Translating Bacterial Molecular Epidemiology Into Information To Improve Infectious Disease Risk Assessment And Control
Funder
National Health and Medical Research Council
Funding Amount
$494,500.00
Summary
Streptococcus pneumoniae (pneumococcus) and group B streptococcus (GBS) are important pathogenic bacteria, which cause septicaemia and meningitis in young infants, the elderly and people with certain chronic diseases. Both consist of a number of different types, some of which are more likely to cause disease than others. Pneumococcal vaccines that protect against the commonest pathogenic types are used in Australia in people most at risk.Antibiotic resistance is an increasing problem, which shou ....Streptococcus pneumoniae (pneumococcus) and group B streptococcus (GBS) are important pathogenic bacteria, which cause septicaemia and meningitis in young infants, the elderly and people with certain chronic diseases. Both consist of a number of different types, some of which are more likely to cause disease than others. Pneumococcal vaccines that protect against the commonest pathogenic types are used in Australia in people most at risk.Antibiotic resistance is an increasing problem, which should be partly off-set by immunisation. Giving antibiotics during labour, to women colonised with GBS, can reduce infection rates in newborns, but there are many disadvantages of this approach, including the risk of increased antibiotic resistance. Vaccines against GBS are mpt yet available. We have developed methods to identify detailed fingerprints of these bacteria which allow us to identify types, antibiotic resistance and, for GBS, other characteristics which can distinguish highly pathogenic strains from the majority that are carried harmlessly and unlikely to cause disease. The methods are still quite slow and expensive and produce complex patterns,which are difficult to interpret rapidly. We plan to develop a new, rapid and relatively inexpensive, fingerprinting system for these bacteria and computer programs to analyse and interpret the results. They will allow us to check the strains of pneumococci that cause disease to make sure that new ones, not covered by the vaccine, do not become more common and reduce the effectiveness of vaccine and that antibiotic resistance does not increase further. The methods will also allow us to study differences between the small proportion of GBS strains that cause neonatal infection and the majority that are carried harmlessly by pregnant women and are of little risk to their babies. Eventually this should allow doctors to identify women whose babies are most at risk, reduce unnecessary antibiotic use.Read moreRead less
The amygdala is an area of the brain that is involved in assigning emotional content to sensory information. Disorders of the amygdala lead to a variety of anxiety-related mental disorders such as panic attacks and post-traumatic stress. This grant will study how the NMDA receptor, which plays a central role in memory formation, works in the amygdala. We will determine the functional role of this receptor in the amygdala and how it may be modified by experience.
The Extinction Of Conditioned Fear And Its Implications For Cue Exposure Therapy
Funder
National Health and Medical Research Council
Funding Amount
$322,430.00
Summary
This project studies extinction of Pavlovian conditioned fear reactions in rats. Extinction of these reactions is an animal model for exposure therapy used in the treatment of anxiety disorders in people. In exposure therapy, the patient, aided by the clinician, confronts trauma-related cues in the absence of any overt danger. The intention of this therapy is to reduce the ability of the trauma-related cues to provoke the fear reactions that are undermining the patient's quality of life. In Pavl ....This project studies extinction of Pavlovian conditioned fear reactions in rats. Extinction of these reactions is an animal model for exposure therapy used in the treatment of anxiety disorders in people. In exposure therapy, the patient, aided by the clinician, confronts trauma-related cues in the absence of any overt danger. The intention of this therapy is to reduce the ability of the trauma-related cues to provoke the fear reactions that are undermining the patient's quality of life. In Pavlovian conditioning, subjects (typically rats) are exposed to a signaling relation between an initially neutral stimulus (e.g., a noise) and a feared outcome (e.g., foot shock). When later repeatedly exposed to the initially neutral but now feared stimulus (the noise) in the absence of the feared outcome, the fear reactions it acquired progressively decline until eventually it fails to elicit any such reactions. The fear reactions are said to have been extinguished. There has been significant progress in understanding the psychological processes and neural mechanisms underlying the acquisition of fear reactions, but much less is known about the processes and mechanisms underlying the extinction of these reactions. The project has two general objectives. The first is to determine the conditions of extinction training that promote long-term loss of fear reactions. The second objective is to determine how the brain controls this extinction of learned fear. Achieving these aims will be significant for two reasons. First, it will contribute to understanding the mechanisms by which animals (including people) learn to adjust their behaviour to bring it into line with the current relations that exist between events in the world. Second, it will provide important information about how such adjustment is facilitated or impaired across extinction training and, thereby, contribute towards understanding both the successes and failures of cue exposure therapy for fear-related disorders.Read moreRead less
Disorders of fear and anxiety impose significant burdens on individual sufferers, their families, and communities. This project studies the brain mechanisms of fear and anxiety, with special focus on the role of the prefrontal cortex. It tests the novel hypothesis that prefrontal cortex is part of a neural pathway critical for regulating fear learning and ensuring that fear learning is adaptively guided by past experience. In the absence of this pathway, fear learning is maladaptive and excessiv ....Disorders of fear and anxiety impose significant burdens on individual sufferers, their families, and communities. This project studies the brain mechanisms of fear and anxiety, with special focus on the role of the prefrontal cortex. It tests the novel hypothesis that prefrontal cortex is part of a neural pathway critical for regulating fear learning and ensuring that fear learning is adaptively guided by past experience. In the absence of this pathway, fear learning is maladaptive and excessive relative to the danger posed by a situation.Read moreRead less
Mechanisms And Consequences Of Cholinergic Signaling In Neocortical Pyramidal Neurons
Funder
National Health and Medical Research Council
Funding Amount
$258,000.00
Summary
Dementia, including Alzheimer s Disease, represents the second highest non-fatal disease burden in Australia. Modern theories suggest that cognitive deficits associated with disorders such as Alzheimer s Disease result in part from impairment of the action of the neurotransmitter acetylcholine. Despite the obvious importance of acetylcholine in brain function, there is currently a lack of basic knowledge regarding how this chemical works at the cellular level. We have recently discovered that ac ....Dementia, including Alzheimer s Disease, represents the second highest non-fatal disease burden in Australia. Modern theories suggest that cognitive deficits associated with disorders such as Alzheimer s Disease result in part from impairment of the action of the neurotransmitter acetylcholine. Despite the obvious importance of acetylcholine in brain function, there is currently a lack of basic knowledge regarding how this chemical works at the cellular level. We have recently discovered that acetylcholine produces opposing phasic and tonic actions on the excitability of brain cells in the cortex. The data collected in this study will reveal the receptor type, intracellular signalling pathways, and ionic mechanisms through which acetylcholine influences information processing in the brain. Together, these results will provide a framework for understanding the biological basis by which acetylcholine influences cognitive function. This new knowledge will in turn increase our understanding of why dysfunction of this important neurotransmitter system leads to the functional deficits observed in Alzheimer s Disease and other forms of dementia, and will hopefully suggest new targets for therapeutic intervention.Read moreRead less
The Contributions Of Different Sources Of Calcium To The Induction Of Long Term Potentiation
Funder
National Health and Medical Research Council
Funding Amount
$267,750.00
Summary
When we make memories, we alter the strength of synaptic connections between nerve cells.These changes are particularly marked in the hippopcampus ; a region of the brain involved in the formation of memories. The strength of a synaptic connection is altered if it activates a neurone sufficiently to cause a rise in the level of calcium ions. Calcium can be derived from several sources within the neurone. This project aims to assess the relative importance of these different sources of calcium in ....When we make memories, we alter the strength of synaptic connections between nerve cells.These changes are particularly marked in the hippopcampus ; a region of the brain involved in the formation of memories. The strength of a synaptic connection is altered if it activates a neurone sufficiently to cause a rise in the level of calcium ions. Calcium can be derived from several sources within the neurone. This project aims to assess the relative importance of these different sources of calcium in inducing increases in synaptic strength.Read moreRead less
Cognitive Enhancement In Schizophrenia Via Selective Oestrogen Receptor Modulator.
Funder
National Health and Medical Research Council
Funding Amount
$396,380.00
Summary
Cognitive dysfunction in schizophrenia is resistant to treatment and related to poor community functioning and quality of life. In spite of the widely appreciated magnitude of the problem, there is still a critical gap in our knowledge concerning treatments to reverse these cognitive deficits. The proposed research is significant because it will clarify the role of hormones and genes in relation to cognitive deficits in schizophrenia and it may help patients improve their level of functioning.
Brain Plasticity Following Changes In Sensory Input
Funder
National Health and Medical Research Council
Funding Amount
$312,576.00
Summary
The research proposed here will investigate the mechanisms our brains use to adapt to changes in sensory input, as occurs following blindness, deafness, nerve damage or loss of a limb. The information gathered will help develop treatments for diseases associated with sensory loss, as well as those associated with deficits in our ability to learn and remember, such as Alzheimer's disease.
Insulin-regulated Aminopeptidase, Glucose And Memory
Funder
National Health and Medical Research Council
Funding Amount
$555,693.00
Summary
We have previously shown that inhibitors of IRAP improve performance in memory tasks in normal and memory impaired animals and are currently developing new treatments for memory loss using IRAP as a target. In this study, we will investigate the physiological roles of IRAP and its association with intracellular proteins. The knowledge obtained will provide insights of how the brain process memory and confirm the suitability of IRAP inhibitors as drugs for treating memory deficits.