One day in March of 2006, postdoc Mike Lawrence walked into David Liu's laboratory at Harvard University in a slightly anxious mood. He'd been in the lab for nine months with little to show in terms of good results, and he was hoping this day might turn things around. He had taken on a bold new project with his labmate, Kevin Phillips, to test whether changing the charge of surface residues on a protein could reduce its propensity for aggregating.
Preventing aggregation could be appealing for a number of reasons: understanding neurodegenerative diseases, extending the shelf life of protein therapeutics, and producing better-behaving proteins for lab work such as crystallography. In all of these examples, a protein's propensity for aggregating can wreak havoc on attempts to control its behavior.
Instead of taking the route most scientists might take to avoid aggregation – systematically changing just one amino acid at a ...