Ph.d.-forsvar - Madeleine Ernst – Københavns Universitet

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Ph.d.-forsvar - Madeleine Ernst

Evolutionary approaches to plant-based drug discovery have suggested that phylogeny can guide the search for new plant-derived drugs, in particular by systematizing species selection. The genus Euphorbia is among the largest genera of flowering plants with an almost cosmopolitan distribution. Its species richness and remarkable diversity in growth forms have made it a model group for understanding plant evolution and diversification. Also, Euphorbia species produce an often chemically highly diverse latex exhibiting an exceptional number of biological activities with pharmaceutical interest. In this PhD project, the genus Euphorbia was chosen as a model group for studying evolutionary approaches to plant-based drug discovery. Phylogenetic patterns in species used in traditional medicine were investigated, and it was found that species used medicinally are not randomly distributed across the phylogenetic tree. Subsequently, Euphorbia chemical diversity and bioactivity were investigated using mass spectral molecular networking, 3D mass spectral imaging as well as high-resolution bioactivity profiling in cell-based highthroughput screening assays of a genus-wide representative subset of over 40 species sampled from the Botanical Garden in Copenhagen. More than 600 specialized metabolites could be putatively identified, and for the first time, their genus-wide distribution, as well as evolutionary drivers of the chemical diversity in Euphorbia, could be assessed. The pharmaceutically highly relevant Euphorbia diterpenoids were found to be structurally most diverse in species native to Europe, Africa, and Asia compared to species native to the Americas. It is hypothesized that these species are subject to a coevolutionary plant-herbivore arms race, leading to more diverse and biologically active molecules.

Supervisor

Professor Nina Rønsted (Natural History Museum, Denmark)

Co-supervisors

Associate Professor Henrik Toft Simonsen (Technical University of Denmark)
Head of Section Niclas Nilsson (LEO Pharma A/S, Denmark)
Research Leader Olwen M. Grace (Royal Botanic Gardens, KEW, UK)

Assessment Committee

Associate Professor Enrico Cappellini (Natural History Museum, Denmark) – chairman
Professor Jean-Luc Wolfender (University of Geneva, Switzerland)
Director and Professor Nyree J. C. Zerega (Northwestern University and the Chicago Botanic Garden, USA)