A Structural Understanding Of Class B G Protein-coupled Receptor Function
Funder
National Health and Medical Research Council
Funding Amount
$1,289,570.00
Summary
G protein-coupled receptors (GPCRs) are the largest family of cell surface proteins that enable communication from external signals to the inside of cells of the body. Class B GPCRs are a therapeutically important subclass of these receptors and they play crucial roles in bone and energy homeostasis, cardiovascular control and immune response. This grant will uncover fundamental knowledge on how these receptors work, and will enhance future development of therapeutics.
Signaling Pathways To Enhance Potency Of AMPK-targeting Drugs
Funder
National Health and Medical Research Council
Funding Amount
$661,966.00
Summary
Sedentary lifestyles and consumption of high energy foods has led to epidemics of obesity-related metabolic diseases that place enormous financial and medical burden on the Australian economy. An attractive drug target to treat these diseases is AMP-activated protein kinase (AMPK) which functions as both a cellular fuel gauge and co-ordinator of whole-body metabolism. Our goal is to improve AMPK drug potency by identifying novel processes that sensitize AMPK to drugs.
Placental nutrient transport shows how complex traits evolve. This project aims to use amino acid transport in the vertebrate placenta as a model to demonstrate how genes are recruited and modified to produce a major organ. Using an innovative combination of a new technology, selected reaction monitoring, and transcriptomic and molecular approaches, plus carefully selected Australian species pairs, this project will study the evolution of a complex trait (placental amino acid transport). The pr ....Placental nutrient transport shows how complex traits evolve. This project aims to use amino acid transport in the vertebrate placenta as a model to demonstrate how genes are recruited and modified to produce a major organ. Using an innovative combination of a new technology, selected reaction monitoring, and transcriptomic and molecular approaches, plus carefully selected Australian species pairs, this project will study the evolution of a complex trait (placental amino acid transport). The project will provide fundamental advances in our knowledge of the nutrient transport during pregnancy that is required to produce a healthy baby.Read moreRead less
Role Of IGF Binding Protein-3 (IGFBP-3) And IGFBP-5 As Modulators Of Nuclear Hormone Signalling
Funder
National Health and Medical Research Council
Funding Amount
$465,750.00
Summary
The insulin-like growth factors are small proteins involved in the growth of most tissues. Their actions are regulated by binding to larger proteins (known as IGFBPs) in the bloodstream and outside the cell. However, some IGFBPs are also found inside cells, where they seem to carry out other functions. We believe that two of these binding proteins, IGFBP-3 and IGFBP-5, change the way cells respond to vitamin A and vitamin D. These two vitamins are important in cell growth and in the way certain ....The insulin-like growth factors are small proteins involved in the growth of most tissues. Their actions are regulated by binding to larger proteins (known as IGFBPs) in the bloodstream and outside the cell. However, some IGFBPs are also found inside cells, where they seem to carry out other functions. We believe that two of these binding proteins, IGFBP-3 and IGFBP-5, change the way cells respond to vitamin A and vitamin D. These two vitamins are important in cell growth and in the way certain cells perform specialised functions. In test-tube experiments, IGFBP-3 and IGFBP-5 interact directly with the receptors that regulate the effects of these hormones. If the same thing happens inside the cell, IGFBP-3 and IGFBP-5 could change the way these receptors respond to signals from outside the cell. We will investigate what effect these IGFBPs have in living cells and in whole animals and how this may relate to human disease. If we are able to understand how IGFBP-3 and IGFBP-5 affect the way cells respond to vitamin A and D, then we may be able to develop new ways to treat certain human diseases.Read moreRead less
Structural And Functional Analysis Of A Cancer-linked Co-regulator Complex
Funder
National Health and Medical Research Council
Funding Amount
$729,571.00
Summary
We seek to understand the mechanisms by which genes are switched on and off throughout our lifetime. A number of multi-component protein machines are involved in this process but their make-up and mechanism of action is not understood. We will investigate the structure and function of one of these machines that has been strongly linked to cancer.
Molecular Regulation Of Metabolism And Body Composition By Ski Via Crosstalk With Nuclear Hormone Receptor Signalling.
Funder
National Health and Medical Research Council
Funding Amount
$558,441.00
Summary
Obesity is a common and burdensome health problem in the community which leads to diabetes and heart disease. A number of factors, including hormones play important roles in determing risk of obesity. This study proposes to investigate whether the Ski gene which is a regulatory factor for many hormones affects metabolism in transgenic mouse models of altered Ski function. The proposed studies may identify Ski as a target for therapy for obesity and improvement in sketal muscle metabolism.
Discovery Early Career Researcher Award - Grant ID: DE160100755
Funder
Australian Research Council
Funding Amount
$371,000.00
Summary
Evolution of genome architecture. The project aims to understand how changes to genome architecture over evolutionary time are linked to the diversity of animal morphology. Our genome sequence is arranged into higher order structures that enable coordinated gene expression. The appropriate expression of genes in time and space is necessary to produce the multitude of cell types that make up a multicellular organism. Yet, to date, genome topology is poorly explored, especially between species. Th ....Evolution of genome architecture. The project aims to understand how changes to genome architecture over evolutionary time are linked to the diversity of animal morphology. Our genome sequence is arranged into higher order structures that enable coordinated gene expression. The appropriate expression of genes in time and space is necessary to produce the multitude of cell types that make up a multicellular organism. Yet, to date, genome topology is poorly explored, especially between species. The project involves comparisons of the 3D structure of genomes in divergent species. These findings are expected to inform the underlying principles of gene regulation in animals and species evolution.Read moreRead less
A molecular/morphological view of animal evolution based on marsupials. This project aims to provide high-accuracy methods of evolutionary inference extendable to nearly all other organisms. It aims to research the evolution of animal diversity and calibrate evolutionary timescales on a case study of marsupial mammals, and differentiate between internal and external factors that govern animals’ ability to adapt and diversify. The project will collate a large, open-source three-dimensional catalo ....A molecular/morphological view of animal evolution based on marsupials. This project aims to provide high-accuracy methods of evolutionary inference extendable to nearly all other organisms. It aims to research the evolution of animal diversity and calibrate evolutionary timescales on a case study of marsupial mammals, and differentiate between internal and external factors that govern animals’ ability to adapt and diversify. The project will collate a large, open-source three-dimensional catalogue of the evolving marsupial skeleton, which could provide a detailed and publicly accessible narrative of the evolutionary past and future adaptability of Australian marsupials. The proposed development of methods to quantify the effect of past and present biodiversity crises (e.g. environmental change) is expected to inform longer-term conservation planning.Read moreRead less
Predicting the movement speeds of animals. The project seeks to reveal how marsupials modify their movement patterns and speeds as they navigate risky environments, and show how movement contributes to vulnerability and resilience. Movement is central to animal behaviour and the survival of species, because it underlies feeding, mating and the ability to escape from predators. However, we lack a framework for predicting how fast animals should move through their habitats given their needs to con ....Predicting the movement speeds of animals. The project seeks to reveal how marsupials modify their movement patterns and speeds as they navigate risky environments, and show how movement contributes to vulnerability and resilience. Movement is central to animal behaviour and the survival of species, because it underlies feeding, mating and the ability to escape from predators. However, we lack a framework for predicting how fast animals should move through their habitats given their needs to conserve energy, avoid detection by predators and minimise risks of injury or death. This project aims to develop mathematical models to predict how fast animals should move and then test these predictions using native species of conservation concern. This is expected to extend the field of performance ecology as well as inform management strategies for vulnerable marsupials.Read moreRead less
Can muscles tune foot stiffness to enhance efficiency of human locomotion? This project aims to understand the key role that muscles might play in supporting the arch of the foot and determine if this improves the efficiency of human walking and running. The human foot is known to act like a spring to store and return energy during walking and running. The project hypothesises that this function is enhanced by muscular contributions within the foot that act to tune the stiffness of the foot and ....Can muscles tune foot stiffness to enhance efficiency of human locomotion? This project aims to understand the key role that muscles might play in supporting the arch of the foot and determine if this improves the efficiency of human walking and running. The human foot is known to act like a spring to store and return energy during walking and running. The project hypothesises that this function is enhanced by muscular contributions within the foot that act to tune the stiffness of the foot and maximise efficiency of force production. Exploration of how foot stiffness is controlled during human movement is expected to improve our understanding of the evolution of human walking and running and contribute to improving the design of modern footwear.Read moreRead less