Applications of Protein and Metabolic Engineering to Health and Disease

 

Scott Banta, Ph.D.

Center for Engineering in Medicine

Harvard Medical School

 

Recently, there has been a great deal of interest in the concept of "Systems Biology" where an attempt is made to understand an entire biological system, from structure, to dynamic interactions, to levels of control, instead of simply studying its component parts in isolation.  A similar approach can be taken in the fields of Protein and Metabolic Engineering.  Protein Engineering provides a powerful set of tools to design, construct and evaluate new proteins with novel functions and properties.  However, the true value of such advances requires a "Systems" approach that can be provided by Metabolic Engineering, through its ability to characterize metabolic pathways composed of a constellation of different enzymes. 

In this talk, a recent research project using Protein Engineering to improve the biological production of Vitamin C will be discussed.  This work led to the creation of a novel enzyme with altered cofactor specificity, and through careful mathematical modeling, it appears that this new enzyme should produce a substantial cost savings in the industrial production of Vitamin C.

This will be followed by the discussion of ongoing research using Metabolic Engineering to investigate the body's response to burn injury or other trauma.  Perfused organ models coupled with Metabolic Flux Analysis have been used to quantitatively characterize these systemic responses, as well as the effects of interventions aimed at diminishing these responses, in both the liver and the skeletal muscle.  In the final example, hepatic metabolic flux results obtained following a severe insult are compared to gene expression results obtained from a DNA microarray analysis.  By combining these orthogonal approaches, an improved understanding of the metabolic consequences of a diseased state can be elucidated.

 Finally, the talk will conclude with an example of a future research project that combines the fields of Protein and Metabolic Engineering, in an attempt to advance a new therapy for the treatment of Parkinson's disease.