CAREER: A novel approach for deciphering cellular metabolic phenotypes using tandem mass spectrometry

University Of Delaware, Newark DE

Investigators

Abstract

The overall research objective of this proposal is to develop better understanding of cellular metabolism to allow purposeful manipulation of cell behavior. Metabolism is the fundamental process by which living cells convert nutrients into products. The current state-of-knowledge regarding the role of metabolism in cellular behavior is limited due to difficulties in measuring intracellular metabolic fluxes precisely and accurately. This project will contribute to the knowledge of microbial metabolism and cell physiology by quantifying the metabolic state of cells at a much higher level of precision and accuracy using a novel measurement technique, tandem mass spectrometry. The proposed work will add to the scientific understanding by: (1) introducing a new method of metabolic flux analysis (MFA); (2) providing improved techniques for validating flux results and identifying potential sources of errors; (3) developing new algorithms and easy to use tools for MFA; and (4) improving knowledge of metabolic network operation for two important model microbes, Escherichia coli and Saccharomyces cerevisiae. The educational objective of this proposal is to promote teaching of quantitative systems biology principles as an integral part of chemical engineering education and to enhance the participation of underrepresented groups in biological research. Specifically, the educational approach is to: (1) provide summer research opportunities to minority undergraduate students from Delaware State University, a local premier HBCU; and (2) develop new course material and a stimulating capstone laboratory course on biological protein production, recovery and purification at the University of Delaware. This project also provides unique opportunities for student education and training in an interdisciplinary environment. Students will gain experience in microbial cell culture, metabolic engineering, metabolomics, flux analysis, mass spectrometry and quantitative modeling. These experiences will place the students at the forefront of metabolic engineering and the emerging field of quantitative systems biotechnology.