PITA Fiscal Year 2007 Projects

Biomedical and Health Engineering

Development and Demonstration of Metabolica for Computational Support of Metabolic Engineering
Work will be pursued that yields a fully integrated computational tool called Metabologica. The tool will augment the ability to perform tasks that are central to many biotech/pharma businesses. First, cellular metabolic reaction networks can be analyzed to determine feasible and optimal “traffic flows” that result in the direction of cellular resources into the maximal production of biotechnological products such as insulin. The optimal flows provided by Metabologica are useful because they guide the re-engineering of cells that aims to increase the amount of product obtained from cell-based commercial processes. Alternately, the effects of mutations or drugs on the “metabolically whole cell” can be predicted, which supports the design of new drugs or interpreting better the genetic origin of diseases and their associated metabolic manifestations. The second task that will be enabled by Metabologica is the design of “tracer experiments” that provide information on what the individual metabolic “traffic flows” actually are within normal, engineered, or diseased cells or tissues. Metabologica will allow for the design of tracer experiments that generate unambiguous results, which will improve cell engineering, diagnostics, and/or strengthen biotechnology/pharma patent claims.

To demonstrate Metabolica’s capabilities, experimental applications will also be pursued. For example, the basis for why using the renewable feedstock glycerol in bacterial industrial fermentations results in nil toxic by-products and higher protein product yields will be fathomed. Apart from the positive biotechnological impact, using glycerol in a biotech process could also favorably impact the development of biodiesel in PA because glycerol is a major by-product in biodiesel manufacture. Thus, one renewable resource (e.g. soy beans) could “feed” both the energy (diesel esters) and medicinal (glycerol-derived biotech/pharma products) industries and economies. Additionally, Metabologica will be introduced into a chemical engineering lab course to assess its educational potential through another application: the bioconversion of corn starch into a monomer that is used to synthesize a commercial polymer. Producing the polymer using, in part, using renewable resources in envisioned to lower the demand for oil-derived chemicals. Students will use the tool to analyze their data and assess whether productivity enhancements can be made based on the network analysis results.