Grant: Discovery Development Grant

Plants remain a significant source of bioactive compounds, despite advances in synthetic and combinational chemistry, with >70% of new chemical entities developed between 1981 and 2010 derived from natural products. These include synthetic mimics, semi-synthetic compounds derived from natural products and structural analogs. The chemical complexity within individual plant species is immense; yet the diversity of chemical compounds within the plant kingdom can be further enhanced through inter-specific hybridization of plants. Chemical compounds produced by hybrid plants may be: (1) similar to that of their parents, (2) intermediate between those of the their parents, (3) expressed in different concentrations than in the parents, (4) absent, in that the hybrids do not express the chemicals found in either parents, or (5) novel, in that the hybrids express chemicals not found in either parents. Such changes in chemical profiles could serve as an excellent source for the production, development and/or discovery of bioactive compounds. Discovering new bioactive compounds in the secondary metabolite chemistry of plants requires an analytical approach to detect and interpret a large number of chemical signals within each plant sample. Advances in chromatography, spectrometric technologies and approaches have enabled researchers to acquire significant, high-dimensional and complicated data sets making such investigations possible. However, there is a significant debate about the design of such experiments, there is a lack of suitable standards and the data analysis is not fully developed. I propose to develop statistical tools that allow for interpretation, prioritization and evaluation of data to effectively eliminate false discoveries and identify bioactive compounds.. The proposed research will undertake metabolomic studies to investigate the chemistry of parent and hybrid plant specimens and related species using Artemesia annua as the selected model system. A. annua is a rich source of bioactive compounds including the highly effective anti-malarial compound artemisinin. Metabolomics with univariate and multivariate analyses to examine the production and development of bioactive compounds within plants, the impact of breeding on biosynthetic pathways and ultimately a means through which novel compounds can be discovered will be investigated. Further this study should also allow for the development of a better understanding of the biosynthesis of the major active constituents with A. annua and the factors that can influence biosynthetic processes in plant selection and breeding for improved crop production.