touch sensation will be investigated over time using serial functional magnetic resonance imaging (fMRI), a controlled sensory task and clinical measures of recovery. Thirty stroke patients with impaired touch sensation of the upper limb will be studied at 2-6 weeks and 6 months post-stroke to investigate changes in brain activation associated with natural recovery (Study 1). Ten healthy controls will also be studied over 6 months. Those patients who still have sensory loss at 6 months will then receive specific sensory training or placebo intervention to study the effect of training-induced recovery on brain activity (Study 2). The whole brain will be studied and activation sites will be interpreted relative to individual and standard brain maps. We expect that the findings will advance our knowledge of the relationship between clinical recovery, training and neural plastic changes in the brain. This information will provide direction for the development of scientifically based treatments designed to maximise recovery and help identify patients who are likely to show natural recovery and-or benefit from training.Read moreRead less