How cell shape regulators control cell competition in tissue development. This project aims to determine how cell shape (polarity) regulators affect cell survival in an epithelial tissue. When mutation or wounding perturb cell shape regulators in a tissue cell, signalling pathways are altered that kill the aberrant cells. A surveillance mechanism termed "cell competition" is important to remove the damaged cells. This project will investigate a potential regulator of cell competition, the tyrosi ....How cell shape regulators control cell competition in tissue development. This project aims to determine how cell shape (polarity) regulators affect cell survival in an epithelial tissue. When mutation or wounding perturb cell shape regulators in a tissue cell, signalling pathways are altered that kill the aberrant cells. A surveillance mechanism termed "cell competition" is important to remove the damaged cells. This project will investigate a potential regulator of cell competition, the tyrosine phosphatase PTP61F, in response to perturbation of cell shape regulators, using the vinegar fly, Drosophila, and mammalian systems. This study is expected to reveal biomarkers that can be used to improve organismal fitness to increase productivity or to decrease it for pest control.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE210100604
Funder
Australian Research Council
Funding Amount
$436,600.00
Summary
How do cells sense and react to mechanical forces? There is accumulating evidence that mechanical forces exerted on tissues and cells strongly influences their behaviour. My research aims to understand how cells sense and respond to forces experienced throughout life. Using a combination of three-dimensional cell and tissue culture methods, I will investigate how compressive forces change the biochemistry of cells and their functionality. This work is aimed at generating fundamental knowledge to ....How do cells sense and react to mechanical forces? There is accumulating evidence that mechanical forces exerted on tissues and cells strongly influences their behaviour. My research aims to understand how cells sense and respond to forces experienced throughout life. Using a combination of three-dimensional cell and tissue culture methods, I will investigate how compressive forces change the biochemistry of cells and their functionality. This work is aimed at generating fundamental knowledge to improve our comprehension of how cells respond to force. The expected outcome is a greater understanding of mechanical and biochemical relationships between cells and the environment, to inform fields of tissue engineering of culture scaffolds to better mimic natural cell-tissue settings.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE140100149
Funder
Australian Research Council
Funding Amount
$300,000.00
Summary
CyTOF platform for the Advanced Cytometry Facility: overcoming fluorescence spectral barriers to truly multiparametric cytometry by mass spectrometry. Cytometry by time-of-flight mass spectrometry platform for the Advanced Cytometry Facility: overcoming fluorescence spectral barriers to truly multiparametric cytometry by mass spectrometry: This project will provide a flow cytometer capable of analysing single cells by time-of-flight mass spectrometry. Antibody labels for cell components will ena ....CyTOF platform for the Advanced Cytometry Facility: overcoming fluorescence spectral barriers to truly multiparametric cytometry by mass spectrometry. Cytometry by time-of-flight mass spectrometry platform for the Advanced Cytometry Facility: overcoming fluorescence spectral barriers to truly multiparametric cytometry by mass spectrometry: This project will provide a flow cytometer capable of analysing single cells by time-of-flight mass spectrometry. Antibody labels for cell components will enable measurement of up to 100 parameters/cell. Developing analytical and modelling algorithms like Spanning tree Progression of Density normalised Events (SPADE), this project will aim to map the relationships of various unelucidated cell lineages, via functional pathway connections. New pathways thus revealed will enable elaboration and use of novel specific molecules in perturbational analyses to confirm and further enhance the understanding of these highly intricate, basic relationships. This will provide unparalleled insight, both into early development of stem cells and mechanisms of maintenance of homeostasis in differentiated cells.Read moreRead less
Characterisation Of Two New Kinases In The Hippo Tumour Suppressor Pathway
Funder
National Health and Medical Research Council
Funding Amount
$550,602.00
Summary
The Hippo pathway is a key regulator of tissue growth. It was first discovered in vinegar flies and plays a similar role in mammals. We aim to define the mechanism by which the Gish and Fray kinases control tissue growth by regulating the Hippo pathway. These studies will be performed in flies and mammalian cell culture. Our studies will shed light on how tissue growth is controlled, and have the potential to inform the way that we treat human cancers and tissue growth disorders.
Mechanisms Of Cytokine Independence During The Development Of Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$598,163.00
Summary
Signals from growth factors such as cytokines and hormones are required for cell survival. In their absence cells activate an in-built self-destruct process. Determining how cytokines regulate cell death will provide novel targets so that unwanted cells (like cancer cells) can be triggered to die and needed cells (such as brain cells) can survive.
The role of a novel protein, interferon epsilon, in reproductive tract immunity. This project aims to develop a world-first description of a new protein that has a protective role against female reproductive tract infections. This unique protein, called interferon epsilon, was discovered in our laboratory. This project will facilitate development of new therapeutic approaches of benefit in diseases such as Chlamydia and Herpes Simplex Virus.
Using viral inhibitors to understand the regualtion of apoptosis. Apoptosis is a form of cell death that is critical for the development and well-being of multicellular organisms. The activity of Bak or Bax, two members of the Bcl-2 family, are essential for apoptosis to proceed, but how the activity of these two proteins is regulated is unclear. Many viruses encode inhibitors of apoptosis and the project will make use of two novel viral inhibitors that specifically target Bak. The project aims ....Using viral inhibitors to understand the regualtion of apoptosis. Apoptosis is a form of cell death that is critical for the development and well-being of multicellular organisms. The activity of Bak or Bax, two members of the Bcl-2 family, are essential for apoptosis to proceed, but how the activity of these two proteins is regulated is unclear. Many viruses encode inhibitors of apoptosis and the project will make use of two novel viral inhibitors that specifically target Bak. The project aims to determine how the Bak inhibitors function and to provide valuable insights into the normal mechanisms regulating Bak activity.Read moreRead less
Molecular determinants of inflammatory caspase activity upon inflammasomes. Most processes fundamental to life rely on the timely, and regulated, execution of cellular functions. The innate immune system, in which both timing and regulation is paramount, rapidly detects invading microbes and induces a measured and timely antimicrobial response to clear infection. This project aims to address a key knowledge gap by characterising a mechanism for timely and controlled immune system activation and ....Molecular determinants of inflammatory caspase activity upon inflammasomes. Most processes fundamental to life rely on the timely, and regulated, execution of cellular functions. The innate immune system, in which both timing and regulation is paramount, rapidly detects invading microbes and induces a measured and timely antimicrobial response to clear infection. This project aims to address a key knowledge gap by characterising a mechanism for timely and controlled immune system activation and immune cell death via the non-canonical inflammasome. We do not currently understand how some immune pathways are turned on or off. This project will yield fundamental insight into mechanisms of mammalian inflammasome, inflammation and anti-microbial responses.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE210100011
Funder
Australian Research Council
Funding Amount
$900,000.00
Summary
Integrated Multimodal System for Multiplexed Imaging of Signal Transduction. This project will introduce a unique microscopy platform and associated technologies into the Australian research environment that will enable researchers to redefine our understanding of molecular signal transduction. The instrumentation will enable the multidimensional imaging of live cells with unprecendented speed and sensitivity. The featured imaging modalities will enable the integration of distinct biological, ....Integrated Multimodal System for Multiplexed Imaging of Signal Transduction. This project will introduce a unique microscopy platform and associated technologies into the Australian research environment that will enable researchers to redefine our understanding of molecular signal transduction. The instrumentation will enable the multidimensional imaging of live cells with unprecendented speed and sensitivity. The featured imaging modalities will enable the integration of distinct biological, biochemical and chemical probes with a focus on minimizing phototoxicity. Expected outcomes include new fundamental knowledge on molecular signal transduction and cell heterogeneity; development of novel probes and methodologies and the development of new and existing interdisciplinary research collaborations. Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE150100066
Funder
Australian Research Council
Funding Amount
$440,000.00
Summary
Mass Cytometry: A breakthrough in multidimensional systems biology. Mass cytometry - a breakthrough in multidimensional systems biology: Mass Cytometry by Time of Flight marries the resolution, specificity and sensitivity of atomic stable isotope mass spectrometry to the high-throughput, single-cell analytical advantages of flow cytometry. Using molecular probes conjugated with stable isotope tags, a large increase is possible in the number of simultaneous quantitative measurements in complex sa ....Mass Cytometry: A breakthrough in multidimensional systems biology. Mass cytometry - a breakthrough in multidimensional systems biology: Mass Cytometry by Time of Flight marries the resolution, specificity and sensitivity of atomic stable isotope mass spectrometry to the high-throughput, single-cell analytical advantages of flow cytometry. Using molecular probes conjugated with stable isotope tags, a large increase is possible in the number of simultaneous quantitative measurements in complex samples. These parameters, denoting cell type, function and signalling status, will make possible future advances in the understanding of the diversity of cell phenotype and function with a systems biology approach. Read moreRead less