Professor Ian A Graham FRS

Research

Ian Graham’s interests include how plants make and breakdown various metabolites, how these processes are controlled and how they impact on plant growth. He has used biochemical genetics to dissect the main metabolic pathways controlling oil mobilisation in Arabidopsis seed (Graham, 2008). Similar approaches were used to understand and modify fatty acid composition of industrial hemp oilseeds (Bielecka et al 2014), resulting in UK registration in 2021 of CNAP1HOH as a dual purpose, high oleic acid variety that produces seed and biomass (shiv and fibre). The novel high oleic acid seed oil trait is five times more stable than conventional hemp seed oil at 20°C, offering new functionality and opportunity to the food processing industry. 

The Graham lab also works on the genetic improvement of some of the world’s major medicinal crops. Characterisation and genetic mapping of traits responsible for production of the 15-carbon sesquiterpene artemisinin in Artemisia annua (Graham et al., 2010) has enabled development of F1 hybrid seed that can deliver a robust source of this vital anti-malarial drug for the developing world. Molecular genetic dissection of the key steps in artemisinin production has revealed new insight into the flexibility of sesquiterpene metabolism in glandular secretory trichomes (Czechowski et al., 2016) and genome assembly provides new knowledge and tools for improved production of artemisinin (Liao et al., 2022).

The 20-carbon diterpenoids represent another major terpenoid class with proven functionality across a range of industrial sectors. The Graham lab has led on the elucidation of the casbene-derived diterpenoid biosynthetic pathway from Euphorbiaceae species with discovery of the jolkinol C (lathyrane) biosynthetic gene cluster (King et al., 2014; King et al, 2016) opening up new opportunities to extend the pathway engineering to bioactive jatrophanes, ingenanes, tiglianes (phorbol esters) and other polycyclic diterpenoids. Development of Euphorbia peplus as a model species for biochemical genetic elucidation of casbene derived jatrophane and ingenane biosynthesis is providing new insight and gene tools for engineering the production of important medicinal compounds in heterologous hosts (Czechowski et al., 2022).

Another very important class of plant natural products are the alkaloids. The discovery in the Graham lab of a 10 gene cluster responsible for the production of the anti-tussive alkaloid compound noscapine in opium poppy provided the tools for molecular breeding of new commercial varieties (Winzer et al., 2012). The discovery of a novel P450 – oxidoreductase gene fusion described the last unknown step in synthesis of morphine and codeine (Winzer et al., 2015) and the first assembly of the opium poppy genome provided new insight into the evolution of morphinan production in this important medicinal crop (Guo et al., 2018). Evolutionary analysis of related Papaver species has identified when key events resulting in production of morphinans occurred and also uncovered novel related molecules (Catania et al., 2022).

Current projects

• Molecular breeding of a commercial pharmaceutical crop
  Funding body: Sun Pharmaceutical Industries Pty Ltd

• Centre for High Carbon Capture Cropping (CHCx3)
  Funding body: Defra, in partnership with Innovate UK

• High Value Biorenewables (HVB) network
  Funding body: UKRI BBSRC

• Bioactive terpenoids as high performance ingredients for industry
  Funding body: UKRI BBSRC Prosperity Partnership Award with Croda