By Ashley Stender | October 2, 2026

“We’re still at the tip of the iceberg of opportunity around natural products,” Ian Graham says.

Graham is the Weston Chair of Biochemical Genetics and a professor in the Centre for Novel Agricultural Products (CNAP) at the University of York. His research uses genetics to uncover how plants produce compounds with important biological effects.

Using Genetics to Unlock Plant Chemistry

Graham’s interest in plant genetics began long before C-SPIRIT. Coming from a farming background, he was drawn early to plants and crops, studying botany and genetics before becoming increasingly interested in the chemistry behind the compounds plants produce.

“Genetics is really the first love of my life when it comes to addressing some of these big scientific questions in plant biology,” Graham says. “Not only does it help you to discover genes, but it really gives you an understanding of what those genes are doing.”

When a plant produces an unusual compound or trait – in response to pests, for example – genetics can help researchers identify the genes responsible. Graham’s lab has used this approach across a wide range of plants, including the model species Arabidopsis, opium poppy, Artemisia annua, and E. peplus.

By combining genetics with genome sequencing, the team can connect a plant’s chemistry to the genes and enzymes behind it. In E. peplus, the plant’s apparent resistance to insect feeding gives the team a particularly useful trait to investigate.

A Small Plant with a Powerful Chemical Arsenal

The plant is also well suited to genetic research. Its relatively small genome gives researchers less DNA to search when looking for a genetic change behind an interesting trait. The team can also create mutations or reduce the activity of individual genes to test how each one affects the plant’s chemistry.

Feeding experiments have shown why that chemistry matters. Graham describes insects rapidly stripping the leaves from plants carrying a mutation, while plants without the mutation were “just sitting there smiling with these delicious, luscious leaves that haven’t been touched.”

The contrast supports the team’s focus on jatrophanes as part of the plant’s defense against herbivores. It also raises a larger question: Could that defense eventually help protect agricultural crops?

From Pathway Discovery to Production

Through C-SPIRIT’s Aim 3, focused on gene and pathway discovery, the Graham Lab is identifying the genes and enzymes involved in jatrophane biosynthesis, the sequence of biological reactions the plant uses to make the compounds. Graham says the team has narrowed a key part of the pathway to one remaining gene, which they believe could help reveal how the core structure of jatrophanes is formed. 

Once researchers know those biological instructions, the challenge shifts from discovery to production. That connects the work with Aim 4, which focuses on producing promising compounds using biological systems.

“Euphorbia peplus is a weed, and you’re never going to grow it commercially on a farm,” Graham says. “So you have to think, ‘It makes these amazing chemicals. How can we then produce these chemicals somewhere else?’”

One possible answer is to transfer the necessary genes into organisms such as yeast or bacteria, enabling them to produce the compounds through fermentation. For structurally complex natural products such as jatrophanes, this biological route may be more practical than building the molecules through conventional chemical synthesis.

Producing the compounds, however, would not establish whether they are effective or safe enough for agricultural use.

Testing the Agricultural Potential

The Graham Lab has provided diterpenoid compounds to other C-SPIRIT researchers for testing against fungi that cause plant disease. The work is exploring whether compounds associated with defense against herbivores may also act against fungi.

The team is also testing jatrophanes against cabbage moth larvae, a broad-feeding agricultural pest that affects several C-SPIRIT crops. Graham hopes promising compounds can eventually move into initial field trials and more extensive toxicity testing.

That safety work is essential because a compound’s natural origin does not automatically make it harmless.

“Just because a compound is a natural product, it doesn’t mean that it can’t be toxic,” Graham says. “They’ve evolved to be toxic, and so we have to consider all of those aspects as well.”

Together, laboratory, field and safety studies can show whether the compounds have the effectiveness, safety and production potential needed to move responsibly toward agricultural use.

Building a Path Beyond C-SPIRIT

For Graham, proof of concept would mean showing that the jatrophane pathway can be understood, the compounds can be produced, and their effects and safety can be tested.

That evidence would mark a beginning rather than an endpoint. It could give future researchers, industry partners or investors a foundation for larger-scale production, broader testing, regulatory assessment and, potentially, the development of agricultural products.

Graham hopes the results will be strong enough for someone to “take this and run with it” by investing in the next stage.

A chemical defense found in a small weed may seem far removed from protecting crops in farmers’ fields. By uncovering how that defense works and developing ways to produce and test its compounds, the Graham Lab is helping close that distance. If successful, the work could extend well beyond C-SPIRIT, contributing new biologically based options for crop protection and expanding the tools available for more sustainable agriculture.