Hedgehog Signalling In Limb And Craniofacial Development And Disease
Funder
National Health and Medical Research Council
Funding Amount
$494,544.00
Summary
Anomalies of the face and limbs are amongst the most common features of human birth defects, and their frequent association suggests that the same genes are involved in governing the development of the limbs and face during embryogenesis. We have used a genomics-based approach to identify genes involved in limb development based on their alteration in a mouse model which develops extra fingers and toes. Defects in this mouse result from changes in Gli3, a gene which is known to be important in b ....Anomalies of the face and limbs are amongst the most common features of human birth defects, and their frequent association suggests that the same genes are involved in governing the development of the limbs and face during embryogenesis. We have used a genomics-based approach to identify genes involved in limb development based on their alteration in a mouse model which develops extra fingers and toes. Defects in this mouse result from changes in Gli3, a gene which is known to be important in both limb and face development. Based on the organs in which our genes of interest are active, we believe that they will also play key roles in embryonic development of the limbs, face and other organs. We now plan to investigate the regulation of a subset of these genes based on analysis in mouse models of limb and face development. In addition, we have chosen to further analyse the function of a completely novel gene we have identified which our preliminary studies suggest may play a role in the normal development of the lip and palate. These studies have the potential to shed light on the processes governing how organs develop, as well as on the molecular basis of common birth defects such as polydactyly (extra fingers and toes) and cleft palate.Read moreRead less
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.
A Fibroin-based Prosthetic Bruch's Membrane For The Treatment Of Age-related Macular Degeneration
Funder
National Health and Medical Research Council
Funding Amount
$538,080.00
Summary
Our aim is to develop a new therapy for the treatment of patients with age-related macular degeneration (AMD), a leading cause of blindness in our ageing population. The novelty of our therapy resides in using a protein derived from silk fibers (fibroin), to rebuild a healthy barrier between the outermost layer of the retina and adjacent blood vessels. We expect that the findings from this study will eventually lead to better outcomes for patients with AMD.
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.
Benefit Of 2D-strain Surveillance In Improving Cardiovascular Outcomes In Cancer Patients Undergoing Cardiotoxic Chemotherapy
Funder
National Health and Medical Research Council
Funding Amount
$2,391,979.00
Summary
Cancer survivors are susceptible to heart failure (HF) caused by heart muscle damage from chemotherapy. The current testing for this problem is based on a measure that cannot identify minor changes of cardiac function. Cardiac strain is a sensitive new marker of cardiac function which is predictive of overt dysfunction & HF. This study seeks to identify whether strain can be used to assign treatments that lead to improved cardiac function and are eventually associated with a reduction in HF.
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.
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
Discovery And Development Of Better Pain Treatments
Funder
National Health and Medical Research Council
Funding Amount
$9,613,850.00
Summary
Many forms of pain remain poorly treated, leading to significant quality of life and economic losses. This Program grant will discover and characterise new peptides from cone snails and spiders that modulate specific channels in nerves that are critical to the transmission of pain signals to the brain. Using advanced chemical and structural approaches, promising leads will be optimised for potency and stability and evaluated in disease and pathway-specific models of pain to establish their clini ....Many forms of pain remain poorly treated, leading to significant quality of life and economic losses. This Program grant will discover and characterise new peptides from cone snails and spiders that modulate specific channels in nerves that are critical to the transmission of pain signals to the brain. Using advanced chemical and structural approaches, promising leads will be optimised for potency and stability and evaluated in disease and pathway-specific models of pain to establish their clinical potential.Read moreRead less
Testing metabolic theories in ecology. There are striking similarities in the way plants and animals take up and use energy (metabolism), despite enormous variation in size and life-style. This project will make the first experimental comparison of the predictions of the two major theories for these broad patterns. The results will significantly progress this controversial and exciting field.