The Problem

Over the next 35 years, the world’s growing population will demand more food than has ever been produced in human history [1]. After decades of steady decline in the prevalence of moderate and severe food insecurity, since 2015 these numbers have begun to increase once again. According to the Food and Agriculture Organization of the United Nations, we are not on track to achieving the Sustainable Development Goal of Zero Hunger. Far from it, every year the gap between where we want to be and where we are widens [2], as many of you who are reading this might be witnessing in your own local communities. Food insecurity is a complex and interconnected issue, with its drivers being myriad, ranging from conflict, to climate extremes and economic crises, as well as historic and growing inequalities. It is clear that if we are to feed the 690 million people hungry today, and the additional 2 billion individuals who will be part of our world in 2050, increasing agricultural productivity is necessary via a transformation of our agrifood systems to be more resilient and sustainable [3].

A major obstacle in achieving Zero Hunger, that can be appropriately addressed using synbio, are plant fungal diseases. Every year, plant diseases result in an average yield loss of 10–15% of the world's major crops [4]. Of these, 70-80% are caused by pathogenic fungi [5]. The damage caused by fungi to rice, wheat and maize alone costs global agriculture 60 billion dollars per year [6]. It’s important to highlight the scale of this problem, and the grave risk fungi pose to our supply of staple crops. Today, accounting for all the advances of “twenty-first-century agriculture”, one in every eight crop plants on average will fail to yield due to fungal disease. In resource-poor areas, where crop protection levels are significantly lower or non-existing, yield losses can range from 50 to 100% [7].This problem is only projected to get worse with time. Rising temperatures, attributable to climate change, combined with the decline in genetic diversity of our crops, have contributed to a perfect storm in pathogen emergence [8].

Frequent genetic mutations allow fungi to circumvent the defense mechanisms of resistant wheat cultivars, as well as develop resistance to commonly used synthetic fungicides [9]. Furthermore, the time delay between the onset of the infection and the first visible symptoms makes early detection extremely difficult. Where current solutions fall short is deploying in the most effective time window. In fact, it has been shown that the timely application of fungicides at the early stages of infection could represent the difference between life or death of a wheat field [10].

Today, farmers must rely on unselective spraying of fungicides as both a curative and preventative measure. Speaking to individual farmers in Europe and India, as well as experts in the field from the CIMMYT and World Veg Centre, we know that the threat of fungal pathogens is as dire as ever, with farmers spraying their crop up to 8 times in a single season but epidemic level outbreaks happening regardless.

According to researchers [11], the need for new disease interventions is critical, with the most effective having the following features:
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1. Efficacy against a broad range of crop pathogens;
2. Attack essential processes in fungal pathogens in multiple ways, to limit resistance development;
3. Present low toxicity to non-target organisms, including humans, animals and plants;
4. Activate the plant defence system, thereby priming the plant for a potential pathogen attack.

Harnessing the natural diversity and biocontrol properties of living systems, the tools that synthetic biology provides could be key in developing the next most-effective disease control strategy.

The Solution

We have devised a non-toxic, broad-spectrum bio-fungicide, consisting of a B. subtilis bacterial spore system that eliminates the time lag between diagnosis and treatment. Natural strains of this bacteria are present in the soil microbiome and have been found to act as excellent biocontrol agents, whilst being completely nonpathogenic nor toxigenic to humans, animals, or plants [12].

Figure 1: Sporadicate's workflow

Our project’s design is based on a sense and response system. We modify B. subtilis spores to display chitinases on their surface, capable of breaking down the chitin-rich outer coat of pathogenic fungi; this includes both fungal spores and vegetative cells, forms in which fungi infect plants. This process generates chitin monomers, a biomarker universal to all fungal pathogens and an inducer of plant innate immunity. Our B. subtilis spores would also be modified to exclusively display a mutant germinant receptor, engineered to be capable of binding to chitin monomers. Upon binding, a cascade is triggered, enabling germination of B. subtilis into its bacterial form. Within four minutes post-detection, the growing colony of B. subtilis cells begin to produce different antifungal lipopeptides effective at eliminating fungal pathogens. Thus, with a single spray of B. subtilis spores, we can target fungal pathogens over space and time, achieving both early detection and treatment.

These modification would be introduced using a self-digesting plasmid, which employs the use of CRISPR to enable our spores to be completely free of foreign DNA – meaning that our product would simply consist of wildtype bacteria produced in response to the detection of the biomarker of interest, ensuring high biosafety standards. The high durability of spores makes our system incredibly robust and widely applicable.

As such, we expect our platform to disrupt the current fungicide market. Our competitors in the biofungicide space are focused on replacing chemical fungicides with more sustainable options and several emerging players are developing targeted fungicides, however none are addressing the issue of timely application.

Learn more about our design choices, experimental design, and supporting entrepreneurship!

The Impact

As this project tackles food security through a more sustainable and equitable solution to fungal diseases, it confers significant economic, social and environmental benefits.

Through the innate durability of spores and their cost-effectiveness, our product has been designed with accessibility in mind. This means we can effectively address the threat of fungal diseases in the regions of the world most at risk, with a tool that can be easily adopted by subsistence and smallholder farmers who carry the majority of the burden of staple crop production, such as wheat, there [13]. Percentage yield losses are higher in such areas (eg. Indian subcontinent and Sub-Saharan Africa) due to the difficulties in the implementation of existing solutions such as expensive novel resistant cultivars or fungicides. The climactic conditions also greatly favour the spread of pathogenic fungi leading to above average regional yield losses, reaching up to 100% in severe cases such as with wheat stripe rust [14]. Such regional losses not only affect the livelihood of the farming community but severely damage the food security of the area leading to an increase in hunger and extreme poverty. As is well-studied, the consequences of hunger not only severely affects quality of life but stunts development towards a more promising future. Our project can mitigate the impact of pathogenic fungi by being non-race specific and applicable to different crop varieties [15].

According to the USAID, a 1% increase in food prices can be projected to result in 10 million more people falling into extreme poverty worldwide [16]. With geopolitical factors resulting in sharp increases in fertiliser, seed and fuel costs, our product could help soften the impact with a reduction in the costs and losses associated with fungal diseases, the primary biotic stressor affecting staple crop production.

Environmental quality will benefit from our product as well. It is an alternative to the current fungicides on the market, which have been shown to leach into soil and groundwater, killing a wide range of organisms and disturbing aquatic biota [17]. Today, farmers must rely on unselective, repetitive spraying of fungicides as both a curative and preventative measure. These not only damage the environment but pose a health-risk to those exposed to them, with studies showing maternal exposure to crops that were sprayed with fungicides were associated with adverse and gender-specific effects on infant neurodevelopment [18]. Our product does not have such toxic effects on the environment and will require fewer applications. B. subtilis is already naturally occurring in the soil microbiome of wheat crops and is known to confer several advantages being classified as a plant growth promoting rhizobacteria (PGPR) [19]. By reducing yield loss, our product ensures that more environmental resources like land, water and nutrients will not go to waste on dead crops.

References

[1] ‘The challenge’ Global Food Security. Available at: https://www.foodsecurity.ac.uk/challenge/ (Accessed: 6 June 2022).

[2] Steinberg, G., & Gurr, S. J. (2020). Fungi, fungicide discovery and global food security. Fungal genetics and biology : FG & B, 144, 103476. https://doi.org/10.1016/j.fgb.2020.103476

[3]'Latest issue: The State of Food Security and Nutrition in the World 2022' (2021) Food and Agriculture Organization of the United States. Available at https://www.fao.org/publications/sofi/2022/en/

[3] United Nations. 2022. Goal 2: Zero Hunger. [online] Available at: https://www.un.org/sustainabledevelopment/hunger/ [Accessed 13 October 2022].

[4] www.fao.org. (n.d.). FAO - News Article: Climate change fans spread of pests and threatens plants and crops, new FAO study. [online] Available at: https://www.fao.org/news/story/it/item/1402920/icode/ [Accessed 13 Oct. 2022].

[5] Peng, Y., Li, S., Yan, J., Tang, Y., Cheng, J., Gao, A., Yao, X., Ruan, J. and Xu, B., 2021. Research Progress on Phytopathogenic Fungi and Their Role as Biocontrol Agents. Frontiers in Microbiology, 12.

[6] Campus, S., 2022. Tackle fungal forces to save crops, forests and endangered animals, say scientists | Imperial News | Imperial College London. [online] Imperial News. Available at: https://www.imperial.ac.uk/news/108986/tackle-fungal-forces-save-crops-forests [Accessed 13 October 2022].

[7] Moore, D., Robson, G., & Trinci, A. (2020). 21st Century Guidebook to Fungi (2nd ed.). Cambridge: Cambridge University Press. doi:10.1017/9781108776387.

[8] Prank, M. et al. (2019) ‘Climate change impacts the spread potential of wheat stem rust, a significant crop disease’, Environmental Research Letters, 14(12), p. 124053. doi:10.1088/1748-9326/ab57de.

[9] Fones, H.N. et al. (2020) ‘Threats to global food security from emerging fungal and oomycete crop pathogens’, Nature Food, 1(6), pp. 332–342. Available at: https://doi.org/10.1038/s43016-020-0075-0.

[10] Managing stem rust of wheat (no date). Available at: https://www.agric.wa.gov.au/grains-research-development/managing-stem-rust-wheat?nopaging=1 (Accessed: 6 June 2022).

[11] Steinberg, G., & Gurr, S. J. (2020). Fungi, fungicide discovery and global food security. Fungal genetics and biology : FG & B, 144, 103476. https://doi.org/10.1016/j.fgb.2020.103476.

[12] Shafi, J., Tian, H. and Ji, M. (2017) ‘Bacillus species as versatile weapons for plant pathogens: a review’, Biotechnology & Biotechnological Equipment, 31(3), pp. 446–459. doi:10.1080/13102818.2017.1286950.

[13] Donley, A. (2021) From the editor: India’s agriculture conundrum, World Grain. Available at: https://www.world-grain.com/articles/15421-from-the-editor-indias-agriculture-conundrum (Accessed: 6 June 2022).

[14] Figueroa, M., Hammond‐Kosack, K.E. and Solomon, P.S. (2017) ‘A review of wheat diseases—a field perspective’, Molecular Plant Pathology, 19(6), pp. 1523–1536. doi:10.1111/mpp.12618.

[15] Working to End Hunger, Now and in the Future (no date) World Bank. Available at: https://www.worldbank.org/en/news/feature/2014/10/16/working-to-end-hunger-now-and-in-the-future (Accessed: 6 June 2022).

[16] Joint Statement: The Heads of the World Bank Group, IMF, WFP, and WTO Call for Urgent Coordinated Action on Food Security (no date a) World Bank. Available at: https://www.worldbank.org/en/news/statement/2022/04/13 joint-statement-the-heads-of-the-world-bank-group-imf-wfp-and-wto-call-for-urgent-coordinated-action-on-food-security (Accessed: 6 June 2022).

[17] Choudhary, P. et al. (2018) ‘Harmful effects of fungicides: current status.’

[18] Sarkar, S. et al. (January 2021) ‘The use of pesticides in developing countries and their impact on health and the right to food’, p. 56.

[19] Shafi, J., Tian, H. and Ji, M. (2017) ‘Bacillus species as versatile weapons for plant pathogens: a review’, Biotechnology & Biotechnological Equipment, 31(3), pp. 446–459. doi:10.1080/13102818.2017.1286950.