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.
Why Is The Bone Marrow A “hot-spot” For Myeloma Plasma Cell Metastasis: Are There Gremlins In The System?
Funder
National Health and Medical Research Council
Funding Amount
$651,979.00
Summary
Most cancer patients die because their cancer spreads from a primary site to other tissues in the body. Once escaping the primary site, 70% of all tumours will spread to bone. This raises the question, why is bone a preferred destination for cancer cells? We provide evidence that Gremlin1, made by non-cancer cells within bone, is a key protein that supports cancer growth. This study will examine whether inhibiting Gremlin1 is a potential therapy to inhibit cancer spreading to bone.
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.
Co-ordinated Action of ATM and DNA-PK in DNA damage recognition. The aim of this project is to investigate the mechanism of repair of double straind breaks in DNA sustained after radiation damage. Specifically we will focus on two proteins ATM (mutated in the genetic disorder ataxia-telangiectasia) and DNA-PK mutated in scid mice. There two proteins recognize double straind breaks in DNA and signal this damage to the DNA repair machinery of the cell and to cell cycle checkpoints. The emphasis ....Co-ordinated Action of ATM and DNA-PK in DNA damage recognition. The aim of this project is to investigate the mechanism of repair of double straind breaks in DNA sustained after radiation damage. Specifically we will focus on two proteins ATM (mutated in the genetic disorder ataxia-telangiectasia) and DNA-PK mutated in scid mice. There two proteins recognize double straind breaks in DNA and signal this damage to the DNA repair machinery of the cell and to cell cycle checkpoints. The emphasis here will be in the relationship between the two proteins in co-ordinating the repair of breaks in DNA. This information will be important in understanding mechanisms for maintaining the integrity of the genome.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.
Hearing, social connectedness, and well-being of ageing adults in Australia. Hearing ability declines with age and hearing loss has a fundamental impact on an adult’s ability to communicate and, in turn, socially connect with others. This benchmark study aims to apply innovative, quantitative and qualitative methods to examine the real-world social connections of adults with hearing loss who use or do not use hearing aids. This project expects to increase understanding of the social impacts of a ....Hearing, social connectedness, and well-being of ageing adults in Australia. Hearing ability declines with age and hearing loss has a fundamental impact on an adult’s ability to communicate and, in turn, socially connect with others. This benchmark study aims to apply innovative, quantitative and qualitative methods to examine the real-world social connections of adults with hearing loss who use or do not use hearing aids. This project expects to increase understanding of the social impacts of age-related hearing loss and the relationship to hearing rehabilitation. The expected outcomes have the potential to guide research, policy, and practice for ageing Australians. This should provide significant benefits, such as reducing social isolation and enhancing the well-being of millions of Australians.Read moreRead less
Identifying Novel Long-noncoding RNAs Involved In The Development Of Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$785,204.00
Summary
Recent studies have identified regions within the human genome in which DNA sequence variations are associated with an increased risk of breast cancer. The aim of this proposal is to identify and characterise these non-coding genes that are modulate breast cancer risk. Understanding how sequences variations that alter these novel genes contribute to breast cancer will provide novel avenues for therapy.
Organisation, expression and diversity of the sub-telomeric regions of the ancient eukaryote, Giardia duodenalis. We propose to extend our findings on the extreme plasticity of the structure and organisation of the sub-telomeric region of the complete genome of Giardia by more extensive chromosome walking, and comparison of different isolates. These regions are subject to gene conversion, transcriptional silencing, gene mobility, recombination, variable surface protein expression, subtelomeric i ....Organisation, expression and diversity of the sub-telomeric regions of the ancient eukaryote, Giardia duodenalis. We propose to extend our findings on the extreme plasticity of the structure and organisation of the sub-telomeric region of the complete genome of Giardia by more extensive chromosome walking, and comparison of different isolates. These regions are subject to gene conversion, transcriptional silencing, gene mobility, recombination, variable surface protein expression, subtelomeric instability and the insertion of transposable elements, a dynamic balance between structural conservation and rapid evolution. This is a rare opportunity to understand the forces at work in moulding eukaryotic sub-telomeric sequences because Giardia is not constrained by sexual homogenisation and the dynamic variability is retained.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