Proteomic analysis of central nervous system inflammation in multiple sclerosis. This project aims to identify new therapeutic targets and diagnostics for Multiple Sclerosis (MS) the most common neurological disease in young adults. The estimated economic burden of this disease in Australia is around $2 billion per annum. There is also a large social cost to take into account. In spite of a great deal of research, current therapies are limited. We expect that this this research will: lead to n ....Proteomic analysis of central nervous system inflammation in multiple sclerosis. This project aims to identify new therapeutic targets and diagnostics for Multiple Sclerosis (MS) the most common neurological disease in young adults. The estimated economic burden of this disease in Australia is around $2 billion per annum. There is also a large social cost to take into account. In spite of a great deal of research, current therapies are limited. We expect that this this research will: lead to new therapies and better diagnostics, which will reduce the financial and human cost of this disease; generate IP with subsequent economic benefits and; expand proteomics technologies which will have flow on effects including economic benefits and benefits to a wide range of basic research. Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0453073
Funder
Australian Research Council
Funding Amount
$129,485.00
Summary
Establishment of a South Australian rTMS Facility. It is proposed to establish a South Australian Facility for rapid rate transcranial magnetic stimulation (TMS) which will be the only one in Australia. This Facility will provide enormous opportunities for collaborative cutting edge investigations into the role of the human cortical areas in a diverse range of tasks. For example, projects have been identified projects employing rTMS to study sensorimotor cortical plasticity, facilitate functiona ....Establishment of a South Australian rTMS Facility. It is proposed to establish a South Australian Facility for rapid rate transcranial magnetic stimulation (TMS) which will be the only one in Australia. This Facility will provide enormous opportunities for collaborative cutting edge investigations into the role of the human cortical areas in a diverse range of tasks. For example, projects have been identified projects employing rTMS to study sensorimotor cortical plasticity, facilitate functional recovery following stroke and investigate the mechanisms of savant behaviour. Provision of this Facility will provide further support for this productive and internationally renowned group of scientists to develop their research programs.Read moreRead less
Afferent stimulation-induced plasticity and its functional significance. Certain regions of the brain can reorganise (plasticity) during motor learning or when there is damage to peripheral nerves or muscles. There is a large body of evidence for these plastic changes in animals. Until recently data showing that similar changes occurred in humans was limited. However, we have recently demonstrated that certain patterns of peripheral stimulation can indeed induce similar changes in human subjects ....Afferent stimulation-induced plasticity and its functional significance. Certain regions of the brain can reorganise (plasticity) during motor learning or when there is damage to peripheral nerves or muscles. There is a large body of evidence for these plastic changes in animals. Until recently data showing that similar changes occurred in humans was limited. However, we have recently demonstrated that certain patterns of peripheral stimulation can indeed induce similar changes in human subjects. These findings are important for our understanding of the mechanisms of motor control and learning.Read moreRead less
Communication and information storage mechanisms in complex dynamical brain networks. Recordings of electrical activity in the brain often cycle repetitively. The aim of this research is to explain how these brain rhythms assist the brain to coordinate simultaneous activity in several regions. Australian socioeconomic benefits include: (i) contributions to the knowledge base of theoretical neuroscience, enhancing Australia's reputation for cutting-edge research; (ii) strengthening of internation ....Communication and information storage mechanisms in complex dynamical brain networks. Recordings of electrical activity in the brain often cycle repetitively. The aim of this research is to explain how these brain rhythms assist the brain to coordinate simultaneous activity in several regions. Australian socioeconomic benefits include: (i) contributions to the knowledge base of theoretical neuroscience, enhancing Australia's reputation for cutting-edge research; (ii) strengthening of international collaborations with Europe and Japan; (iii) outcomes will ultimately impact on improved medical bionics and future interfaces between brain activity and machines or computers; and (iv) commercialization and technology transfer opportunities, via the transfer of results to biologically inspired engineering.Read moreRead less
The role of the neuronal Hu proteins in the regulation of the BMP signalling pathway. We aim to understand the critical decision of a neural progenitor to commit to becoming a neuron. The BMP signalling pathway is central in this decision. Neural progenitors appear to become insensitive to BMP signals, and this lack of signalling leads to neuronal differentiation. We hypothesise that neuronal identity is regulated by an unusual genetic switch- the translational regulation by the neuronal Hu pr ....The role of the neuronal Hu proteins in the regulation of the BMP signalling pathway. We aim to understand the critical decision of a neural progenitor to commit to becoming a neuron. The BMP signalling pathway is central in this decision. Neural progenitors appear to become insensitive to BMP signals, and this lack of signalling leads to neuronal differentiation. We hypothesise that neuronal identity is regulated by an unusual genetic switch- the translational regulation by the neuronal Hu proteins of two proteins in the BMP pathway. Verification of a post-transcriptional regulatory mechanism for cell fate determination would be a major discovery, and may prompt investigation of how to harness the neuron-inducing function of the Hu proteins to address the therapeutic need for new neurons in neurologic diseases.Read moreRead less
The basis of recognition and disposal of dysfunctional proteins by clusterin. When proteins become damaged they can precipitate. A blood protein called clusterin prevents precipitation of damaged proteins. Clusterin does this by forming complexes with the damaged proteins. Clusterin is the first blood protein known to do this. We will discover which parts of clusterin are responsible for this activity. We will also discover whether cells can take up and dispose of the complexes of clusterin and ....The basis of recognition and disposal of dysfunctional proteins by clusterin. When proteins become damaged they can precipitate. A blood protein called clusterin prevents precipitation of damaged proteins. Clusterin does this by forming complexes with the damaged proteins. Clusterin is the first blood protein known to do this. We will discover which parts of clusterin are responsible for this activity. We will also discover whether cells can take up and dispose of the complexes of clusterin and damaged proteins. This work is important because some diseases (eg, Alzheimers disease) involve the toxic effects of abnormal protein precipitation. Understanding how clusterin works may help in developing better treatments for these diseases.Read moreRead less
Phylogeny and radiation of flatworm ectoparasites from marine fish using morphology and genetics, with novel approaches to identify pathogenic species. Fish flukes (flatworm parasites) with direct lifecycles can weaken and kill captive fish and threaten lucrative industries like finfish aquaculture and public aquaria in Australia and globally. Traditional approaches and molecular techniques will identify monogenean flukes in a family containing known pathogenic species distributed worldwide. K ....Phylogeny and radiation of flatworm ectoparasites from marine fish using morphology and genetics, with novel approaches to identify pathogenic species. Fish flukes (flatworm parasites) with direct lifecycles can weaken and kill captive fish and threaten lucrative industries like finfish aquaculture and public aquaria in Australia and globally. Traditional approaches and molecular techniques will identify monogenean flukes in a family containing known pathogenic species distributed worldwide. Knowledge of fish disease is paramount for quarantine, risk assessments for import/export and for managing pathogen outbreaks in aquaculture. Benefits include: economic/social improvements in regional/rural Australia where fish farms are expanding; international excellence and core research training in fish parasitology; profitable, exportable expertise; knowledge of endemic and shared pathogens.Read moreRead less
Cell-free immune reactions and suppression. Insects pests and insect vectors of diseases are managed by toxic substances, but insects have a cunning ability to persist. How pesticide-tolerant insect pests recognise and inactivate chemical and biological toxins is poorly understood. While vertebrates with a closed circulatory system use coagulation reactions mainly for wound-healing, invertebrates employ cell-free aggregation reactions for the sequestration and inactivation of potentially damagin ....Cell-free immune reactions and suppression. Insects pests and insect vectors of diseases are managed by toxic substances, but insects have a cunning ability to persist. How pesticide-tolerant insect pests recognise and inactivate chemical and biological toxins is poorly understood. While vertebrates with a closed circulatory system use coagulation reactions mainly for wound-healing, invertebrates employ cell-free aggregation reactions for the sequestration and inactivation of potentially damaging objects and substances. We use insect plasma to dissect recognition and inactivation of damaging objects and substances with the aim to understand tolerance and its inhibition to design novel strategies in delaying tolerance to pesticides in insect pests.Read moreRead less
The puzzle of Metazoan life history evolution: are feeding larvae always primitive? Most marine animals have a complex life-cycles with alternating pelagic larvae and benthic adults. An theory about animal life-history evolution states that feeding larvae are always primitive and larval feeding is lost but not gained. This hypothesis is based in part on studies on the 'classical' trochophore of marine worms such as Serpulidae, a group with both feeding and non-feeding larvae. We intend to establ ....The puzzle of Metazoan life history evolution: are feeding larvae always primitive? Most marine animals have a complex life-cycles with alternating pelagic larvae and benthic adults. An theory about animal life-history evolution states that feeding larvae are always primitive and larval feeding is lost but not gained. This hypothesis is based in part on studies on the 'classical' trochophore of marine worms such as Serpulidae, a group with both feeding and non-feeding larvae. We intend to establish a detailed phylogeny for Serpulidae and assess the evolution of larvae in the group. If feeding larvae are shown to be secondary this will raise doubts about established theories of animal evolution.Read moreRead less
Structural and Functional Aspects of the Allosteric Regulation of Pyruvate Carboxylase by Acyl-CoA Compounds. Pyruvate carboxylase occupies a central location in intermediary metabolism catalysing the formation of oxaloacetate, a key component of the Krebs' tricarboxylic acid cycle especially in its synthetic modes in gluconeogenesis, lipogenesis and in the synthesis of neurotransmitters.
This project aims: (i) To produce crystals of pyruvate carboxylase for determining its structure by X-ra ....Structural and Functional Aspects of the Allosteric Regulation of Pyruvate Carboxylase by Acyl-CoA Compounds. Pyruvate carboxylase occupies a central location in intermediary metabolism catalysing the formation of oxaloacetate, a key component of the Krebs' tricarboxylic acid cycle especially in its synthetic modes in gluconeogenesis, lipogenesis and in the synthesis of neurotransmitters.
This project aims: (i) To produce crystals of pyruvate carboxylase for determining its structure by X-ray diffraction; (ii) To use affinity-labelling to determine the amino acid residues in the binding site of the enzyme's allosteric activator, acetyl-CoA; (iii) To construct chimeric enzymes from different species to define regions of the enzyme which affect its responses to its important allosteric activator, acetyl-CoA.
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