Suppression Of Immunity By The Malaria Parasite Antigen Plasmodium Falciparum Erythrocyte Membrane Protein-1 (PfEMP-1)
Funder
National Health and Medical Research Council
Funding Amount
$96,698.00
Summary
The malaria parasite P. falciparum infects red blood cells and makes the cells put on their surface a protein called PfEMP-1. The parasite can effectively “hide” by constantly changing this protein and making it unrecognizable by the immune system. PfEMP-1 can also suppress the immune system so that it can’t respond adequately to infection. Therefore, understanding PfEMP-1 function is important. I will investigate how PfEMP-1 can do this by looking at its cross talk with the immune system.
Investigation of the mechanisms underlying successful placentation. The overall aim of this project is to provide novel insights into the basic cellular processes that underpin placental development and to improve our ability to manipulate mammalian reproduction, both human and animal. The placenta is critical for intrauterine development because it determines the level of nutrition, oxygenation and maternal tolerance to the developing foetus. The project intends to explore the role of prorenin ....Investigation of the mechanisms underlying successful placentation. The overall aim of this project is to provide novel insights into the basic cellular processes that underpin placental development and to improve our ability to manipulate mammalian reproduction, both human and animal. The placenta is critical for intrauterine development because it determines the level of nutrition, oxygenation and maternal tolerance to the developing foetus. The project intends to explore the role of prorenin and its receptor as a novel mechanism driving placentation. Applications for expected project outcomes may include improved breeding of threatened animal species and economically valuable domestic animals as well as improved health care and fertility control for domesticated pets and feral animals. Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE180100524
Funder
Australian Research Council
Funding Amount
$365,057.00
Summary
Manipulating selected inflammatory responses in macrophages. This project aims to define the structural and functional interactions of a new transmembrane adaptor SCIMP. SCIMP has recently been shown to effect the inflammatory pathway. The project outcomes will include the first structure of this unconventional complex. The project will have significant flow on benefits including new knowledge and new protein methodologies for end-users in research and industry, and ultimately economic impact.
Novel mechanisms of early growth response-1 activation through the epidermal growth factor receptor. This project will expand our knowledge of how cytokines and growth factors switch on signalling pathways from the cell surface to the nucleus. Unique antibodies will characterise regulatory routes, state-of-the-art microscopy will define dynamic patterns of receptor co-assembly, and in vivo studies will show receptor crosstalk in animal models.
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
Nano-scale organisation of cellular adhesions. Cell migration is a key aspect of many normal processes but also of diseases such as cancers. This project will use a novel fluorescence microscope that can see single proteins to identify how cell adhesions are formed, remodelled and disassembled. This knowledge will help to design better drugs against cancers and novel implantable materials.
Discovery Early Career Researcher Award - Grant ID: DE140100558
Funder
Australian Research Council
Funding Amount
$389,220.00
Summary
Caveolae as structural mechanosensors: a link between the intra and extracellular environments? How cells perceive and respond to mechanical cues are fundamental questions in cellular biology. Caveolae are invaginations of the plasma membrane which flatten into the bulk membrane in response to increased membrane tension. This project aims to validate this response at the molecular level in a physiological context. Specifically, the project will investigate how the caveola response coordinates wi ....Caveolae as structural mechanosensors: a link between the intra and extracellular environments? How cells perceive and respond to mechanical cues are fundamental questions in cellular biology. Caveolae are invaginations of the plasma membrane which flatten into the bulk membrane in response to increased membrane tension. This project aims to validate this response at the molecular level in a physiological context. Specifically, the project will investigate how the caveola response coordinates with the extracellular matrix as well as study the fate of caveolar proteins released from caveolae. Besides the establishment of new methodologies, the findings will highlight the role of caveolae in the short and long term adaptive responses to mechanical cues and enhance understanding of how cells integrate the extracellular and intracellular environments.Read moreRead less
DNA nanotechnology for controlled antigen presentation to T cells. The project aims to present individual antigens to T cells and to image T cell receptor signalling with single molecule microscopy. Combining DNA origami nanotechnology with single molecule imaging should reveal the sensitivity of T cell signalling. A DNA force sensor will determine whether mechanical forces contribute to antigen discrimination. The project will use the nanotechnology strategy to identify antigen-specific T cells ....DNA nanotechnology for controlled antigen presentation to T cells. The project aims to present individual antigens to T cells and to image T cell receptor signalling with single molecule microscopy. Combining DNA origami nanotechnology with single molecule imaging should reveal the sensitivity of T cell signalling. A DNA force sensor will determine whether mechanical forces contribute to antigen discrimination. The project will use the nanotechnology strategy to identify antigen-specific T cells in tissue. The project is expected to advance understanding of T cell biology, and contribute to DNA nanotechnology and super-resolution microscopy whilst providing fundamental insights into antigen recognition by T cells and ultimately derive clinically relevant practical applications.Read moreRead less
Phosphoinositide regulation of lysosome reformation during autophagy. This project aims to investigate a new critical step in the autophagy pathway, autophagic lysosome reformation, a fundamental, evolutionarily conserved mechanism for cellular homeostasis. By combining gene function studies with advanced cellular imaging techniques, this project will investigate the dynamic membrane changes that drive this lysosome recycling pathway and how it is regulated by a hierarchical succession of specif ....Phosphoinositide regulation of lysosome reformation during autophagy. This project aims to investigate a new critical step in the autophagy pathway, autophagic lysosome reformation, a fundamental, evolutionarily conserved mechanism for cellular homeostasis. By combining gene function studies with advanced cellular imaging techniques, this project will investigate the dynamic membrane changes that drive this lysosome recycling pathway and how it is regulated by a hierarchical succession of specific enzymes. The expected outcome will be to re-define the archetypical autophagy pathway and characterise novel mechanisms by which it is controlled. This project will reveal new fundamental biological processes, and act as a framework for developing new imaging modalities and tools for studying autophagy.Read moreRead less
Molecular mechanisms of cyclic Adenosine Monophosphate (AMP) induced apoptosis. Cyclic Adenosine Monophosphate (cAMP) is an important cellular chemical necessary for cell growth. However, de-regulated cAMP production in response to altered physiology can result in cellular death or apoptosis. This is attributed to the development of certain human diseases and this project aims to understand the molecular mechanism behind this process.