ChBE Seminar Series Ganesh Sriram
Friday, October 11, 2013
10:00 a.m.-11:00 a.m.
Room 2108, Chemical and Nuclear Enginering Bldg.
Professor Jeffery Klauda
Investigations of Chemical Traffic in Cells Toward Hypothesis-Driven Metabolic Engineering
Dept. of Chemical and Biomolecular Engineering
University of Maryland
Like chemical process plants, living cells perform numerous reaction and transport processes collectively known as metabolism. However, the metabolic potential of even unicellular organisms remains complex and incompletely charted. Detailed investigations of cellular metabolism are crucial to fundamentally understanding cellular behavior, assessing how cells respond to environmental or genetic perturbations as well as engineering cells for improved performance. Systems biology tools such as isotope labeling, metabolic flux analysis and flux balance analysis enable quantitative dissection of carbon traffic in metabolism. This presentation will discuss the development of computational and experimental tools in this area as well as their application to three variegated cellular systems. First, we will discuss carbon concentration in an algal system (the diatom Phaeodactylum tricornutum). Diatoms are postulated to be photosynthetically efficient, but the molecular mechanisms underlying this efficiency are barely known. This presentation will discuss isotope labeling experiments and modeling that elucidated a carbon-concentrating mechanism in P. tricornutum. Next, we will discuss how our tools can be applied to design metabolic engineering strategies to enable yeast cells to synthesize an antimalarial therapeutic. Finally, we will discuss our work on carbon-nitrogen interactions in a plant system (poplar cell suspensions). To study how cells respond to low supply of nitrogen (an expensive element for plants), we designed and performed parallel labeling experiments utilizing a number of isotopically labeled forms of glucose on the cell suspensions. These experiments pointed to mechanisms by which poplar cells maximize nitrogen use efficiency under conditions of limited nitrogen availability. The presentation will conclude with a short summary of our ongoing and future work in the areas of metabolic engineering and systems biology.