Harnessing Tyrosine Metabolism To Combat Respiratory Diseases
Funder
National Health and Medical Research Council
Funding Amount
$866,467.00
Summary
Cross-talk between our immune system and the microbiome is central to health and disease. In particular, the gut microbiome has wide-ranging effects throughout the body, in part through the production of metabolites with immunomodulatory activity. We have discovered a novel subset of microbial metabolites which can protect mice against allergic airway inflammation, a model of asthma. We now aim to discovery how these metabolites work with a view towards developing them as therapeutics.
The dramatic increase in obesity and age-related metabolic disorders demonstrates the importance of gaining a better understanding of how cells and organisms regulate their energy stores. This project will identify novel molecular mechanisms that control the enzyme CaMKK2, which is a key regulator of whole-body energy metabolism. This will provide new opportunities to inform more effective strategies to tackle metabolic diseases, and improve health in an increasingly ageing population.
Age-related mechanisms of amino acid signalling in skeletal muscle. This project aims to increase our understanding of the role of glycine receptor-mediated signalling and its metabolism in the amino acid sensing capacity of mTORC1, a key enzyme regulating muscle protein synthesis. Ageing is associated with a progressive decline in skeletal muscle mass, weakness, and impaired regeneration after injury. Impaired anabolic signalling after food intake has been proposed as a key contributor, yet the ....Age-related mechanisms of amino acid signalling in skeletal muscle. This project aims to increase our understanding of the role of glycine receptor-mediated signalling and its metabolism in the amino acid sensing capacity of mTORC1, a key enzyme regulating muscle protein synthesis. Ageing is associated with a progressive decline in skeletal muscle mass, weakness, and impaired regeneration after injury. Impaired anabolic signalling after food intake has been proposed as a key contributor, yet the metabolic pathways responsible for nutrient sensing and regulation of protein synthesis remain unresolved. The project will assess defective amino acid sensing and protein synthesis in old mammals, identifying the role of glycine signalling in these processes. The project expects to underpin development of muscle-specific modulators of muscle homeostasis with broad relevance to Australia’s ageing population.Read moreRead less
The “New” Biochemistry of Polyamines: When Metabolic Pathways Collide. Basic biochemistry and the metabolic regulation of proliferation remain as the fundamental building blocks of knowledge in cell biology that have enabled breakthrough advances in biology and medicine. Polyamines are unique and ubiquitous low-Mr amines that play vital roles in many biological processes, including proliferation, DNA/RNA synthesis, etc. This proposal will mechanistically dissect the "new" biochemistry of polyami ....The “New” Biochemistry of Polyamines: When Metabolic Pathways Collide. Basic biochemistry and the metabolic regulation of proliferation remain as the fundamental building blocks of knowledge in cell biology that have enabled breakthrough advances in biology and medicine. Polyamines are unique and ubiquitous low-Mr amines that play vital roles in many biological processes, including proliferation, DNA/RNA synthesis, etc. This proposal will mechanistically dissect the "new" biochemistry of polyamines, as we have discovered that polyamines are regulated by iron at 2-major levels, involving >10-key polyamine pathway proteins. This proposal represents first-in-field studies specifically designed to dissect mechanisms involved in this relationship. Our Central Hypothesis is that iron regulates polyamine metabolism.Read moreRead less
Defining the cellular impacts of protein aggregation in neurodegenerative disease with an aggreomics platform. The brain disease Huntington’s is caused by abnormally shaped proteins that assemble into toxic clusters. This project will design new bioprobes to track how these clusters form and cause damage to cells. This strategy will also provide new opportunities for discovering novel therapeutic targets.