Research Program

Current Projects

Research Methods

Microflow Bioreactors to Study Solvent Tolerance

Ph.D. Student: Aditi Swarup
Undergraduate Students: Michelle Betty, Josh Bender, and Kevin Campbell

Dynamic Metabolic Flux Analysis Microflow Bioreactors

This research project deals with the study and manipulation of microbial cells for the production of sustainable energy sources (or biofuels), the importance of which has been recognized worldwide and is rapidly gaining in significance. To achieve this goal new microbial strains have to be engineered that are tolerant to high levels of ethanol, butanol and other products of biomass. Until now, metabolic engineering techniques have achieved small increases in tolerance to ethanol and other compounds. This is partly explained by our limited understanding of cellular mechanisms responsible for eliciting complex phenotypes such as tolerance to toxic compounds. Genomic and transcriptomic methods were used to study cellular responses to increased solvent levels; however, these systems are still poorly characterized at the relevant metabolic and reaction flux level.

The goal of this project is to use a systems biology approach to elucidate the solvent tolerance phonotype in two model microorganisms, E. coli and S. cerevisiae. We will use mini-scale chemostats and 13C metabolic flux analysis technology to characterize metabolic flux distributions and metabolite profiles under controlled experimental conditions such as high/medium/low levels of ethanol and butanol, and at varying growth rates. Flux measurements will then be integrated with other genome-wide data (e.g. DNA microarrays) using a systems biology approach to provide a global perspective on the integrated genetic and metabolic regulations that occur within cells. The results will provide valuable information for rational strain design and target selection.



References

Young JD, Walther JL, Antoniewicz MR, Yoo H, Stephanopoulos G.
An Elementary Metabolite Unit (EMU) based method of isotopically nonstationary flux analysis. Biotechnol Bioeng, 2007


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