Discovery
New modes of action, improved efficacy, stability and durability
Predicting bioactive molecules for plant health and agricultural applications
Project: A platform for functional prediction and validation of undiscovered secondary metabolites in Actinobacteria (2023-2027)
Part of the Advanced Engineering Biology Future Science Platform
The team: Marta Gallart (Project leader), Louise Thatcher, Oliver Mead, Vincent Nowak, Sally Buck, Lygie Esquirol, Alex Gloria, and Robert Speight.
The challenge
Biopesticides such as microbial-derived bioactive molecules offer a safer, sustainable and more effective solution to maintain high productivity agricultural systems. Members of the Actinobacteria phylum are a rich source of bioactive natural molecules, including herbicidal secondary metabolites. Advances in next generation sequencing and analysis allow us to predict secondary metabolite gene clusters and indicate that Actinobacteria can produce many more secondary metabolites than previously thought. The challenge is how can we predict the chemistries and the biological function of these novel natural molecules to fast-track the development of new biopesticides, and how can we produce them cost effectively at scale for commercial uptake?
Our response
Using integrative omics, engineering biology and metabolic modelling technologies, we are helping to solve these challenges by developing a high-performance pipeline for the prediction and discovery of novel bioactive molecules encoded by secondary metabolite gene clusters in Actinobacteria. The project aims to exploit a CSIRO Actinobacteria strain collection to uncover its hidden chemical potential and create a database that integrates genomes, advanced genome mining, phenotyping and metabolomics data, followed by downstream chemical and biological characterisation.
Impact
The search for new bioactive molecules is hindered by our ability find them, to predict their function and biological activity, and to produce them at low cost. This project aims to overcome these obstacles through new, faster, and more accurate predictive methods coupled with high throughput, miniaturised experimental systems for functional testing. The Actinobacteria-based bioactive molecule discovery, functional prediction and precision bioproduction pipeline will advance us beyond traditional ‘one strain one molecule’ approaches to a foundational platform using streamlined approaches for fast-tracked bioproduction of multiple molecules. Such potential can be tailored towards other crop protection products (biofungicides, bioinsecticides), or leveraged towards pharmaceuticals, other agrichemicals, or the production of food additives.
Learn more here
Can engineering biology feed more people with fewer resources?
Overcoming a chemically limited future for weed, pest and disease control in agriculture
Durable solutions for pest control in agriculture. Harnessing the invisible and invaluable microbes that enhance our food, environment and health
Finding microbial functions in plant microbiomes that promote resilient crops
Project: Getting the right microorganisms among the thousands found in soil and plant material is challenging, but the benefits for agriculture are worth it (2022-2025)
Part of the Microbiomes for One Systems Health Future Science Platform
The team: Louise Thatcher (Project leader), Lachlan Dow, Marta Gallart, Simon Law, Luke Barrett, Roshan Regmi, Gupta Vadakattu.
The challenge
Plant microbiomes – more than just disease. Plants have a community of microbes associated with them, known as a microbiome. Some of these microbes are detrimental to the plant, causing disease and ultimately killing the plant. Other microbes are beneficial, helping the plant acquire nutrients and fend off these pathogens. In total, this consortium of microscopic organisms is a huge, largely untapped source of new methods to improve outcomes for crops.
Piecing together plant microbiomes – where to begin? Despite the promise of new ways to improve plant health, microbiomes are extremely complicated communities of individual species. Many of these species have never been grown in laboratory conditions, making them difficult to study. This means knowing the important species in microbiomes and how to foster the preferred species is still unknown.
Our response
Finding the right stuff. CSIRO is working towards identifying the characteristic functions shared by healthy, productive plant microbiomes. By combining modern techniques such as transcriptomics and metabolomics, we can deliver insights into the plant’s microbiome in unprecedented detail. Transcriptomics provides information like which genes and functions are switched on, while metabolomics tells us if the plant (or its microbiome) are producing any defensive chemicals like antifungals. These two methods are “culture independent”, meaning that we can study microbes without first needing to grow them in the lab.
Impact
Through these insights, we can then build a predictive framework from which plant microbiomes can be tailored for more productive and sustainable agriculture. For example, these results could lead to agricultural practices that promote natural antifungal production where it’s needed, before chemical intervention is required. It may also lead to new biocontrol agents, by harnessing previously unseen microbial functions.
Learn more here
Understanding microbes and their metabolites: Tools for accelerated discovery
The team: our whole team collaborates to achieve this goal. Reach out to Team Leader Marta Gallart
The challenge
The global diversity of microbes is massive, and most of these microbes are relatively under characterised. Microbes generate thousands of unique compounds known as metabolites. While these have specific functions in the microbes they come from, microbial metabolites can have different and sometimes valuable impacts on other living things. These impacts include things like antibiotic, antifungal, herbicidal, pesticidal, or growth stimulating properties. But because there are so many microbial species out there, and because each of them produce so many metabolites, it can be like searching for a needle in a haystack.
Our response
To tackle the challenge of searching through all of this diversity, we have developed a set of high throughput laboratory tools and pipelines. These tools streamline the searching process, making it as efficient as possible. One such tool is an imaging method, using the BMIC facilities at the CSIRO Black Mountain site. These approaches allow us to document and measure the impact that microbial metabolites have on other living things such as plants and insects, in turn, allowing us to narrow down which microbes are having the largest desired impacts as quickly as possible.
Another tool we have developed utilises a metabolomics pipeline, developed within the team. This tool uses the analytical chemistry facilities at Black Mountain and helps us to quickly identify known metabolites within microbes. These pipelines can also be used for novel compound discovery, allowing the team to link activity to new compounds.
The multi omics tools within the team can be used with our metabolomics pipelines to assist in compound characterisation, but also to predict which microbes might produce valuable metabolites and better understand how those metabolites are produced. The multi omics tools focus on the Actinobacteria collection used within the team, resulting in a comprehensive library of the genomic, transcriptomic, and proteomic properties for each bacterium within the collection. This represents an incredibly valuable dataset that can be used within the team to better understand our microbes and rapidly address new challenges that we are presented with.
Impact
These tools allow our team to quickly and efficiently search through microbial diversity to find microbial metabolites with desired properties that can improve crop health. By using these tools in combination, we are not only able to find metabolites, but also to gain an understanding of what they are, what they might do, and how they might be made. These are incredibly valuable insights in our search for sustainable agricultural solutions.
