Discovery Early Career Researcher Award - Grant ID: DE190100304
Funder
Australian Research Council
Funding Amount
$416,092.00
Summary
Understanding intramolecular regulation of ubiquitin enzymes. This project aims to combine structural, biophysical and functional studies to characterise how ubiquitin enzymes are regulated. Ubiquitination controls essential cellular pathways in all eukaryotes and this project expects to generate new knowledge regarding the vital regulation of this process. This project expects to develop broadly applicable techniques for investigating protein conformation and self-association as a means of cont ....Understanding intramolecular regulation of ubiquitin enzymes. This project aims to combine structural, biophysical and functional studies to characterise how ubiquitin enzymes are regulated. Ubiquitination controls essential cellular pathways in all eukaryotes and this project expects to generate new knowledge regarding the vital regulation of this process. This project expects to develop broadly applicable techniques for investigating protein conformation and self-association as a means of controlling catalytic activity. The project should significantly increase understanding of several modes of regulation of ubiquitin ligase catalytic activity, and how this controls a myriad of cellular processes. The project will lay the foundation for applied research anti-viral compounds, plant anti-fungals and cancer therapies.Read moreRead less
Australian Laureate Fellowships - Grant ID: FL150100106
Funder
Australian Research Council
Funding Amount
$2,951,945.00
Summary
Bio-metrology and modelling of a complex system: the malaria parasite. Bio-metrology and modelling of a complex system: the malaria parasite: This fellowship project aims to develop a cross-disciplinary program to measure, model and manipulate a complex cellular system — sexual differentiation of the human malaria parasite. Combining life and physical sciences with powerful imaging techniques, the project seeks to develop quantitative biochemical, biophysical and modelling techniques to probe a ....Bio-metrology and modelling of a complex system: the malaria parasite. Bio-metrology and modelling of a complex system: the malaria parasite: This fellowship project aims to develop a cross-disciplinary program to measure, model and manipulate a complex cellular system — sexual differentiation of the human malaria parasite. Combining life and physical sciences with powerful imaging techniques, the project seeks to develop quantitative biochemical, biophysical and modelling techniques to probe a complex system in a way previously not possible. It expects to integrate and correlate thousands of measurements of the dynamic processes inside cells and use these datasets to generate rigorous and sophisticated mathematical models that can predict drivers of commitment for transformation of the parasite to a sexual phase in preparation for transmission to mosquitoes. This holistic approach hopes to deliver new biotechnology and biomedical outcomes, including new ways to combat disease in livestock and humans.Read moreRead less
Revealing molecular detail of DNA triplexes to underpin antigene technology. Variations from the classic DNA double helix structure are proposed to play key roles in a range of cellular processes, particularly gene regulation. However, the biological function and therapeutic potential of these unusual DNA structures are poorly explored, since the fundamental molecular details which govern their formation and interactions with cellular machinery are not well described. This project aims to develo ....Revealing molecular detail of DNA triplexes to underpin antigene technology. Variations from the classic DNA double helix structure are proposed to play key roles in a range of cellular processes, particularly gene regulation. However, the biological function and therapeutic potential of these unusual DNA structures are poorly explored, since the fundamental molecular details which govern their formation and interactions with cellular machinery are not well described. This project aims to develop innovative methods to investigate, and importantly modulate, DNA and RNA triple helix assembly, specificity and molecular interactions. Resulting insights will underpin novel approaches to gene regulation, principally in the context of designing new antibacterial agents to address the antibacterial resistance problem.Read moreRead less
Roadblocks in DNA replication. This project aims to develop the technology to visualise and understand the molecular processes responsible for the faithful copying of cellular DNA in the presence of roadblocks caused by chemical pressures and competing intracellular events. Understanding this process is important as DNA replication is responsible for copying the DNA genetic blueprint of cells and is crucial to all life on earth. This project will have as key outcomes the development of novel mol ....Roadblocks in DNA replication. This project aims to develop the technology to visualise and understand the molecular processes responsible for the faithful copying of cellular DNA in the presence of roadblocks caused by chemical pressures and competing intracellular events. Understanding this process is important as DNA replication is responsible for copying the DNA genetic blueprint of cells and is crucial to all life on earth. This project will have as key outcomes the development of novel molecular visualisation technology and the first molecular description of the dynamic processes used by the DNA-replication machinery to navigate roadblocks. These outcomes should provide significant benefits including enhanced collaboration and scientific capacity in Australia.Read moreRead less
Understanding pore formation by the complement membrane attack complex. The project aims to improve our understanding of the function of the membrane attack complex (MAC). MAC is a large protein complex used by the human immune system to target invading bacteria and parasites by punching holes in the lipid membranes of target cells. The MAC is part of a superfamily of proteins, the MACPF (membrane attack complex/perforin superfamily)/CDC (cholesterol-dependent cytolysins) superfamily, used by an ....Understanding pore formation by the complement membrane attack complex. The project aims to improve our understanding of the function of the membrane attack complex (MAC). MAC is a large protein complex used by the human immune system to target invading bacteria and parasites by punching holes in the lipid membranes of target cells. The MAC is part of a superfamily of proteins, the MACPF (membrane attack complex/perforin superfamily)/CDC (cholesterol-dependent cytolysins) superfamily, used by animals (in venoms and immunity), fungi (in defence) and pathogenic bacteria (in disease). The aim of this project is to image to the highest possible resolution how the MAC form pores in the context of bacterial cells and explore the way it inserts into cells in real time. Intended project outcomes may lay the foundation for applied future research into improved antibiotic delivery and novel pesticide development.Read moreRead less
Next generation dengue diagnostics. The 2009 dengue epidemic was widespread and the largest in North Queensland for 50 years. The outbreak was not quickly contained despite an extensive education program and a mosquito control taskforce. All four types of Dengue were detected, greatly increasing the chance of more severe complications such as Dengue haemorrhagic fever and Dengue shock syndrome. This project will improve our knowledge of Dengue proteins used in tests to diagnose the virus. The ne ....Next generation dengue diagnostics. The 2009 dengue epidemic was widespread and the largest in North Queensland for 50 years. The outbreak was not quickly contained despite an extensive education program and a mosquito control taskforce. All four types of Dengue were detected, greatly increasing the chance of more severe complications such as Dengue haemorrhagic fever and Dengue shock syndrome. This project will improve our knowledge of Dengue proteins used in tests to diagnose the virus. The new knowledge will be used to develop an easy to use test to diagnose Dengue infection early, rapidly and accurately. Effective diagnosis of Dengue will then allow timely implementation of intervention strategies (mosquito control, public advice, isolation and care).Read moreRead less