The regulation of skeletal muscle mass. This project aims to delineate a pathway involved in regulating skeletal muscle mass, and examine whether disrupting mitochondrial phospholipid synthesis affects mitochondrial structure and function, causing muscle wasting. Defining a new atrophy pathway will advance understanding of the mechanisms that control muscle mass. This project could have important economic and quality of life benefits, especially for agriculture, where achieving optimal muscle ma ....The regulation of skeletal muscle mass. This project aims to delineate a pathway involved in regulating skeletal muscle mass, and examine whether disrupting mitochondrial phospholipid synthesis affects mitochondrial structure and function, causing muscle wasting. Defining a new atrophy pathway will advance understanding of the mechanisms that control muscle mass. This project could have important economic and quality of life benefits, especially for agriculture, where achieving optimal muscle mass ensures international competitiveness, productivity and economic growth, and successful ageing, where maintaining muscle mass is essential.Read moreRead less
Regulator Of G-protein Signalling-5: A Key Modulator Of Vascular Maturation And The
Funder
National Health and Medical Research Council
Funding Amount
$548,396.00
Summary
Tumours progressively grow in part because they escape destruction by the immune system. New blood vessels grow inside tumours by a process called angiogenesis, which in turn stops disease-fighting cells in their tracks. However, we have now discovered that it is possible to reverse angiogenesis by normalising the blood vessels. This effectively means the barriers are broken down and the tumour can be opened to the immune system or cancer fighting drugs. Furthermore, we have identified a protein ....Tumours progressively grow in part because they escape destruction by the immune system. New blood vessels grow inside tumours by a process called angiogenesis, which in turn stops disease-fighting cells in their tracks. However, we have now discovered that it is possible to reverse angiogenesis by normalising the blood vessels. This effectively means the barriers are broken down and the tumour can be opened to the immune system or cancer fighting drugs. Furthermore, we have identified a protein which appears to be very important for normalisation, a process which is currently not well understood. This proposal continues our pioneering work on vessel normalisation and will use models of highest clinical relevance to study the dynamics of vessel remodelling in tumours. Our approach is different to current angiogenesis research which simply tries to block or destroy the blood vessels that feed tumours. We expect our findings to lead to highly specific and effective anti-tumour therapies. Moreover, vessel growth in tumours has striking parallels to other vascular processes in the body, which have important implications for major and common human diseases such as high blood pressure and atherosclerosis. We now have the tools to study these processes and their abnormalities in our newly established disease model. By gaining insight into these disorders we will be able to develop novel approaches to stop disease progression.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE120101242
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Regulation of germ cell number and quality by Fizzy-related protein. Females have a limited supply of eggs in their ovaries and it appears that the Fizzy-related gene (FZR1) is important in making sure this full complement is gained. By using novel mouse knockouts of the FZR1 gene, the project will determine how this protein functions at the earliest stages of egg development.
Investigation of the biochemical and physiological functions of the negative regulator of cytokine signalling SOCS-2. Cytokines exert their effects by binding and signalling through specific cell surface receptors to elicit their biological action, and if left unchecked, this signalling can cause significant tissue damage and toxicity. Our aim is to characterise a novel regulator of cytokine signalling, SOCS-2. SOCS-2 is strongly implicated in the regulation of post-natal growth as SOCS-2 defici ....Investigation of the biochemical and physiological functions of the negative regulator of cytokine signalling SOCS-2. Cytokines exert their effects by binding and signalling through specific cell surface receptors to elicit their biological action, and if left unchecked, this signalling can cause significant tissue damage and toxicity. Our aim is to characterise a novel regulator of cytokine signalling, SOCS-2. SOCS-2 is strongly implicated in the regulation of post-natal growth as SOCS-2 deficient animals are 40 percent larger than normal. Consequently, we wish to determine how SOCS-2 acts to limit the size of an animal and whether this involves regulation of growth hormone action.Read moreRead less
Molecular control of embryonic diapause. Many species can halt growth of the early embryo (diapause). This project will use novel animal models and new proteomics techniques to clarify what signals from the uterus control diapause of the embryo. This may uncover new mechanisms for cell regulation that will be relevant to the biology of stem cells, cancer and reproductive technologies.
Discovery Early Career Researcher Award - Grant ID: DE180100859
Funder
Australian Research Council
Funding Amount
$365,058.00
Summary
Phosphatidylserine: a regulator of muscle and mitochondrial biology? This project aims to characterise a novel pathway involved in regulating skeletal muscle mass through effects on mitochondrial function. This project will examine how degradation causes mitochondrial abnormalities leading to severe muscle wasting. This project is expected to advance understanding of how pathways interact, thus identifying novel mechanisms that impact on muscle structure and function. Understanding what makes mu ....Phosphatidylserine: a regulator of muscle and mitochondrial biology? This project aims to characterise a novel pathway involved in regulating skeletal muscle mass through effects on mitochondrial function. This project will examine how degradation causes mitochondrial abnormalities leading to severe muscle wasting. This project is expected to advance understanding of how pathways interact, thus identifying novel mechanisms that impact on muscle structure and function. Understanding what makes muscle vulnerable to atrophy is fundamental to developing strategies to counteract muscle wasting conditions. Methodologies developed will have broad application in the field of life sciences research.Read moreRead less
Revealing the mechanobiology of neural tube formation. This project aims to understand the formation of the neural tube; a fundamental tissue structure that generates the brain and the spinal cord. Using interdisciplinary approaches and exploiting recent advances in transgenic and imaging technologies, we expect to reveal the complex interplay between cells and their environment that generates mechanical forces to direct neural tissue formation. Outcomes include knowledge of previously intractab ....Revealing the mechanobiology of neural tube formation. This project aims to understand the formation of the neural tube; a fundamental tissue structure that generates the brain and the spinal cord. Using interdisciplinary approaches and exploiting recent advances in transgenic and imaging technologies, we expect to reveal the complex interplay between cells and their environment that generates mechanical forces to direct neural tissue formation. Outcomes include knowledge of previously intractable developmental processes, training of future scientists and development of international collaborations. This should provide enhanced imaging capacity, a higher quality scientific workforce and position Australia at the forefront of cell and developmental biology.Read moreRead less
Reverse chemical proteomics: harnessing yeast display for drug discovery. This project aims to develop a technique that can rapidly identify the cellular protein targets of biologically active natural products. This project expects to provide fundamental biological and chemical insights into Australia's unique biodiversity that will facilitate the development of new therapeutic agents and agrochemicals based on leads provided by Nature. Expected outcomes of this project include an optimised and ....Reverse chemical proteomics: harnessing yeast display for drug discovery. This project aims to develop a technique that can rapidly identify the cellular protein targets of biologically active natural products. This project expects to provide fundamental biological and chemical insights into Australia's unique biodiversity that will facilitate the development of new therapeutic agents and agrochemicals based on leads provided by Nature. Expected outcomes of this project include an optimised and validated platform technology for accelerating drug discovery and development. This should substantially reduce the costs associated with fighting human and animal diseases, leading to improved health, productivity and quality of life.Read moreRead less
Engineering electrochemical protein biosensors. This project plans to develop novel, sensitive, inexpensive and flexible electric biosensors to monitor potentially any molecule. It plans to use synthetic biology principles to develop a new class of artificial protein receptors that generate electric current upon encountering a molecular target. Using expertise in in vitro protein synthesis, the project plans to integrate biosensor design and electrode prototyping to achieve rapid development of ....Engineering electrochemical protein biosensors. This project plans to develop novel, sensitive, inexpensive and flexible electric biosensors to monitor potentially any molecule. It plans to use synthetic biology principles to develop a new class of artificial protein receptors that generate electric current upon encountering a molecular target. Using expertise in in vitro protein synthesis, the project plans to integrate biosensor design and electrode prototyping to achieve rapid development of low-cost broadly applicable sensory electrodes. To increase the sensitivity of the resulting sensing systems, the electrochemical receptors will be integrated with signal amplification cascades based on artificial autoinhibited proteases. The project aims to address the need for new technologies that enable collection of biological information outside of the laboratory environment.Read moreRead less
Central Muscarinic Receptors as Novel Drug Targets for Parkinson's Disease and Schizophrenia. Psychiatric and neurodegenerative disorders such as schizophrenia and Parkinson's disease are linked to alterations in the activity of neurons in the brain containing the chemical dopamine. Other types of brain neurons containing the chemical acetylcholine regulate dopamine neuron activity by acting on acetylcholine receptors located on dopamine neurons. We aim to determine how these important recepto ....Central Muscarinic Receptors as Novel Drug Targets for Parkinson's Disease and Schizophrenia. Psychiatric and neurodegenerative disorders such as schizophrenia and Parkinson's disease are linked to alterations in the activity of neurons in the brain containing the chemical dopamine. Other types of brain neurons containing the chemical acetylcholine regulate dopamine neuron activity by acting on acetylcholine receptors located on dopamine neurons. We aim to determine how these important receptors regulate dopamine neuron activity using genetically modified mice deficient in acetylcholine receptors, together with newly developed physiological methods and new acetylcholine receptor drugs. These studies will foster the design of novel acetylcholine receptor drugs as effective pharmaceutical treatments of neurological and psychiatric disorders related to brain dopamine dysfunction.Read moreRead less