ALMOND: Agriculture Living Machine of Operational Nano Droplets

Lead Research Organisation: CARDIFF UNIVERSITY
Department Name: Welsh School of Pharmacy


Industrialisation of the agricultural sector has been essential for feeding the growing global population, but has resulted in increased chemical burden on ecosystems with the use of chemical pesticides and insecticides to protect crop growth.

The global seed treatment market size was valued at $13.4B in 2022 and is expected to grow ~10 % annually until 2030. US farmers annually spend >$575 million on fungicides to provide a commercial crop gain of c.$13 billion. This reflects the huge role of agrichemicals in current usage to maintain global food supplies.

The ecological impacts of chemical pesticides and insecticides, including environmental persistence, ecosystem toxicity, water contamination, foodchain accumulation and emerging resistance, have become increasingly apparent and have seen a move away from their use. However, alternative solutions are not without challenge.

There is increasing interest in harnessing naturally occurring microorganisms (biopesticides) in or on soil or within seed-coatings to help protect crops, and this approach has seen much success with species such as Bacillus thuringiensis and Lysinbacillus sphaericus, and insect-active fungi and viruses. However, a number of highly promising specific pesticide and insecticides biocactive molecules made by micro-organisms that can protect crops are difficult to harness in practice due to potential concerns about the micro-organisms being able to cause infection in people or animals, until proven safe. Similarly, the active compounds themselves are often unstable or difficult to purify, so these are challenging to use alone. We have identified novel bioactive polyyne, cepacin in Burkholderia bacteria and discovered its biosynthetic pathway. Cepacin has fungicidal activity that protects germinating crops against damping off disease, as such these specialised metabolites represent promising novel bioactives.

In this project we will use cutting edge 3D-printed microfluidics to produce non-reproducing, environmentally benign artificial cells - artificial engineered materials inspired by biology based on the cell membrane. These artificial cells contain networked compartments, separated by lipid bilayers, much like biological cells, and can serve as biochemical microfactories to synthesis these promising pesticide and insecticide biochemicals locally, to enhance crop health. By formulating these artificial cells as crop seed coatings in biodegradable hydrogel shells, the protective effects are localised exactly where needed. The artificial cells will be programmed to respond to genetic cues when the seed germinates, to activate pesticide protection. In this way the artificial cells can respond in different ways in different circumstances of plant health, disease or in the presence of different insect predators.

Importantly these systems afford flexibility and a combinatorial ability to assemble pathways and toxins not normally found together, without creating transgenic organisms that that could prove challenging to license. In this way, we can use different active biomolecules in combination in a single synergistic formulation and also combine with existing biopesticides for enhanced function, that includes nitrogen fixation for enhanced crop growth and soil health and carbon capture and conversion to energy to power the artificial cell metabolism .

Technical Summary

ALMOND aims to develop a technology platform of bio-hybrid materials and artificial cells to enhance the protection and growth of crops by creating functionally augmented seed coatings and stand-alone agri-capsules. Composed of biodegradable hydrogel scaffold of controlled composition and containing functional artificial cells (ACs), and synergistic live bacterial counterparts where appropriate, these environmentally compatible materials will represent the next generation soft-matter smart materials for enhancing crop protection from infection and predation.

ALMOND represents a new paradigm of safe, green technology for the development of synergistic crop supportive micro-environments, underpinned by functional artificial cells (ACs). By creating hybrid materials composed of hydrogel seed-coating with embedded responsive, re-configurable, and biochemically programmable ACs, to achieve control of the local environment for the benefit of crop growth. This will harness the biological activity of emerging natural product pesticides, that are otherwise challenging to implement in practice, such as Burkholderia produced polyynes that protect against damping off disease, and custom insect targeting bioinsecticidal protein toxins such as Hv1a fusion constructs, affording highly targeted pest specificity.

Compartmentalised ACs built with precision, order, and with integrated metabolisms - in a design mirroring living systems - can communicate with the environment via membrane-based chemistry. With such approaches ACs may be programmed to respond to the status of neighbouring live cells of the plant or pathogen, synthesising and releasing biopesticides to protect the developing seedling. In this way multiple pathways can be combined and synergised with existing live biofertilisers/biopesticides affording combinatorial ability to assemble pathways and toxins not normally found together, without creating transgenic organisms that that could prove challenging to license.


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