Identifying Target Genes For Novel Anti-epileptic Therapies In The Mouse
Funder
National Health and Medical Research Council
Funding Amount
$469,802.00
Summary
Epilepsy is a disease which affects 2-4% of the population. There are a wide range of drugs available to treat the condition but there is consistently 30-40% of patients who do not respond well to any of these drugs and who continue to have seizures. The reason that there are no drugs available for these people is that most of the drugs available have been designed along the same principles. A new set of principles is needed to develop new drugs which will be able to treat those people not respo ....Epilepsy is a disease which affects 2-4% of the population. There are a wide range of drugs available to treat the condition but there is consistently 30-40% of patients who do not respond well to any of these drugs and who continue to have seizures. The reason that there are no drugs available for these people is that most of the drugs available have been designed along the same principles. A new set of principles is needed to develop new drugs which will be able to treat those people not responding to current therapy. This project is designed to identify new biologic pathways which may be interrupted with drugs to prevent seizures in people with epilepsy. This project uses a procedure to induce mutations into genes in mice and then screens for mice which do not seize when challenged with a drug which generates seizures in mice. Genetic studies will identify the mutated genes and these will be used as potential targets for new therapies or will identify new biological pathway which should expand the use of future anti-epileptic drugs.Read moreRead less
The Role Of UPF3B And Nonsense Mediated MRNA Decay Surveillance In The Pathology Of Intellectual Disability.
Funder
National Health and Medical Research Council
Funding Amount
$789,954.00
Summary
Proper functioning of the nonsense mediated mRNA decay (NMD or 'mRNA police') is crucial for any cell to ensure normal development and function. When NMD is compromised the outcome is learning and memory problems, autism or schizophrenia. Under this project we study malfunctioning NMD using stem and neuronal cells derived from patients' skin cells. Some of the affected genes might be considered for therapeutic interventions. NMD is relevant to 1000s of human disorders and as such it is of fundam ....Proper functioning of the nonsense mediated mRNA decay (NMD or 'mRNA police') is crucial for any cell to ensure normal development and function. When NMD is compromised the outcome is learning and memory problems, autism or schizophrenia. Under this project we study malfunctioning NMD using stem and neuronal cells derived from patients' skin cells. Some of the affected genes might be considered for therapeutic interventions. NMD is relevant to 1000s of human disorders and as such it is of fundamental importance.Read moreRead less
About one in eight known genetic disorders involve DNA alteration that activates a cellular quality control mechanism that disables the affected gene. This mechanism is more efficient in some individuals than others. It can influence disease outcomes and severity. We will engineer and apply tools and models to measure and manipulate this crucial cellular mechanism. This will allow us to predict disease severity as well as to intervene where a manipulation of this mechanism will be beneficial.
Understanding marine biodiversity across vast spatial scales. Large-scale studies of biodiversity are frequently recommended by ecologists, but their costs are prohibitive. More efficient, yet accurate, sampling and analytical procedures are needed. This proposal will provide new quantitative knowledge on patterns of diversity of marine species (fish & invertebrates) from local to regional scales across southern Australia and northern New Zealand. An innovative feature of this research is the c ....Understanding marine biodiversity across vast spatial scales. Large-scale studies of biodiversity are frequently recommended by ecologists, but their costs are prohibitive. More efficient, yet accurate, sampling and analytical procedures are needed. This proposal will provide new quantitative knowledge on patterns of diversity of marine species (fish & invertebrates) from local to regional scales across southern Australia and northern New Zealand. An innovative feature of this research is the contribution of new ecological information with novel analytical procedures to identify the consequences of using more cost-effective techniques on quantifying patterns of biodiversity. This understanding is fundamental to the on-going advancement of ecology and conservation biology.Read moreRead less
Identification Of Genes For X-linked Mental Retardation.
Funder
National Health and Medical Research Council
Funding Amount
$675,228.00
Summary
We propose to identify novel heritable causes of intellectual disability using 22 large and well-characterised families from Australia. In these families we have refined the location of the genetic defect to the chromosome X and excluded the contribution of all so far known genes. We will achieve this using the technology of massive parallel sequencing. At the completion of the project we will have identified novel causes of intellectual disability and devised tests to identify them.
Genetic dissection of a regulatory deubiquitlyation network. The potential impact of this work is widespread, because although it is known that ubiquitlyation has regulatory consequences in multicellular eukaryotes, individual networks have not been completely described in higher eukaryotes. Knowledge gained about fundamental processes in the A. nidulans model system is directly applicable to fungi used in biotechnology in the food, beverage, enzyme and pharmaceutical production industries, and ....Genetic dissection of a regulatory deubiquitlyation network. The potential impact of this work is widespread, because although it is known that ubiquitlyation has regulatory consequences in multicellular eukaryotes, individual networks have not been completely described in higher eukaryotes. Knowledge gained about fundamental processes in the A. nidulans model system is directly applicable to fungi used in biotechnology in the food, beverage, enzyme and pharmaceutical production industries, and to fungal pathogens. Since the fungal genes that form the basis of this project are conserved in higher eukaryotes including humans, the knowledge will be transferable to these systems. A further benefit that cannot be overstated is the research education and training opportunities provided.
Read moreRead less
Forecasting change in subtidal habitats: connecting local pollution with global climate in temperate Australia. The current narrow focus of management on local and contemporary environmental conditions (e.g. water quality) has indeterminate outcomes in the face of climate change. This proposal seeks to forecast marine habitats under realistic scenarios of climate change and continuing local population growth and activity. This information provides managers with information needed to understand t ....Forecasting change in subtidal habitats: connecting local pollution with global climate in temperate Australia. The current narrow focus of management on local and contemporary environmental conditions (e.g. water quality) has indeterminate outcomes in the face of climate change. This proposal seeks to forecast marine habitats under realistic scenarios of climate change and continuing local population growth and activity. This information provides managers with information needed to understand the consequences of current policy and debates about its improvement.Read moreRead less
The interplay between natural and human perturbations in structuring marine habitats. Empirical predictions of which could be the changes to natural habitats caused by human perturbations will increase the ability to prevent irreversible losses of biodiversity. This project will enable the planning of sound strategies for the conservation of valuable ecosystems, such as kelp forests, in view of the massive changes that will likely take place as a consequence of increasing exploitation of marine ....The interplay between natural and human perturbations in structuring marine habitats. Empirical predictions of which could be the changes to natural habitats caused by human perturbations will increase the ability to prevent irreversible losses of biodiversity. This project will enable the planning of sound strategies for the conservation of valuable ecosystems, such as kelp forests, in view of the massive changes that will likely take place as a consequence of increasing exploitation of marine resources and of global climatic changes. The scientific knowledge generated by this project is necessary for a sustainable development of coastal areas, which would guarantee the provision of goods and services to Australian future generations.Read moreRead less
Local and regional investigations into perturbations of marine habitat. Surprising changes to coastal ecology are forecast as increasing physical stresses (e.g. nutrient and sediment runoff) initiate changes to habitat. Lack of information about perturbations remains a major gap in marine ecology and coastal management. Multifactorial experiments will examine perturbations to one of temperate Australia's most widespread subtidal habitats (kelp forests) to test predictions derived from ecologic ....Local and regional investigations into perturbations of marine habitat. Surprising changes to coastal ecology are forecast as increasing physical stresses (e.g. nutrient and sediment runoff) initiate changes to habitat. Lack of information about perturbations remains a major gap in marine ecology and coastal management. Multifactorial experiments will examine perturbations to one of temperate Australia's most widespread subtidal habitats (kelp forests) to test predictions derived from ecological theory. Tests focus on (1) models about abrupt switches of habitat to contrasting states, and (2) responses among regions bearing striking differences in consumer control. These trans-Australian tests may change the way we view one of the world's most extensive temperate coastlines.Read moreRead less
Managing Australia's unique south coast. Innovative coastal management based on sound ecological understanding is a pressing issue in state and federal government. A federal initiative seeks integration of marine protected areas with other spatial arrangements for conservation of biodiversity. This proposal will inform the forthcoming selection of marine protected areas in South Australia. Significantly, it assesses whether adjacent land-use (natural vegetation, urbanisation, agriculture) can ....Managing Australia's unique south coast. Innovative coastal management based on sound ecological understanding is a pressing issue in state and federal government. A federal initiative seeks integration of marine protected areas with other spatial arrangements for conservation of biodiversity. This proposal will inform the forthcoming selection of marine protected areas in South Australia. Significantly, it assesses whether adjacent land-use (natural vegetation, urbanisation, agriculture) can enhance or compromise the utility of marine protected areas as a biodiversity repository.
Read moreRead less