Dr. David W. Wood
Ohio State University
Chemical & Biomolecular Engineering
Friday-March 22, 2013
New Technologies from Engineered Self-Modifying Proteins
Professor Wood’s work seeks to apply biological concepts of protein function, cell metabolism, genetics and evolution to the molecular-scale development of new technologies. These goals are achieved through the development of designer fusion proteins that combine domains and functions from unrelated proteins and enzymes. We typically combine rational protein engineering with genetic selection to create and fine-tune the desired activities. In oseparations, we have combined a previously developed pH-sensitive self-cleaving protein with a variety of purification tags to produce simple and economical methods for purifying recombinant proteins. Our most recent work involves rational and evolutionary approaches to optimizing our self-cleaving tags for use in a wider variety of expression hosts. In biosensing, we have developed allosteric proteins that incorporate human hormone receptors, and have used these proteins to generate Escherichia coli strains that are growth-dependent on hormones and hormone-like compounds. Remarkably, this genetically simple bacterial sensor can differentiate agonist from antagonist activities and has been effective in detecting a wide variety of strong and weak estrogenic compounds. More recently, we have applied this system to the discovery of thyroid active compounds, as well as the evaluation of environmental endocrine disruptors in humans and animals, and even the discovery of possible autism-associated environmental factors. Applications of our designed proteins are far-reaching, and include drug discovery, biosensing, drug activation, reversible knockouts for metabolic research, new genetic selection systems, and advanced cellular control strategies.