Cell biology of plant natural products

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The long-term goal of my research is to understand the biosynthesis, transport, and storage of plant natural products (secondary metabolites). Plants are an important resource for a vast array of chemicals that serve us in industrial and health-related applications. Over 11% of the 252 drugs identified as essential by the World Health Organization are from higher plants; more still are synthetic derivatives obtained from natural precursors. Many industrial applications rely on plant-derived oils and waxes, such as Jojoba (Simmondsia chinensis) wax esters which are used as a lubricant in high-pressure applications such as automobile transmissions. The biosynthesis of health-related and economically important plant natural products is an active area of research, however less is known about the cellular aspects of biosynthesis. Often, the site of accumulation of a secondary metabolite is physically separated from the site of biosynthesis; many of these compounds are toxic to the cell and must be carefully stored. An understanding of the localization and transport of natural products will be essential for bioengineering of secondary metabolic pathways in plants. I am studying two model systems: wax secretion in Arabidopsis thaliana and artemisinin biosynthesis and transport in Artemisia annua. The waxy cuticle is a protective layer protecting the plant from pathogens and drought; and understanding of the cuticle is very important for agriculture. Artemisia annua is the source of artemisinin, an important anti-malarial drug, but the rising cost of production is making this drug difficult to obtain for many in the developing world, where it is most needed. Towards this understanding, the initial focus of my research will be on ATP-binding cassette (ABC) transporters, which have been shown to play a key role in the transport and sequestration of many different secondary metabolites in many species. Characterization of these ABC transporters will be useful for producing pest and/or drought-resistant crops; improving artemisinin production through crop improvement or bioengineering applications. Moreover, understanding transport in these systems will provide clues to understanding the cell biology of plant natural products in general.