Discovery Early Career Researcher Award - Grant ID: DE180100418
Funder
Australian Research Council
Funding Amount
$365,058.00
Summary
Novel chemical tools to study cathepsin X activation. This project aims to develop new chemical tools that can measure the specific activation of cathepsin X in cells, tissues, and live animals, as well as specific inhibitors for cathepsin X. The cysteine protease cathepsin X mediates basic biological functions that are essential for life, including cell communication, phagocytosis, immune maturation and neuritogenesis. The outcomes should benefit the wider research community. They could have lo ....Novel chemical tools to study cathepsin X activation. This project aims to develop new chemical tools that can measure the specific activation of cathepsin X in cells, tissues, and live animals, as well as specific inhibitors for cathepsin X. The cysteine protease cathepsin X mediates basic biological functions that are essential for life, including cell communication, phagocytosis, immune maturation and neuritogenesis. The outcomes should benefit the wider research community. They could have long-term implications for health and disease, and deliver economic benefits through commercialisation of the novel tools.Read moreRead less
Biosynthesis and functions of two phytotoxins in Septoria nodorum blotch. This project aims to investigate how a fungal plant pathogen makes and uses small bioactive molecules to facilitate infection. It will characterise the function of the genes and enzymes involved in the biosynthesis of a light-activated phytotoxic molecule and a potential anti-plant defence molecule found in the pathogenic wheat fungus Parastagonospora nodorum, and investigate their contribution to disease development. Expe ....Biosynthesis and functions of two phytotoxins in Septoria nodorum blotch. This project aims to investigate how a fungal plant pathogen makes and uses small bioactive molecules to facilitate infection. It will characterise the function of the genes and enzymes involved in the biosynthesis of a light-activated phytotoxic molecule and a potential anti-plant defence molecule found in the pathogenic wheat fungus Parastagonospora nodorum, and investigate their contribution to disease development. Expected outcomes include better understanding of plant-microbe interactions, disease management strategies, technologies for identifying biosynthetic pathways in other fungi, and enzyme technology for synthesising molecules. This could lead to new herbicides, biopesticides and drugs.Read moreRead less
Resurrecting Ancient Proteins to Unlock New Catalytic Activity. This project aims to study the proteins that nature uses to make penicillin and related antibiotics, and their prehistoric ancestors. By doing so, the project expects to deepen understanding of these important processes, open up ways to make new antibiotics, and generate new knowledge about protein evolution. Intended outcomes include new biocatalysts based on the ancient ones, new antibiotic compounds active against resistant bacte ....Resurrecting Ancient Proteins to Unlock New Catalytic Activity. This project aims to study the proteins that nature uses to make penicillin and related antibiotics, and their prehistoric ancestors. By doing so, the project expects to deepen understanding of these important processes, open up ways to make new antibiotics, and generate new knowledge about protein evolution. Intended outcomes include new biocatalysts based on the ancient ones, new antibiotic compounds active against resistant bacteria, and a richer understanding of how these proteins have evolved over the last 4 billion years. This promises significant benefits in the form of new ways to address the challenge posed by antimicrobial resistance to antibiotics, which is a serious threat to the continued effectiveness of current antibiotics.Read moreRead less
Fungal Ribosomally Synthesised and Post-translationally Modified Peptides. Fungi produce an array of molecules called secondary metabolites (SMs) that impact on everyday life (e.g. penicillin). This project aims to investigate a new class of fungal peptide SMs called RiPPs which are structurally unique from existing molecules and offer the exciting prospect of harbouring new and novel biological activities. This project expects to discover the mechanisms of RiPP synthesis and their biological ro ....Fungal Ribosomally Synthesised and Post-translationally Modified Peptides. Fungi produce an array of molecules called secondary metabolites (SMs) that impact on everyday life (e.g. penicillin). This project aims to investigate a new class of fungal peptide SMs called RiPPs which are structurally unique from existing molecules and offer the exciting prospect of harbouring new and novel biological activities. This project expects to discover the mechanisms of RiPP synthesis and their biological roles in plant pathogenic fungi, and uncover and engineer novel RiPPs with desired bioactivities. The expected outcome from this project will be a seminal advance in fungal SM biology which should provide significant benefits through the generation of exciting new lead molecules for the agricultural and medical industries.Read moreRead less
Allosteric and Bitopic Ligands Acting at G Protein-Coupled Receptors. This project seeks to gain a more detailed understanding of the mechanisms of the function of G protein-coupled receptors (GPCRs) using novel chemical tools. GPCRs are the largest group of cell surface signalling proteins and are responsible for the regulation of numerous vital physiological functions. They are the target of over 30 per cent of currently used pharmaceuticals. Despite their importance, much remains to be learne ....Allosteric and Bitopic Ligands Acting at G Protein-Coupled Receptors. This project seeks to gain a more detailed understanding of the mechanisms of the function of G protein-coupled receptors (GPCRs) using novel chemical tools. GPCRs are the largest group of cell surface signalling proteins and are responsible for the regulation of numerous vital physiological functions. They are the target of over 30 per cent of currently used pharmaceuticals. Despite their importance, much remains to be learned about the regulation of GPCRs by small molecules. This project aims to address this gap by focusing on novel regions on these proteins, termed allosteric sites, to explore novel modes of GPCR regulation which may offer the potential of identifying pathway selective agents.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE170100058
Funder
Australian Research Council
Funding Amount
$372,000.00
Summary
Molecular reporters for measuring proteostasis capacity in cells. This project aims to develop fluorescent dyes to report on the change in unfolded protein load, which reflects the proteostasis status in real time in cells under stress conditions. Proteostasis is a housekeeping process cells undertake to maintain the proper folding and functions of proteins. Perturbation of proteostasis has been linked to neurodegenerative diseases, but chemical probes cannot measure the proteostasis capacity in ....Molecular reporters for measuring proteostasis capacity in cells. This project aims to develop fluorescent dyes to report on the change in unfolded protein load, which reflects the proteostasis status in real time in cells under stress conditions. Proteostasis is a housekeeping process cells undertake to maintain the proper folding and functions of proteins. Perturbation of proteostasis has been linked to neurodegenerative diseases, but chemical probes cannot measure the proteostasis capacity in cells. Intended outcomes include a mechanistic understanding of the relationship between protein misfolding, aggregation and proteostasis. This is expected to ultimately benefit the diagnosis of protein folding diseases, including dementia, and improve the quality of life.Read moreRead less
CRISPR-based pathway activation for bioactive molecule discovery in fungi. Fungi produce an incredible array of unique bioactive molecules, many of which have contributed greatly to humanity (e.g. the antibiotic penicillin, which has saved millions of lives since its discovery). DNA sequencing has revealed many fungi contain the genetic instructions to produce new molecules that have not been seen previously. However, these genes are “switched off" by default and cannot be accessed. This project ....CRISPR-based pathway activation for bioactive molecule discovery in fungi. Fungi produce an incredible array of unique bioactive molecules, many of which have contributed greatly to humanity (e.g. the antibiotic penicillin, which has saved millions of lives since its discovery). DNA sequencing has revealed many fungi contain the genetic instructions to produce new molecules that have not been seen previously. However, these genes are “switched off" by default and cannot be accessed. This project will develop innovative new methods to "hot-wire" these genes, allowing them to turn on and produce a treasure trove of new bioactive molecules. The outcomes of this project will transform our abilities to tap into the hidden potential of fungi to generate new lead molecules for the agricultural and medical industries.Read moreRead less
Unleashing the Hidden Chemical Diversity in Australian Fungi. This project aims to exploit an exclusive genomic resource consisting of >150 unique Australian filamentous fungi that has been built in a university-industry collaboration for genomic-guided biodiscovery. The genome sequence of these fungi revealed extensive hidden genetic instructions for production of novel biologically active molecules. The project will apply cutting-edge synthetic biology and chemical tools to tap into the hidden ....Unleashing the Hidden Chemical Diversity in Australian Fungi. This project aims to exploit an exclusive genomic resource consisting of >150 unique Australian filamentous fungi that has been built in a university-industry collaboration for genomic-guided biodiscovery. The genome sequence of these fungi revealed extensive hidden genetic instructions for production of novel biologically active molecules. The project will apply cutting-edge synthetic biology and chemical tools to tap into the hidden genomic potential of these Australian fungi. Expected outcomes of this project include new fine chemicals and lead molecules with desirable bioactivies. This will provide significant benefits to Australia's economy through the discovery of new pharmaceuticals, veterinary products and agrichemicals.Read moreRead less
The hidden secondary metabolite biosynthetic potential of fungi. This proposal aims to develop synthetic biology tools to allow rapid access to the hidden metabolites encoded in fungal genomes and discover how they interact with plant and animal hosts. Genome sequencing reveals that fungi harbour vast hidden potential for biosynthesis of bioactive small molecules. The lack of tools to efficiently access this hidden potential has hindered the ability to develop this uncharted chemical diversity f ....The hidden secondary metabolite biosynthetic potential of fungi. This proposal aims to develop synthetic biology tools to allow rapid access to the hidden metabolites encoded in fungal genomes and discover how they interact with plant and animal hosts. Genome sequencing reveals that fungi harbour vast hidden potential for biosynthesis of bioactive small molecules. The lack of tools to efficiently access this hidden potential has hindered the ability to develop this uncharted chemical diversity for pharmaceutics and agriculture, and understand their biological roles in pathogens. Expected outcomes include sources of bioactive molecules and better management of fungal diseases in crops and humans.Read moreRead less
Metals in biocatalysis. Metals and enzymes are essential for the chemistry of life. This project will aim to garner the potential of metal-dependent enzymes to develop new drugs against osteoporosis, combat the spread of antibiotics resistance and optimise some of these enzymes to detoxify pesticide-polluted environments, thus contributing to global health and food security.