Nuclear alarmins escalate tissue immune responses. Humans and other animals are constantly exposed to potential threats, including microbes on and near the body. Animals can live with such dangers because these everyday encounters are made harmless by the immune system. It is unclear how cells distinguish low-danger threats from high-danger threats. This proposal seeks to reveal how immune cells identify increasing levels of threat and appropriately escalate their responses. Expected outcomes in ....Nuclear alarmins escalate tissue immune responses. Humans and other animals are constantly exposed to potential threats, including microbes on and near the body. Animals can live with such dangers because these everyday encounters are made harmless by the immune system. It is unclear how cells distinguish low-danger threats from high-danger threats. This proposal seeks to reveal how immune cells identify increasing levels of threat and appropriately escalate their responses. Expected outcomes include new insights into how immune cells and tissues respond according to the posing threat. Project benefits include understanding how to manipulate danger responses for future basic research and commercial applications, and fundamental understanding of how animals flourish in a dangerous world.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
The core inflammasome as a model for caspase activation. This project aims to change the paradigm for the structure of the active inflammasome. Inflammasomes activate caspases, enzymes central to cell death and inflammatory processes. The current concept of inflammasomes is that caspases are recruited into a single massive protein complex seen as a “speck” in the cell. This project proposes the speck is a terminal stage, after the major enzymatic activity is over. This project aims to purify sma ....The core inflammasome as a model for caspase activation. This project aims to change the paradigm for the structure of the active inflammasome. Inflammasomes activate caspases, enzymes central to cell death and inflammatory processes. The current concept of inflammasomes is that caspases are recruited into a single massive protein complex seen as a “speck” in the cell. This project proposes the speck is a terminal stage, after the major enzymatic activity is over. This project aims to purify smaller early stage inflammasome complexes, for structural analysis. The outcome will be a clearer understanding of processes of caspase activation and inflammasome formation. This will provide significant benefits, such as improve our understanding of processes of cell death and innate immunity, and train students.Read moreRead less
Regulation of cell proliferation and survival by the ubiquitin system. This project aims to investigate how the fundamental processes of cell division and cell death are controlled at the molecular level by protein degradation enzymes (known as ubiquitin ligases), and how these regulate cellular homeostasis. Using interdisciplinary approaches incorporating proteomics, biochemistry, and molecular cell biology, this project seeks to delineate the components of signalling pathways implicated in the ....Regulation of cell proliferation and survival by the ubiquitin system. This project aims to investigate how the fundamental processes of cell division and cell death are controlled at the molecular level by protein degradation enzymes (known as ubiquitin ligases), and how these regulate cellular homeostasis. Using interdisciplinary approaches incorporating proteomics, biochemistry, and molecular cell biology, this project seeks to delineate the components of signalling pathways implicated in the degradation of proteins implicated in cell division and cell death. Expected outcomes include an increased understanding of how proteins are specifically selected for degradation. Protein degradation pathways operate with remarkable selectivity and this work is expected to illuminate the mechanisms of substrate targeting. The biochemical approaches will provide insight and impact in the areas of cell signaling, organelle biology and cell biology.Read moreRead less
Regulation of autophagy dependent cell and tissue deletion. This project aims to elucidate novel mechanisms that regulate autophagy-depdendent cell death during animal development. It will combine the power of Drosophila genetics with multidisciplinary approaches, such as proteomics, bioinformatics and cell biology. Given the conserved nature of autophagy the oucomes will provide highly topical and exciting new knowledge of broad biological significance. The project will help establishing inter ....Regulation of autophagy dependent cell and tissue deletion. This project aims to elucidate novel mechanisms that regulate autophagy-depdendent cell death during animal development. It will combine the power of Drosophila genetics with multidisciplinary approaches, such as proteomics, bioinformatics and cell biology. Given the conserved nature of autophagy the oucomes will provide highly topical and exciting new knowledge of broad biological significance. The project will help establishing international collaborations, enhancing Australia’s competitiveness and reputation in an important area of research, and provide training of HDR students in skills across a range of areas. In the long-term the research findings may translate into improved agriculture, food production and human health outcomes.Read moreRead less
Genetic control of tissue growth in animals. This project aims to understand how the animal body grows. This project expects to generate new knowledge and understanding of the genetic programs that govern the size and shape of animal tissues, through use of cutting-edge genome editing approaches in laboratory animals. Expected outcomes of this project include the production of genetically engineered animals with altered tissue growth, development of new theories for how tissue growth is normal ....Genetic control of tissue growth in animals. This project aims to understand how the animal body grows. This project expects to generate new knowledge and understanding of the genetic programs that govern the size and shape of animal tissues, through use of cutting-edge genome editing approaches in laboratory animals. Expected outcomes of this project include the production of genetically engineered animals with altered tissue growth, development of new theories for how tissue growth is normally controlled and how it can be manipulated industrially. This should provide significant benefits, impacting stem cell biology (improving stem cell production), tissue engineering (improving growth of artificial tissues), veterinary science and agriculture (improving productivity).Read moreRead less
Decoding the spatiotemporal control of DNA replication and repair. DNA replication is the fundamental mechanism of genetic inheritance and essential for all cellular life. This project aims to inform our understanding of how human cells coordinate the DNA replication machinery in time and space to accurately copy the human genome. By applying multiple innovative approaches and employing an interdisciplinary research team, this project is anticipated to generate new knowledge that explains how th ....Decoding the spatiotemporal control of DNA replication and repair. DNA replication is the fundamental mechanism of genetic inheritance and essential for all cellular life. This project aims to inform our understanding of how human cells coordinate the DNA replication machinery in time and space to accurately copy the human genome. By applying multiple innovative approaches and employing an interdisciplinary research team, this project is anticipated to generate new knowledge that explains how the human genome is replicated. This knowledge is expected to generate research publications of high quality and provide economic benefits, such as unlocking new potentially patentable DNA technologies. Read moreRead less
Programmed cell death signalling in innate immunity. This proposal aims to address the under-explored potential for programmed cell death to promote innate immune cell signalling, which is a critical and fundamental biological process. It aims to generate new knowledge in the areas of cell death and innate signalling using innovative interdisciplinary approaches and discover new molecules that impact innate inflammatory responses. The expected outcomes of this project are to enhance our basic un ....Programmed cell death signalling in innate immunity. This proposal aims to address the under-explored potential for programmed cell death to promote innate immune cell signalling, which is a critical and fundamental biological process. It aims to generate new knowledge in the areas of cell death and innate signalling using innovative interdisciplinary approaches and discover new molecules that impact innate inflammatory responses. The expected outcomes of this project are to enhance our basic understanding of cell death, and build interdisciplinary collaborations. This work should provide significant benefit to the economy and health of Australians, as it is expected to identify molecules that will be of interest to the pharmaceutical and biotechnology industries.Read moreRead less