Interdisciplinary Insights Into The Rational Design Of Malaria Therapy And Vaccines
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Malaria is a global health concern with almost half a million deaths annually. There is an urgent need for a highly effective malaria vaccine and new antimalarials. However, despite decades of research into this pathogen, our understanding of what causes illness in a person and how immunity operates is limited. This project will use a mathematical modelling approach to provide a new way to understand infection, as a rapidly changing and intricate process.
Improved Perception Of Temporal Information In Electrical Signals For Profoundly Deaf Users Of Cochlear Implants
Funder
National Health and Medical Research Council
Funding Amount
$170,440.00
Summary
The ultimate goal of this project is to improve the ability of cochlear implant users to understand speech. The way in which a speech signal varies in amplitude over time provides useful information to the listener about the content of the speech signal. Currently, the way that the acoustic signal amplitude is converted to electrical signal amplitude for cochlear implantees does not take into consideration the very significant loudness summation present in multiple-electrode electrical stimulati ....The ultimate goal of this project is to improve the ability of cochlear implant users to understand speech. The way in which a speech signal varies in amplitude over time provides useful information to the listener about the content of the speech signal. Currently, the way that the acoustic signal amplitude is converted to electrical signal amplitude for cochlear implantees does not take into consideration the very significant loudness summation present in multiple-electrode electrical stimulation. That is, when there are multiple sequential current pulses on different electrodes over a short time, the resultant loudness is greater than the loudness due to individual current pulses. The lack of consideration of loudness summation effects has led to the amplitude variations in the acoustic signal not being accurately represented in the loudness variation perceived by the cochlear implantee. This project aims to develop a practical way of more accurately representing speech signal amplitude fluctuations for cochlear implantees by studying the effects of loudness summation. A second aim of the project is to study the effects on perception of using differently-shaped current pulses from those currently used. There is evidence from physiology experiments that using different shapes might cause the electrical stimulation to activate a more narrowly-spaced set of auditory neurons for each electrode. The application of results of both these studies will lead directly to improved perception of speech and other sounds by cochlear implantees, thus improving their communication ability and quality of life.Read moreRead less
Prevalence And Characterisation Of FMR1 Gene's Premutation Carriers Amongst Older Males Presenting With Tremor/ataxia
Funder
National Health and Medical Research Council
Funding Amount
$199,450.00
Summary
The study concerns a novel form of progressive neurological disorder associated with tremor and body imbalance occurring in older males and caused by a small expansion of the trinucleotide (CGG) repeat in a fragile X (FMR1) gene. This expansion is termed 'premutation', in contrast with the full mutation, where a large expansion of the CGG repeat in this gene causes Fragile X Syndrome, a common form of intellectual disability. While brain anomaly in the full mutation is caused by a deficit of the ....The study concerns a novel form of progressive neurological disorder associated with tremor and body imbalance occurring in older males and caused by a small expansion of the trinucleotide (CGG) repeat in a fragile X (FMR1) gene. This expansion is termed 'premutation', in contrast with the full mutation, where a large expansion of the CGG repeat in this gene causes Fragile X Syndrome, a common form of intellectual disability. While brain anomaly in the full mutation is caused by a deficit of the FMR1 specific protein product (FMRP), the pathways from premutation to a neurological disorder are unknown. In this disorder, neurological dysfunction is associated with brain atrophy visible in magnetic resonance (MRI) images. Molecular studies showed increased levels of 'messenger' RNA (mRNA), which indicates overexpression of FMR1 gene . Our own study showed significantly increased (41.7%) prevalence of neurological involvement in male premutation carriers aged >50, compared with age-matched norms. Moreover, a screening of patients with two neurological disorders associated with tremor showed a significant increase of premutation carriers (5%- 22%). The aim of this study is to test hypotheses about the association of late-onset neurological disorders of unknown cause presenting tremor and imbalance, with a fragile X premutation in males, by screening for the presence of this premutation; and then conducting a full assessment of the identified premutation carriers, including detailed neurological, neuropsychological and MRI tests, to establish the spectrum of neurological involvement. This involvement will be correlated with the molecular (DNA, mRNA, FMRP) findings. The results will contribute to understanding the mechanisms of neurological involvement caused by this premutation. Moreover, estimation of the prevalence of this premutation in relevant neurological disorders will impact on standard diagnostic, and possibly future treatment approaches in neurology clinics.Read moreRead less
Dominant Repeat Expansion Diseases - A Common RNA Mediated Pathogenic Pathway?
Funder
National Health and Medical Research Council
Funding Amount
$281,118.00
Summary
There are fourteen human genetic diseases that are caused by a similar mutation mechanism and have similar clinical outcomes - the loss of function, degeneration and eventual death of nerve cells. This group of diseases includes Huntington's Disease. They are transmitted from parent to offspring such that each child of an affected parent has 50% risk of inheriting the affected gene and therefore developing the disease. The symptoms of these diseases typically develop later in life - between the ....There are fourteen human genetic diseases that are caused by a similar mutation mechanism and have similar clinical outcomes - the loss of function, degeneration and eventual death of nerve cells. This group of diseases includes Huntington's Disease. They are transmitted from parent to offspring such that each child of an affected parent has 50% risk of inheriting the affected gene and therefore developing the disease. The symptoms of these diseases typically develop later in life - between the ages of 35 and 50 years. While the different genes for these diseases have been identified the pathways that lead from their similar form of mutation to their similar clinical outcomes are not yet understood. Some evidence suggests that certain of these diseases have a common toxic component but this component is not shared by all of the disease genes and so an additional agent that they have in common is being sought. This research will use a genetic model organism - the vinegar fly, Drosophila melanogaster, to test the identity of a good candidate (RNA) for a common toxic agent and to provide information about the pathway by which RNA leads to nerve cell degeneration and death. Accurate and complete knowledge of the identity and composition of the pathways that lead from the mutation to the disease are crucial for correct target identification in the development of drug leads.Read moreRead less
RNA-based Expanded Repeat Pathogenic Pathway In Neurodegenerative Diseases
Funder
National Health and Medical Research Council
Funding Amount
$595,153.00
Summary
Many important human genetic diseases (incl Huntington’s Disease) are due to a common mutation mechanism with some similarities in clinical outcome (late in life nerve cell loss). For these diseases it is still not known what mechanism is responsible for causing the disease. This is essential in order to delay onset, slow progression or effect cure. We will test a mechanism for disease pathology that we have identified in a simple model organism and seen evidence of its activity in human disease
Understanding Influenza Mortality And The Effects Of Vaccination In The Elderly
Funder
National Health and Medical Research Council
Funding Amount
$446,877.00
Summary
We will analyse mortality from influenza and other causes to estimate the numbers of deaths from other causes that are triggered by influenza in elderly persons, and to test the value of vaccination in preventing those deaths. Our results will help to decide whether an expensive clinical trial is really needed to show the benefit of influenza vaccination on all-cause mortality in the elderly.
Dynamic Aspects Of Inhibitory Synaptic Transmission And Modulation By Neuroactive Drugs
Funder
National Health and Medical Research Council
Funding Amount
$370,500.00
Summary
Information moving through the brain is typically encoded as brief bursts of signals. These signals travel along the microscopic wiring that connect the brain's nerve cells into complex circuits. Information is encoded in the frequency of the signals within a burst, and the duration of each burst. This frequency-coded information is processed at the contact points between nerve cells (synapses). Almost all neuroactive drugs target synapses, where they alter information processing. Most of the in ....Information moving through the brain is typically encoded as brief bursts of signals. These signals travel along the microscopic wiring that connect the brain's nerve cells into complex circuits. Information is encoded in the frequency of the signals within a burst, and the duration of each burst. This frequency-coded information is processed at the contact points between nerve cells (synapses). Almost all neuroactive drugs target synapses, where they alter information processing. Most of the information about how neuroactive drugs work has been acquired from experiments performed under steady-state conditions. Typically, drugs are applied at a constant concentration and a synapse is stimulated at an unrealistically low frequency. The data obtained under these conditions are very useful, but tell only part of the story. For example, during an extended burst of signals, some neuroactive drugs may be displaced from their synaptic binding sites, reducing their effectiveness. In contrast, other drugs can only bind when synapses are active, and their effectiveness will increase during a burst of signals. For optimal drug design and delivery, it is important to understand how drugs work during bursts of activity. To date, the highly dynamic, non-equilibrium conditions encountered at central synapses have not been extensively studied. The central goal of this research proposal is to investigate the dynamic properties of synapses, and the drugs that modulate them. The results will provide insights into information processing in the brain, and will have significant implications for the development and targeting of clinically relevant neuropharmacological compounds.Read moreRead less
A reduced capacity to recover balance following an imbalance episode contributes to the high incidence of falls in older adults. The goal of the present study is to determine how age-related differences in lower extremity neuromuscular and biomechanical properties are related to balance recovery capacity and falls incidence. A detailed understanding of this relationship is necessary for the development of efficacious exercise-based interventions for the prevention of falls.