Evolution and specificity of alternative splicing in plants. This project aims to elucidate fundamental principles of alternative splicing, a basic mechanism that plays a vital role in several biological processes across all organisms. Plants are highly effective in adapting to varied environmental, seasonal and climatic conditions and this project aims to uncover how alternative splicing contributes to regulation of gene expression in response to developmental and environmental cues. Uncovering ....Evolution and specificity of alternative splicing in plants. This project aims to elucidate fundamental principles of alternative splicing, a basic mechanism that plays a vital role in several biological processes across all organisms. Plants are highly effective in adapting to varied environmental, seasonal and climatic conditions and this project aims to uncover how alternative splicing contributes to regulation of gene expression in response to developmental and environmental cues. Uncovering the underlying mechanisms of alternative splicing will not only advance fundamental knowledge, but also has the potential to provide tools and technologies through which sensitivities of plants to environmental stress can be potentially manipulated to benefit agriculture.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
The Role of Lck/CD8 Association in Negatively Regulating T cell Activation. This proposal aims to advance our fundamental understanding of how T cell recognition of antigens translates into a T cell activating signal. The proposal will establish whether the major T cell coreceptor also acts as a negative regulator of T cell activation in vivo when antigen recognition is unorthodox. It will also determine whether certain subsets of T cells naturally lack coreceptors in order to facilitate unortho ....The Role of Lck/CD8 Association in Negatively Regulating T cell Activation. This proposal aims to advance our fundamental understanding of how T cell recognition of antigens translates into a T cell activating signal. The proposal will establish whether the major T cell coreceptor also acts as a negative regulator of T cell activation in vivo when antigen recognition is unorthodox. It will also determine whether certain subsets of T cells naturally lack coreceptors in order to facilitate unorthodox antigen recognition. Thus, the proposal will significantly advance our understanding of, and establish new paradigms around, the regulation of T cell activation. Expected long term benefits outside the scope of this proposal include improved immunotherapies and vaccines designed to elicit or suppress T cell responses.Read moreRead less
How do cytokine receptors transmit signals? This project aims to determine the mechanisms of signal transmission by cytokine receptors using state-of-the-art microscopy techniques. Cytokines are small proteins that act as messengers between cells and play fundamental roles in biology. Cytokines bind to receptors on the surface of cells, producing a response within the cells. Yet, how the message is transmitted across the cell membrane is not well understood. Expected outcomes of this project inc ....How do cytokine receptors transmit signals? This project aims to determine the mechanisms of signal transmission by cytokine receptors using state-of-the-art microscopy techniques. Cytokines are small proteins that act as messengers between cells and play fundamental roles in biology. Cytokines bind to receptors on the surface of cells, producing a response within the cells. Yet, how the message is transmitted across the cell membrane is not well understood. Expected outcomes of this project include discovery of mechanisms general to cytokine signalling and new approaches to investigate cytokine biology. This new knowledge will benefit efforts to understand and modulate cytokine signalling in animals and humans, with future impacts in the agriculture, veterinary, and health sectors.Read moreRead less
Understanding how cells regulate self eating during starvation and stress. This project aims to investigate how autophagosomes are built during autophagy by using advanced multi-modal imaging and unique gene-edited human cell lines. This project expects to generate new knowledge on how a family of evolutionary conserved proteins regulate autophagosome formation during starvation and stress conditions. Expected outcomes include the development of frontier imaging technologies that can be subseque ....Understanding how cells regulate self eating during starvation and stress. This project aims to investigate how autophagosomes are built during autophagy by using advanced multi-modal imaging and unique gene-edited human cell lines. This project expects to generate new knowledge on how a family of evolutionary conserved proteins regulate autophagosome formation during starvation and stress conditions. Expected outcomes include the development of frontier imaging technologies that can be subsequently utilised for the advancement of any field of cell biology. This should provide significant benefits by placing Australia at the forefront of cell biology technologies and increasing our understanding of how plant and human cells can protect themselves during starvation and stress.
Read moreRead less
Australian Laureate Fellowships - Grant ID: FL180100019
Funder
Australian Research Council
Funding Amount
$2,906,976.00
Summary
An in situ structural study of Drosophila embryonic patterning. This project aims to develop and deploy an in situ structural biology approach, which enables direct visualisation of large macromolecular structures in cells, to be used in combination with molecular genetics, proteomics and computational biology. In situ structural biology has the potential to revolutionise discovery across life science, providing direct insight into macromolecular structure and function. This project will establi ....An in situ structural study of Drosophila embryonic patterning. This project aims to develop and deploy an in situ structural biology approach, which enables direct visualisation of large macromolecular structures in cells, to be used in combination with molecular genetics, proteomics and computational biology. In situ structural biology has the potential to revolutionise discovery across life science, providing direct insight into macromolecular structure and function. This project will establish the field of in situ structural biology in Australia by studying how a model organism, the fruit fly Drosophila melanogaster controls the development of how the head and tail of the embryo are specified. The project will further develop new instrumentation and approaches that will bring in situ biology to the wider scientific community.Read moreRead less
All in the family: understanding a new class of bacterial toxins. This project aims to unravel missing molecular details of how a major superfamily of proteins is able to drill holes in cell membranes. Animals, plants, fungi and bacteria all use pore-forming proteins as cell-killing weapons of mass destruction. Despite their lethal nature and their roles in infection and immunity, how these proteins work remains enigmatic. The outcomes could reveal novel mechanisms general to these proteins and ....All in the family: understanding a new class of bacterial toxins. This project aims to unravel missing molecular details of how a major superfamily of proteins is able to drill holes in cell membranes. Animals, plants, fungi and bacteria all use pore-forming proteins as cell-killing weapons of mass destruction. Despite their lethal nature and their roles in infection and immunity, how these proteins work remains enigmatic. The outcomes could reveal novel mechanisms general to these proteins and provide fundamental insights in understanding vital physiological processes across all kingdoms of life. Ultimately, this knowledge may guide the design of artificial protein pores that are selective for specific molecules with applications such as measuring metal ions, sugars, pesticides or pollutants. Read moreRead less
The structural basis for MPEG1 mediated assembly of immune complexes. Macrophage Expressed Gene-1 (MPEG1) is an ancient pore forming perforin-like immune effector that is found throughout multicellular life. In humans MPEG1 is found in Macrophages (a type of immune cell) and functions to eliminate a wide range of different infectious microbes. In this study we will study how different modifications and molecular interactions drive MPEG1 function. Crucially our work will provide a framework to ....The structural basis for MPEG1 mediated assembly of immune complexes. Macrophage Expressed Gene-1 (MPEG1) is an ancient pore forming perforin-like immune effector that is found throughout multicellular life. In humans MPEG1 is found in Macrophages (a type of immune cell) and functions to eliminate a wide range of different infectious microbes. In this study we will study how different modifications and molecular interactions drive MPEG1 function. Crucially our work will provide a framework to understand how MPEG1 interacts with the interferon signalling pathway. These data will provide fundamental insight into how perforin-like proteins are controlled and will broadly inform new approaches to modify immune function and molecular signalling events.Read moreRead less