Using chemistry to illuminate sulfoglycolysis, a major organosulfur pathway. This project aims to develop a detailed molecular description of the sulfoglycolysis pathway, a major pathway involved in cycling an abundant sulfolipid. The project will use an integrated chemical, biochemical and structural approach to illuminate how sulfoglycolysis degrades sulfolipid to access its elemental and energy constituents. Expected outcomes include an advanced understanding of the biosulfur cycle, the devel ....Using chemistry to illuminate sulfoglycolysis, a major organosulfur pathway. This project aims to develop a detailed molecular description of the sulfoglycolysis pathway, a major pathway involved in cycling an abundant sulfolipid. The project will use an integrated chemical, biochemical and structural approach to illuminate how sulfoglycolysis degrades sulfolipid to access its elemental and energy constituents. Expected outcomes include an advanced understanding of the biosulfur cycle, the development of new chemical approaches to manipulate sulfur cycling for agricultural and biotechnology applications, and deepened ties to leading international researchers. Potential benefits include new strategies to reduce dependence on agricultural fertilisers, promote gut wellbeing, and control insect pests.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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE160100047
Funder
Australian Research Council
Funding Amount
$380,000.00
Summary
Distributed facility for fragment based drug discovery. Distributed facility for fragment based drug discovery:
The facility aims to provide researchers with the ability to generate small molecules that modulate therapeutically and biologically important protein targets. Fragment-based drug design (FBDD) provides a rational approach to generate such biologically active compounds. The facility is designed to allow researchers throughout Australia to access the necessary infrastructure to underta ....Distributed facility for fragment based drug discovery. Distributed facility for fragment based drug discovery:
The facility aims to provide researchers with the ability to generate small molecules that modulate therapeutically and biologically important protein targets. Fragment-based drug design (FBDD) provides a rational approach to generate such biologically active compounds. The facility is designed to allow researchers throughout Australia to access the necessary infrastructure to undertake FBDD projects against a range of biologically important targets. The facility aims to enable access to high-throughput nuclear magnetic resonance spectroscopy and surface plasmon resonance, and to generate the capacity for automation in chemical synthesis and sample preparation to expedite the development of novel bioactive molecules. The development of better approaches to hit development may benefit many researchers in Australia employing FBDD.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
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
New Protocols for the Chemical Synthesis of Biologically Relevant Systems. Enzyme- and metal-catalysed processes will be developed and exploited for the purpose of establishing concise syntheses of biologically active and otherwise inaccessible natural products and their analogues. The range of structures to be targeted is structurally diverse and these have the potential to act as agrochemicals and/or as therapeutic agents for the treatment of a range of disease states in mammals including bact ....New Protocols for the Chemical Synthesis of Biologically Relevant Systems. Enzyme- and metal-catalysed processes will be developed and exploited for the purpose of establishing concise syntheses of biologically active and otherwise inaccessible natural products and their analogues. The range of structures to be targeted is structurally diverse and these have the potential to act as agrochemicals and/or as therapeutic agents for the treatment of a range of disease states in mammals including bacterial and viral infections, neuro-degenerative conditions and impaired cognitive function. Anti-angiogenic compounds that control otherwise unregulated cellular growth may also arise from these studies. The generation of new, homochiral metabolites for use in chemoenzymatic synthesis should also emerge from this project.Read moreRead less
Harnessing strain for chemical synthesis: The cyclopropane angle. This project aims to develop new reaction pathways of cyclopropanes, the smallest and most strained monocyclic ring systems, but which are also stable and easily prepared. Cyclopropanes have unique capacities to serve as highly effective building blocks in the synthesis of a wide range of otherwise difficult to access and biologically active molecular frameworks. This project will use cyclopropanes to rapidly assemble biologically ....Harnessing strain for chemical synthesis: The cyclopropane angle. This project aims to develop new reaction pathways of cyclopropanes, the smallest and most strained monocyclic ring systems, but which are also stable and easily prepared. Cyclopropanes have unique capacities to serve as highly effective building blocks in the synthesis of a wide range of otherwise difficult to access and biologically active molecular frameworks. This project will use cyclopropanes to rapidly assemble biologically active systems, especially pharmaceutically or agrochemically valuable natural products and relevant analogues.Read moreRead less
Enabling Methodologies for the Synthesis of Biologically Active Compounds. This project seeks to establish flexible methods of chemical synthesis for creating new molecular scaffolds capable of achieving selective enzyme inhibition. The approach aims to exploit the vast and biologically-programmed structural diversity associated with natural products. Unique, small molecule organic compounds will be obtained that reveal details of the operation of key enzymes in bacterial and mammalian systems. ....Enabling Methodologies for the Synthesis of Biologically Active Compounds. This project seeks to establish flexible methods of chemical synthesis for creating new molecular scaffolds capable of achieving selective enzyme inhibition. The approach aims to exploit the vast and biologically-programmed structural diversity associated with natural products. Unique, small molecule organic compounds will be obtained that reveal details of the operation of key enzymes in bacterial and mammalian systems. Such new knowledge would allow for the design of highly selective therapeutic agents relevant to the treatment of a range of diseases including bacterial infections, diabetes and cancer. The high-end scientific training and privileged forms of matter arising from this work would provide major benefit to the biotech sector.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