Discovery Early Career Researcher Award - Grant ID: DE240101286
Funder
Australian Research Council
Funding Amount
$469,707.00
Summary
SARS-CoV-2-induced dead cell fragments drive viral uptake and inflammation. This project will apply advanced cell biology and imaging techniques to investigate how macrophages, which lacks a canonical receptor for viral entry, become infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and elicit inflammatory responses. Its insights into a novel pathway of viral entry is expected to advance our understanding of host-pathogen interaction. The project is intended to uncover t ....SARS-CoV-2-induced dead cell fragments drive viral uptake and inflammation. This project will apply advanced cell biology and imaging techniques to investigate how macrophages, which lacks a canonical receptor for viral entry, become infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and elicit inflammatory responses. Its insights into a novel pathway of viral entry is expected to advance our understanding of host-pathogen interaction. The project is intended to uncover the role of SARS-CoV-2-induced dead cell fragmentation in promoting viral uptake and inflammation. Its findings should provide significant scientific, health and economic benefits by informing new research directions on infection and innate immunity as well as future therapeutic designs for infection treatment.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE120100794
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Revealing dynamic mechanisms controlling pluripotency in mammalian stem cells and embryos. Every cell of our mature bodies originates from 'pluripotent' cells present in the early mammalian embryo. These cells can be captured and grown in plastic dishes. The project will use imaging methods to reveal how gene regulatory molecules control pluripotent cells in the embryo and in culture.
Discovery Early Career Researcher Award - Grant ID: DE220100259
Funder
Australian Research Council
Funding Amount
$467,964.00
Summary
Interrogating the adaptive potential of skeletal muscle. Disruptions to muscle oxidative capacity and growth signalling underpin atrophy and dysfunction with ageing, which impacts on an individual’s quality of life. These biological processes are thought to be mutually exclusive and compete during muscle adaptation. This project aims to define how these processes regulate the extent of muscle adaptation, and how modifying these attributes influence functional capacity in the context of ageing. T ....Interrogating the adaptive potential of skeletal muscle. Disruptions to muscle oxidative capacity and growth signalling underpin atrophy and dysfunction with ageing, which impacts on an individual’s quality of life. These biological processes are thought to be mutually exclusive and compete during muscle adaptation. This project aims to define how these processes regulate the extent of muscle adaptation, and how modifying these attributes influence functional capacity in the context of ageing. This project will provide fundamental new knowledge in understanding how modifying muscle attributes influence successful ageing. This knowledge will improve resilience, productivity, and wellbeing of all Australians, with implications for reducing societal and economic burden.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE170100239
Funder
Australian Research Council
Funding Amount
$372,000.00
Summary
The molecular basis of endothelial mechanotransduction through TRPV4. This project aims to understand how blood flow dynamics coordinate the plasma membrane localisation and interaction of the transient receptor potential vanilloid 4 (TRPV4), a candidate mechanosensitive ion channel broadly expressed in endothelium with physiological and pathological roles in the cardiovascular system, with other mechanoreceptors and the physiological relevance of these events. Blood flow haemodynamics affect ca ....The molecular basis of endothelial mechanotransduction through TRPV4. This project aims to understand how blood flow dynamics coordinate the plasma membrane localisation and interaction of the transient receptor potential vanilloid 4 (TRPV4), a candidate mechanosensitive ion channel broadly expressed in endothelium with physiological and pathological roles in the cardiovascular system, with other mechanoreceptors and the physiological relevance of these events. Blood flow haemodynamics affect cardiovascular health and morphogenesis. This project will highlight the role of TRPV4 channels in the short- and long-term adaptive responses to shear stress and will also have significant potential for application in future drug discovery.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE140100500
Funder
Australian Research Council
Funding Amount
$383,066.00
Summary
Unravelling the holistic genetic control of vertebrate development. Understanding the genetic regulation of embryo formation is the cornerstone of developmental biology. As four per cent of Australian children are born with some form of prenatal defect, understanding the basic biology of embryogenesis is paramount for long-range development of future therapies. We have identified a highly conserved transcription factor, Grhl3, which regulates multiple stages of embryonic formation. Using advance ....Unravelling the holistic genetic control of vertebrate development. Understanding the genetic regulation of embryo formation is the cornerstone of developmental biology. As four per cent of Australian children are born with some form of prenatal defect, understanding the basic biology of embryogenesis is paramount for long-range development of future therapies. We have identified a highly conserved transcription factor, Grhl3, which regulates multiple stages of embryonic formation. Using advanced genetic models, this project will characterise the role of Grhl3 in the regulation of cellular migration and craniofacial skeleton and brain development. The project will also identify the target genes which Grhl3 regulates. The identification of such transcriptional networks is imperative to understanding the holistic molecular control of embryogenesis.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE230101681
Funder
Australian Research Council
Funding Amount
$457,139.00
Summary
Cryo-electron microscopy determination of G protein-coupled receptor states. This project aims to address fundamental knowledge gaps in understanding of the molecular mechanisms of peptide hormone G protein-coupled receptor activation. This will be achieved through cryo-electron microscopy determination of the structure and dynamics of key intermediate states in activation. Novel biochemical approaches will be applied to capture these states, using as exemplar the glucagon receptor that has a br ....Cryo-electron microscopy determination of G protein-coupled receptor states. This project aims to address fundamental knowledge gaps in understanding of the molecular mechanisms of peptide hormone G protein-coupled receptor activation. This will be achieved through cryo-electron microscopy determination of the structure and dynamics of key intermediate states in activation. Novel biochemical approaches will be applied to capture these states, using as exemplar the glucagon receptor that has a broad range of pharmacological tools to facilitate isolation of distinct functional states. The knowledge gained from these studies will advance fundamental understanding of physiologically important receptor activation and efficacy, while the approaches developed will enable similar investigation of other receptor classes.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE150101777
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Understanding the role of exosomes in intercellular communication. Exosomes, small packages released by cells, are powerful signalling organelles that can activate neighbouring cells by transferring proteins and RNA. Currently, it is unknown whether exosomes have similar membrane protein/lipid composition to that of the host cell. This project aims to explore the similarities and differences between the exosomal and host cell membranes in terms of the protein/lipid composition. In addition, the ....Understanding the role of exosomes in intercellular communication. Exosomes, small packages released by cells, are powerful signalling organelles that can activate neighbouring cells by transferring proteins and RNA. Currently, it is unknown whether exosomes have similar membrane protein/lipid composition to that of the host cell. This project aims to explore the similarities and differences between the exosomal and host cell membranes in terms of the protein/lipid composition. In addition, the project aims to study how the proteins and RNA are packaged into exosomes. Membrane molecules that are detected only in the exosomes may have important signalling implications and may aid in the uptake/fusion of exosomes by/with target cells. The project aims to improve our understanding on signalling mediated by exosomes.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE180101165
Funder
Australian Research Council
Funding Amount
$365,058.00
Summary
Structural insights into adenosine receptors. This project aims to investigate mechanisms underlying ligand binding and signal transduction at G protein-coupled receptors (GPCRs) by utilising the adenosine receptor family as a model system. This interdisciplinary project will use structural biology, pharmacology and biochemistry. The expected outcomes include understanding ligand selectivity across the four adenosine receptor family members. This should provide significant benefits, such as adva ....Structural insights into adenosine receptors. This project aims to investigate mechanisms underlying ligand binding and signal transduction at G protein-coupled receptors (GPCRs) by utilising the adenosine receptor family as a model system. This interdisciplinary project will use structural biology, pharmacology and biochemistry. The expected outcomes include understanding ligand selectivity across the four adenosine receptor family members. This should provide significant benefits, such as advancement of fundamental knowledge that could also lead to therapeutic development.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE200100611
Funder
Australian Research Council
Funding Amount
$427,116.00
Summary
How do extracellular vesicles fuse with cells to deliver messages? Aims: This project aims to investigate how tiny packages released by all cells in the human body, called extracellular vesicles, deliver messages into neighbouring cells facilitating cell-to-cell communication.
Significance: This project expects to generate key knowledge in the area of cell-to-cell communication by using innovative molecular biology approaches and cutting-edge microscopy and biophysical techniques.
Expected outco ....How do extracellular vesicles fuse with cells to deliver messages? Aims: This project aims to investigate how tiny packages released by all cells in the human body, called extracellular vesicles, deliver messages into neighbouring cells facilitating cell-to-cell communication.
Significance: This project expects to generate key knowledge in the area of cell-to-cell communication by using innovative molecular biology approaches and cutting-edge microscopy and biophysical techniques.
Expected outcomes: Expected outcomes include high resolution details of which molecules are packaged onto extracellular vesicles and how they are delivered into recipient cells.
Benefits: This project should contribute significantly to understanding extracellular vesicle function and guide their eventual use as therapeutics.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE170100152
Funder
Australian Research Council
Funding Amount
$372,000.00
Summary
Molecular insight into allosteric modulation of G protein-coupled receptors. The project aims to understand the molecular mechanisms underlying signal transduction and allosteric modulation of G protein-coupled receptors (GPCRs). Allosteric modulation of proteins is a fundamental process where two distinctly different binding sites are linked through a conformational change. This project will use structural biology, medicinal chemistry and analytical pharmacology to investigate how chemical prob ....Molecular insight into allosteric modulation of G protein-coupled receptors. The project aims to understand the molecular mechanisms underlying signal transduction and allosteric modulation of G protein-coupled receptors (GPCRs). Allosteric modulation of proteins is a fundamental process where two distinctly different binding sites are linked through a conformational change. This project will use structural biology, medicinal chemistry and analytical pharmacology to investigate how chemical probes modulate GPCRs at an atomic level, and understand the mechanisms underlying signal transduction. Project outcomes are intended to advance membrane protein crystallography and GPCR biology, and benefit the pharmaceutical industry.Read moreRead less