With support from the Chemical Measurement and Imaging Program in the Division of Chemistry, Professor Sarah Rutan at Virginia Commonwealth University, Professor Peter Carr at University of Minnesota, Professor Dwight Stoll at Gustavus Adolphus College and their groups will address the challenges of performing quantitative comprehensive two dimensional liquid chromatography (LCxLC). This technique carries out separations of the component molecules present in complex mixtures using two very different liquid separation systems, and offers a more powerful method for separating complex mixtures such as urine. The proposed research will enable LCxLC to become a practical technique for the analysis of small molecule metabolites, which will therefore lead to more rapid and facile discovery of molecular markers of disease and treatment. The intellectual merit of the work carried out by this team of investigators lies in the development of a fundamental understanding of how changes in the chemistry of the chromatographic separation processes affect the characteristics of the resulting data, developing an understanding how these chemical factors affect the performance of the data analysis methods, and tuning the data analysis methods to adapt to these data features. These efforts will transform a time-consuming process that is at best semi-quantitative, into a rapid and efficient method that will provide precise, quantitative results for biomarker identification.
The broader impacts of the work lie in providing biological scientists with the tools needed to characterize the amounts and relationships of various molecular players as they vary depending on growth, disease state and environmental exposure. This research will contribute towards reaching a holistic understanding of complex biological systems. This knowledge will contribute to refined technologies that have tremendous promise for understanding and curing diseases, enhancing agriculture and preserving the environment. In order to make chromatographic concepts more accessible to students, a series of dynamic, online homework problems will be developed based on online LC simulators. There is also a strong component of human resources development in the training of graduate and undergraduate students, and post-doctoral scholars for careers in chemistry and biology. The students working on this project will benefit from the synergy of working with three talented and creative researchers in separation science.
