Bowie, James U.

Biography

Research Interests

As of 2024, Bowie’s work had been cited nearly 30,000 times with an H-index of 76

-Bowie invented the field of “Fold Recognition” as a postdoc with David Eisenberg. Fold recognition is a structure prediction technique that evaluates how well a protein sequence fits with an already known structure.  The original publications have been cited thousands of times.

-Bowie pioneered studies in membrane protein folding. Folding studies with membrane proteins are particularly challenging because they reside in a complex, non-homogenous environment.  To drive unfolding of membrane proteins, Bowie developed a number of novel approaches:  first he used denaturing detergents, and then he invented a “steric trapping” approach to stabilize proteins in the unfolded state. Finally, in collaboration with the Tae-Young Yoon laboratory, he employed single molecule forced unfolding methods.  These techniques allowed Bowie to investigate the energetics and folding pathways of helical membrane proteins, ultimately demonstrating the co-translational folding model in which helical membrane proteins can fold as they enter the membrane.

-Bowie discovered that Sterile-Alpha-Motif (SAM) domains can polymerize. SAM domains are among the most common protein modules in eukaryotic cells.  Bowie discovered that SAM domains can form polymers, thereby enabling diverse proteins to form large assemblies.  Bowie showed how SAM domains can contribute to the creation of large protein complexes at neural synapses, how they create transcriptionally repressed chromatin domains, how assembly can be regulated, and how mutations in SAM domain lead to disease.

-Bowie pioneered “synthetic biochemistry” for industrial chemical production. Biomanufacturing had traditionally envisioned introducing enzyme pathways into cells so that they produce the chemicals that we desire. Yet biomanufacturing using engineered microbes suffers from often insurmountable challenges including low yields, low titers, or expensive product isolation.  These challenges are particularly problematic for low-value products like biofuels where cost is critical.  Bowie developed an alternative approach in which the pathway enzymes are housed in a bioreactor rather than within cells.  Bowie developed methods to build robust enzyme systems, much more complex than previously thought possible for industrial chemical production.  In 2019 Bowie co-founded a company, Invizyne Technologies, to develop chemical manufacturing using these enzyme systems, thereby providing environmentally friendly chemical production processes.