Regulated muscle-based thermogenesis for body temperature regulation. Mammals maintain a constant core body temperature by generating heat in resting muscles in response to changes in the environmental temperatures. This project aims to show how the skeletal muscles that are closer to the body core contribute the majority of heat, how the muscles of the limbs have their heat generation curtailed as necessary, and how this is coordinated by the body in response to ambient temperature. Project out ....Regulated muscle-based thermogenesis for body temperature regulation. Mammals maintain a constant core body temperature by generating heat in resting muscles in response to changes in the environmental temperatures. This project aims to show how the skeletal muscles that are closer to the body core contribute the majority of heat, how the muscles of the limbs have their heat generation curtailed as necessary, and how this is coordinated by the body in response to ambient temperature. Project outcomes include defining, for the first time, how heat generation in the muscles of the body is regulated. This should provide critical knowledge of mammalian evolution and ways to manipulate metabolism, which may provide ways to assist the production of meat by managing hypothermia and hyperthermia risk in agriculture.Read moreRead less
Molecular control of postnatal heart development. This project aims to improve our understanding of how the heart develops after birth and the molecules that control this process. Recent advances in tissue engineering have opened up opportunities for the generation of synthetic tissues but these studies have also highlighted a fundamental knowledge gap in our understanding of how complex tissues mature to prepare for life as an adult. Much is known about the molecules that control early embryoni ....Molecular control of postnatal heart development. This project aims to improve our understanding of how the heart develops after birth and the molecules that control this process. Recent advances in tissue engineering have opened up opportunities for the generation of synthetic tissues but these studies have also highlighted a fundamental knowledge gap in our understanding of how complex tissues mature to prepare for life as an adult. Much is known about the molecules that control early embryonic development but little is known about the molecules that control maturation after birth. This project aims to build new knowledge that is expected to improve our ability to generate mature heart muscle cells for stem cell applications, tissue repair and regeneration.Read moreRead less
Muscle fibre excitability and calcium regulation in skeletal muscle of amphibians and mammals. The fundamental role of skeletal muscle is posture and movement. Essential for this is a specialised cell structure and a complex regulation of function. This project will define key aspects of muscle structure and functional regulation crucial to developing targets for improving function under stressed states such as fatigue, disease and age.
Calcium cycling and heat generation in skeletal muscle fibres. This project aims to uncover the mechanisms that enable mammalian skeletal muscle to play a major role in generating the heat required to maintain a constant body temperature. The ability to modulate body heat played a defining role in the evolution of species, their behaviour and global distribution. How heat production occurs in resting muscle is of fundamental importance and will be defined for the first time, providing new avenu ....Calcium cycling and heat generation in skeletal muscle fibres. This project aims to uncover the mechanisms that enable mammalian skeletal muscle to play a major role in generating the heat required to maintain a constant body temperature. The ability to modulate body heat played a defining role in the evolution of species, their behaviour and global distribution. How heat production occurs in resting muscle is of fundamental importance and will be defined for the first time, providing new avenues to manipulate metabolic rate and counter obesity.Read moreRead less
Gut Absorption of Constrained Peptides for Local and Systemic Targeting. Aims: This project aims to investigate how peptides are absorbed across the intestinal wall and distributed to organs and fluids in a rodent model by combining bio-analysis and pharmacokinetics with high-resolution microscopy and imaging.
Significance: This project expects to generate the most comprehensive survey to date of the pathways and mechanisms of peptide absorption, biodistribution and immune cell targeting, by ....Gut Absorption of Constrained Peptides for Local and Systemic Targeting. Aims: This project aims to investigate how peptides are absorbed across the intestinal wall and distributed to organs and fluids in a rodent model by combining bio-analysis and pharmacokinetics with high-resolution microscopy and imaging.
Significance: This project expects to generate the most comprehensive survey to date of the pathways and mechanisms of peptide absorption, biodistribution and immune cell targeting, by implementing innovative approaches.
Expected Outcomes: Expected outcomes include significant new knowledge and a new multi-disciplinary platform for measuring peptide absorption.
Benefits: This should provide significant benefits by informing the future design of peptides for supplements, therapeutics and carriers. 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