Project ESR3: Domesticating deadly carrots. Predicting the biosynthetic pathway of Thapsigargins for the treatment of solid tumours

PhD-fellow: Karen Martinez

Supervision: Dr. Henrik Toft Simonsen

Host Institution: Department of Plant and Environmental Sciences, University of Copenhagen.

Co-supervisors: Dr. Nina Rønsted, Natural History Museum of Denmark, University of Copenhagen; Dorian Marban, ThapsIbiza (AC1); Gary Martin, Global Diversity Foundation (AC2).

This project will use phylogeny and chemical profiles to revise the genus Thapsia and define the species and identify high-level of thapsigargin producing varieties. Seasonal and geographical variation of expression of biosynthetic genes will be studied and new genes involved in biosynthesis of thapsigargin may be identified.

About the project

Thapsigargin is the active component of a pro‐drug currently being developed for the treatment of solid tumours. The Thapsigargin compound can only be isolated from members of the genus Thapsia L. found in the Mediterranean. However, the genus is taxonomic mess, with over 40 synonyms and species frequently misidentified. In addition, Thapsia species do not grow well out of their natural habitat and so the manufacture of this new pro-drug could potentially encounter a resource problem. With this project we hope to firstly make a complete revision of the genus. Secondly, we aim to study how Thapsigargin is synthesised within the plant (its biosynthetic pathway). Finally we hope to establish the biochemical activity of predicted enzymes in this pathway to pave the way for biotechnological products and also to find a marker for the future selection of plants.

Duration: 3 years – start March 15th 2014.