Single minded 1 in neuron development and satiety signalling. An understanding of how Single minded 1 (SIM1) regulates target genes may allow new pharmaceutical approaches to be designed to combat obesity. As Sim1 belongs to a family of closely related gene regulatory proteins which function in early development and homeostasis, deciphering the molecular control mechanisms of Sim1 may help understand how the related factors function in processes such as angiogenesis, response to low oxygen stres ....Single minded 1 in neuron development and satiety signalling. An understanding of how Single minded 1 (SIM1) regulates target genes may allow new pharmaceutical approaches to be designed to combat obesity. As Sim1 belongs to a family of closely related gene regulatory proteins which function in early development and homeostasis, deciphering the molecular control mechanisms of Sim1 may help understand how the related factors function in processes such as angiogenesis, response to low oxygen stress, invasion of environmental pollutants and autism spectrum diseases. The ability to manipulate these factors would be of great benefit in treating a range of disorders, but a thorough molecular understanding of these factors needs be obtained prior to attempting design of pharmaceuticals.Read moreRead less
Innovative Approaches for Defining the Interaction of Insulin like Growth Factor I (IGF I) with the Type 1 IGF Receptor. This study will improve our understanding of the interactions of Insulin-like Growth Factors (IGFs) with their principal receptor, the IGF-1R. A sound understanding of these interactions is essential for the development of non-peptide IGF antagonists designed for therapeutic applications. Such molecules could lead to new therapeutic approaches for diseases in which dysregul ....Innovative Approaches for Defining the Interaction of Insulin like Growth Factor I (IGF I) with the Type 1 IGF Receptor. This study will improve our understanding of the interactions of Insulin-like Growth Factors (IGFs) with their principal receptor, the IGF-1R. A sound understanding of these interactions is essential for the development of non-peptide IGF antagonists designed for therapeutic applications. Such molecules could lead to new therapeutic approaches for diseases in which dysregulation of the IGF system has been implicated including cancer, diabetes and atherosclerosis.
Since IGFs are major determinants of growth, the outcomes of this project could also lead to improvements in animal production with major benefit to primary industry. New IGF analogues developed could assist biotechnology exports.
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New Insights into the Structure and Function of Pyruvate Carboxylase. Pyruvate carboxylase plays an essential roles in insulin secretion by pancreatic islets and in normal brain function, but excess expression of this enzyme in liver and adipose tissue is associated with diabetes and obesity.
Understanding the function of each structural feature in the reaction mechanism of an enzyme is essential to designing safe and effective pharmaceuticals that are required to modulate its activity.
Th ....New Insights into the Structure and Function of Pyruvate Carboxylase. Pyruvate carboxylase plays an essential roles in insulin secretion by pancreatic islets and in normal brain function, but excess expression of this enzyme in liver and adipose tissue is associated with diabetes and obesity.
Understanding the function of each structural feature in the reaction mechanism of an enzyme is essential to designing safe and effective pharmaceuticals that are required to modulate its activity.
This project, which will use cutting edge techniques in an experimental model, seeks to characterise this important enzyme's function so that better treatments can be developed in future for diabetes and obesity.
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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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Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0668241
Funder
Australian Research Council
Funding Amount
$824,610.00
Summary
A Facility for High-Throughput, Functional Gene Discovery Using Arrayed Retroviral Expression Cloning. The proposed facility will represent world-leading technology in functional genomics and provide Australian scientists with unique opportunities to identify genes involved in a broad range of biological processes. This will contribute to fundamental knowledge in mammalian biology, and equally importantly, is likely to identify genes involved in important health problems such as cancer, inflamma ....A Facility for High-Throughput, Functional Gene Discovery Using Arrayed Retroviral Expression Cloning. The proposed facility will represent world-leading technology in functional genomics and provide Australian scientists with unique opportunities to identify genes involved in a broad range of biological processes. This will contribute to fundamental knowledge in mammalian biology, and equally importantly, is likely to identify genes involved in important health problems such as cancer, inflammatory disease, brain damage and diabetes. Such genes may in turn constitute targets against which new therapies may be developed. This endeavour will contribute to national research priorities in both the health and scientific/technological development arenas.Read moreRead less
Foundations for a Cognitive Biology. Understanding cognition has important implications for individual and social wellbeing and thus for the nation's economic health. Until the many disciplines concerned with cognition can effectively integrate their disparate findings, public investment in cognitive research will not yield benefits to its potential. The project aims to produce a coherent model of cognition that will facilitate new cross-disciplinary approaches to research, thereby improving Aus ....Foundations for a Cognitive Biology. Understanding cognition has important implications for individual and social wellbeing and thus for the nation's economic health. Until the many disciplines concerned with cognition can effectively integrate their disparate findings, public investment in cognitive research will not yield benefits to its potential. The project aims to produce a coherent model of cognition that will facilitate new cross-disciplinary approaches to research, thereby improving Australia's means of promoting and maintaining healthy cognitive function and treating cognitive dysfunction.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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0989336
Funder
Australian Research Council
Funding Amount
$560,000.00
Summary
The South Australian Facility for Small and Large Molecule X-Ray Diffraction Structure Determination. The precise three dimensional arrangement of atoms within molecular and macromolecular structures defines their function. Thus, the discovery, development and application of biological compounds, catalysts, nanodevices and pharmaceuticals require X-ray diffraction structure determination. These endeavours underpin the conversion of academic research into real benefits for the community and are ....The South Australian Facility for Small and Large Molecule X-Ray Diffraction Structure Determination. The precise three dimensional arrangement of atoms within molecular and macromolecular structures defines their function. Thus, the discovery, development and application of biological compounds, catalysts, nanodevices and pharmaceuticals require X-ray diffraction structure determination. These endeavours underpin the conversion of academic research into real benefits for the community and are critical for the competitiveness of Australian industry, national productivity and economic growth. This application seeks to provide a facility for multidisciplinary scientific development that will enhance academic-industrial collaboration. This will position SA research community for scientific breakthroughs that benefit the Australian community.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