[Disclosure: AgFunderNews’ parent company AgFunder is an investor in Resurrect Bio]
In the evolutionary arms race between plants and pathogens, the pathogens often find a way around the plant’s defenses. Resurrect Bio has a novel, chemical-free approach to help crops fight back.
Rather than importing resistance genes from wild relatives or knocking out genes that make crops susceptible to disease, UK-based Resurrect Bio uses AI to map interactions between plant immune receptors and proteins deployed by pathogens and pests to suppress or evade an immune response.
It can then pinpoint precisely where partners at seed companies can make gene edits in the plant to disrupt those interactions, effectively locking pathogens out and allowing plants to defend themselves again.
The approach could enable crops to fight off threats including fungi, oomycetes and nematodes without the need for chemical crop inputs, an appealing proposition as farmers seek to reduce pesticide use and grapple with rising resistance to existing chemistries.
AgFunderNews (AFN) caught up with cofounder and CEO Cian Duggan (CD) at the World Agri-Tech innovation summit in London to discuss the firm’s FloraFold platform, the durability of disease resistance, and how to stay one step ahead of plant pests.
AFN: In a nutshell, what does Resurrect Bio do?
CD: We’re finding the resistance genes, the immune receptors that are naturally occurring in plants and crops, which have been defeated by pathogens and pests through evolution.
We’re discovering those, and we’re engineering or designing edits which will resurrect and restore their function, so the plant can defend itself again.
AFN: In practice, what does this involve?
CD: In many cases, we’re looking for what we call suppressors. These are proteins from pathogens or pests that are secreted inside plant cells, and they often directly bind plant immune receptors, and they block the function of that immune receptor and stop the immune system doing its job.
The other way that it can happen is that pathogen proteins are doing something else in the cell. They’re trying to subvert the cell in some other way, and the plant has evolved a way of detecting it. But then the pathogen escapes that recognition, and we’re re-establishing that recognition.
So it can be both a positive and a negative thing that we’re trying to achieve. We’re trying to either break an interaction or fix an interaction.
AFN: Where does AI come in?
CD: We start with our FloraFold AI platform, which is a protein folding tool. It enables us to try to predict protein-protein interactions, so we can scale that really nicely. The name comes from Google Deepmind’s AlphaFold [protein structure database], but it’s tailored towards plants, plant pathogens, and plant pests.
It’s quite a niche use case, but a very important use case. It’s really there to reduce the search space because there are so many plant immune receptors and pathogen proteins. We’re trying to reduce the search space so that our wet lab, which is the majority of our work, has to screen fewer things.
Then the third step in our process is the resurrection step. So that is protein engineering. We’re designing the smallest number of DNA changes possible to either break that suppression interaction or enable the redetection of a pathogen, and we license those [genome] edits to seed companies or plant breeders.
AFN: If you start trying to resurrect a plant’s natural immunity, are there any downsides/tradeoffs?
CD: Anything you do to a plant can have downsides and upsides. Conventional breeding has that, and it can have many negative effects. So they select for the rare positive ones. But actually, our technology is so specific to these resistance genes, these resistance proteins.
We screen out negative effects very early on, so by the time it gets to the breeder’s hands, the chances of any unwanted effects are extremely low. Probably the lowest out of any technology out there for this, and ultimately it’s fundamentally determined by field trials.
AFN: Can your basic approach be applied to any crop/pest interaction?
CD: So Resurrect Bio can work on any crop, most pathogens, and many pests. We’re designing a trait against potato blight or against a virus. It’s usually species specific; it’s not a one-size-fits-all. We don’t just design one trait like Bt, for instance, and put it into multiple crops. But rather, it’s a very targeted approach, almost like personalized medicine.
We usually choose a crop and a pathogen, and we develop a trait specifically for that. But a similar trait would work in other crops as well. So the technology really works across many crops. At the moment, for instance, we’re working on potato and tomato, which are very closely related, but we’re also working on soy and corn, which are completely unrelated plants, and even spinach, so we’re really not limited to any particular crop.
The only decision to make there is really a commercial one rather than a technical one.
AFN: Plants and pathogens are in this constant evolutionary arms race. Is resistance created using your approach any more durable than any other approach?
CD: It can be. The main thing, and something my cofounders—who are world-class academics in this area—like to say, is never bet against the pathogen. The pathogen will always win eventually, and that’s what we expect. It’s natural. We’re okay with that. It’s an arms race, and we’re just one step [ahead] in the arms race.
But the good news is now, thanks to technologies like ours and particularly AI, it does give us a leading edge to be able to try to predict what the pathogen is going to do next. And because we know the mode of action of how they’ve overcome these resistance issues before, we can do a pretty good job of predicting what they’ll do next. So we can try to stay one step ahead!
AFN: How does Resurrect Bio’s approach compare to others designed to build disease resistance?
CD: A lot of companies won’t have a platform. They’ll be looking at the literature and trying to find something from an academic lab. Many will look for wild resistance genes and introgress them. It’s quite time consuming, and often by the time you get it into the crop, there’s already a pathogen isolate that’s overcoming it because they’ve already evolved together.
And the other one is what’s known as loss of susceptibility. That’s finding basically a gene in a plant that is allowing the pathogen in, I call it a back door to the plant, and they knock that out.
That can be quite durable, and it can be quite broad spectrum. But the downside for me is that the back doors in buildings often have a function. They’re often escape routes, right? Fire doors. So maybe by the time you get it out to the field, in a few years, a drought comes and it dies from drought and you didn’t realize.
So I prefer to go for resistance genes because that is naturally how plants defend themselves. They don’t defend themselves with susceptibility genes.
AFN: How do you work with potential partners?
CD: We have basically two ways of working together. One is we develop traits internally and then we out license those, and that’s usually for small upfront milestone payments, but ultimately with value sharing in the long run.
And the other way is that partners can sponsor a project from day one, and this is a really excellent way for them to get us working on something that they really care about, and it guarantees access for them of that trait at the end.
AFN: Europe has now moved forward on its new genomic techniques framework, so you’ve got a more streamlined pathway for gene edited crops. How significant is that for your business?
CD: So when Resurrect Bio started five years ago, we knew eventually the EU would adopt new regulations, but we didn’t hold our breath because you never know what’s going to happen, especially with complex bureaucracies like the EU.
So we really focused on the Americas for our product development, always keeping in the back of our mind that one day our home turf would have regulations available. And thankfully the UK came first, and more recently, and really excitingly, because it’s a large market, the EU. So we’re really excited to produce products for all of these geographies.
AFN: What is your focus for the next 12 to 18 months?
CD: We closed our Series A about six months ago, and we’ve been building our team and our capacity and capabilities for product development.
So now we’re really focused on executing on that product development. We’re working on soy, corn, tomato, potato, and spinach, and we’re working across several pathogens and pests in those crops. We’re focusing on those and also establishing partnerships with some big names and some smaller names as well.
Further reading:
Exclusive: Plantik and Hudson River Biotechnology team up to de-risk heat-tolerant strawberries
‘Bring us your difficult trait problems’: Biographica, Hudson River partner on crop genome editing
Pairwise sees ‘dramatic uptick’ in CRISPR licensing as gene editing moves beyond row crops
Upstream Biotechnology raises seed funding for ‘on-demand’ crop defense tech
