Leveraging Industry-Academia Collaborations in Adaptive Biomedical Innovation.

Despite the rapid pace of biomedical innovation, research and development (R&D) productivity in the pharmaceutical industry has not improved broadly. Increasingly, firms need to leverage new approaches to product development and commercial execution, while maintaining adaptability to rapid changes in the marketplace and in biomedical science. Firms are also seeking ways to capture some of the talent, infrastructure, and innovation that depends on federal R&D investment. As a result, a major transition to external innovation is taking place across the industry. One example of these external innovation initiatives is the Sanofi-MIT Partnership, which provided seed funding to MIT investigators to develop novel solutions and approaches in areas of interest to Sanofi. These projects were highly collaborative, with information and materials flowing both ways. The relatively small amount of funding and short time frame of the awards built an adaptable and flexible process to advance translational science.

Cytochrome b562 variants: a library for examining redox potential evolution.

A general understanding of how cytochromes evolve within a fixed structure to optimize redox potential for specific bioenergetic processes does not exist. Toward this end, a library approach is used to investigate the range and distribution of redox potential which occurs when all sequence space available through mutation at two positions is examined within a fixed structural motif. Random mutation of Phe61 and Phe65 of cytochrome b562 (E. coli), and subsequent examination of a statistically significant sampling of this library, demonstrates that the redox potential can vary over 100 mV (>25% of the known accessible potential in native proteins with axial His-Met ligation) through mutation at these two positions. The redox potential of the wild-type protein occurs at an extremum of the distribution observed, indicating that Phe61 and Phe65 were most likely naturally selected to differentially stabilize the reduced state of the protein. At the other extremum, a compositionally conservative set of mutations (F61I, F65Y) leads to a 100 mV shift in the redox equilibrium toward the oxidized state. NMR analyses indicate that a charge-dipole interaction which results from mutation of phenylalanine to tyrosine at position 65 may be responsible.