Characterisation Of Two Novel Markers Of Osteosarcoma Metastasis As Potential Therapeutic Targets
Funder
National Health and Medical Research Council
Funding Amount
$624,500.00
Summary
Osteosarcoma (OS) is the most common bone tumour in children and adolescents. In spite of aggressive chemotherapy, OS tumours that metastasise to the lungs result in dismal long-term survivals of only 10-20%. For these patients, new treatment options are desperately needed. In this proposal we show compelling data identifying two new markers of OS metastasis. This research aims to validate the suitability of these novel markers as therapeutic targets to prevent OS metastasis.
Targeting Drug-Resistance In Paediatric Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$649,048.00
Summary
Leukaemia is the most common type of cancer in children but resistance to therapy continues to be a significant problem. This project will investigate the biology of drug-resistance and relapse using a mouse model that replicates the human disease. We hope to identify novel therapeutic targets that can be used in combination with existing therapies to improve outcomes in this disease, particularly for patients that develop drug-resistance such as those at the time of relapse.
Ethics And Equity: Developing Ethical Guidance For Health Policy And Systems Research In Developing Countries
Funder
National Health and Medical Research Council
Funding Amount
$374,706.00
Summary
Health policy and systems research (HPSR) in developing countries is vital to achieving the Millennium Development goals, but ethical guidance specific to this field has not been developed. This project will identify the ethical obligations of funders, research institutions, and researchers undertaking HPSR in developing countries and will describe strategies for how these obligations might be upheld in practice.
A Study To Investigate Alternative Regimens For Pneumococcal Vaccination Of Infants In A Developing Country
Funder
National Health and Medical Research Council
Funding Amount
$1,622,210.00
Summary
Streptococcus pneumoniae (Pnc) is the leading vaccine preventable cause of serious infection in infants. The current Pnc conjugate vaccine is very expensive (approximately USD $200-infant) so it is unlikely to be affordable for most developing countries. Moreover, as health care access in developing countries may be episodic and unreliable, many children do not receive either complete or timely vaccine courses. Therefore, it is important to investigate affordable and flexible ways to deliver thi ....Streptococcus pneumoniae (Pnc) is the leading vaccine preventable cause of serious infection in infants. The current Pnc conjugate vaccine is very expensive (approximately USD $200-infant) so it is unlikely to be affordable for most developing countries. Moreover, as health care access in developing countries may be episodic and unreliable, many children do not receive either complete or timely vaccine courses. Therefore, it is important to investigate affordable and flexible ways to deliver this vaccine, which are safe and effective. A recent WHO-GAVI meeting to address impediments to the introduction of these vaccines in developing countries recognized the need to evaluate other regimens of Pnc conjugate vaccine as an important research priority. This study has been deliberately formulated with that need in mind. The site for this research is Fiji. Although health services are good, Pnc disease, particularly pneumonia, remains the commonest cause of childhood morbidity and mortality. Fiji has good vaccine coverage and was the first Pacific country to introduce Hib vaccine. The arrival of the new, expensive Pnc conjugate vaccine presents a dilemma for Fiji and many similar countries. The expense of this vaccine would consume a large portion of the health budget. This study has two components: 1. A Phase 2 immunogenicity study (involving 750 infants) to evaluate regimens using reduced numbers of doses of Pnc conjugate vaccine, and using timing of dosing and combinations with the Pnc polysaccharide (PS) vaccine that may be more suited to the epidemiology of Pnc disease in developing countries. 2. An epidemiological study will measure the burden of invasive Pnc disease and pneumonia in Fiji. This will be part of a global effort to address these issues, and will be used to develop rapid assessment tools for these diseases in developing countries. We will seek cofounding for this component.Read moreRead less
Understanding Cortical Circuitry Underlying Sensory Integration And The Consequence Of Its Developmental Disruption
Funder
National Health and Medical Research Council
Funding Amount
$527,395.00
Summary
The mammalian neocortex is organised into six layers with a systematic pattern of wiring that relies on normal development and balanced activity of neurons. This project combines developmental, electrophysiological, optogenetic behavioural, and computational methods to establish how the properties of the precise structure of cortical circuits impact their function and how disruptions in the balanced activity during development affect circuit formation and function in the mature brain.
The Claustrum Enigma: Unlocking The Role Of The Last Unknown Area Of The Primate Brain
Funder
National Health and Medical Research Council
Funding Amount
$558,364.00
Summary
Despite nearly 200 years of study, the function of the claustrum remains unclear. Interest in this brain structure has recently been revived by findings showing damage to the claustrum in several major diseases, and by the suggestion that the claustrum may have a role in consciousness. Here we propose a series of experiments to test the novel hypothesis that the claustrum is part of the default mode network, a group of brain areas that act together when we aren't thinking about anything in parti ....Despite nearly 200 years of study, the function of the claustrum remains unclear. Interest in this brain structure has recently been revived by findings showing damage to the claustrum in several major diseases, and by the suggestion that the claustrum may have a role in consciousness. Here we propose a series of experiments to test the novel hypothesis that the claustrum is part of the default mode network, a group of brain areas that act together when we aren't thinking about anything in particular, that is- most of the time.Read moreRead less
Dynamics of eigenvalue/eigenspace algorithms with applications to signal processing. Many problems in signal and systems lead naturally to an eigenvalue/eigenspace determination and tracking problem; for example (acoustic) echo-cancellation, crosstalk suppression in ADSL modems, direction of arrival determination with an array of sensors, linear system identification etc. Exploiting methods from global analysis and dynamical systems theory we will study the available algorithms for eigenspace de ....Dynamics of eigenvalue/eigenspace algorithms with applications to signal processing. Many problems in signal and systems lead naturally to an eigenvalue/eigenspace determination and tracking problem; for example (acoustic) echo-cancellation, crosstalk suppression in ADSL modems, direction of arrival determination with an array of sensors, linear system identification etc. Exploiting methods from global analysis and dynamical systems theory we will study the available algorithms for eigenspace determination to characterise their computational efficiency, accuracy and effectiveness in various data scenarios. The analysis will lead to improved designs for eigenvalue/eigenspace algorithms, as well as design tools to engineer algorithms to specific situations.Read moreRead less
Sparse grid approximations and fitting using generalised combination techniques. Sparse grid techniques provide an effective tool to deal with the
computational curse of dimensionality which is a constant challenge in
modelling complex data. The proposed research is aimed at the
development and analysis of algorithms for data fitting with sparse
grids using variants of the combination technique. The outcome of the
research is a theory which will provide insights in the applicability,
limit ....Sparse grid approximations and fitting using generalised combination techniques. Sparse grid techniques provide an effective tool to deal with the
computational curse of dimensionality which is a constant challenge in
modelling complex data. The proposed research is aimed at the
development and analysis of algorithms for data fitting with sparse
grids using variants of the combination technique. The outcome of the
research is a theory which will provide insights in the applicability,
limitations and the convergence properties of the proposed
algorithms. The outcomes will be widely applicable in modelling of
large scale and complex data as is encountered in areas of
bioinformatics, physics and experimental studies of complex systems.
Read moreRead less
Neuronal Substrate Of Choice In The Rat Whisker System
Funder
National Health and Medical Research Council
Funding Amount
$405,851.00
Summary
Humans and other animals can optimise their goal-directed behaviour by linking stimuli or actions to consequent positive and negative rewards. How does an animal generate such associations, and make decisions in the natural environment where the associations are often uncertain, at times contradictory, and continuously changing? This project uses rat whisker system as an animal model to identify the neuronal basis of perceptual decision making and the role of context.
Characterising Post Stroke Neuroplasticity In Humans – Identifying A Critical Window For Rehabilitation
Funder
National Health and Medical Research Council
Funding Amount
$764,419.00
Summary
Despite major investment in care for stroke patients, almost all have persisting disability. Stroke causes loss of brain cells that cannot be replaced. Some recovery is possible through compensatory mechanisms. In addition, intact cells around the stroke undergo growth that is critical for recovery. Animal studies suggest these changes take place in a “critical window” after stroke. Applying therapies in this window should improve outcomes. We will use novel approaches to define the “critical wi ....Despite major investment in care for stroke patients, almost all have persisting disability. Stroke causes loss of brain cells that cannot be replaced. Some recovery is possible through compensatory mechanisms. In addition, intact cells around the stroke undergo growth that is critical for recovery. Animal studies suggest these changes take place in a “critical window” after stroke. Applying therapies in this window should improve outcomes. We will use novel approaches to define the “critical window” in patients after strokeRead moreRead less