Michael J. Harms, Ph.D.

Research

The goal of my research is to trace the evolution of a multifaceted protein by resurrecting and studying its molecular ancestors. The protein, named calprotectin, plays multiple roles in the human immune response: In addition to promoting inflammation, it thwarts infections by sopping up the metals microbes need to thrive. To determine how this one protein evolved to perform such different roles, I will use an approach based in biochemistry, biophysics, and molecular evolution to reconstruct the evolutionary precursors of the modern-day form of the calprotectin. I will synthesize these extinct proteins in the laboratory and examine their properties to determine when, during the course of its evolution, calprotectin acquired its diverse capabilities. In preliminary results, I have produced the most ancient, ancestral forms of calprotectin and have found that they don't display the antimicrobial activities of the present-day protein--a capability that must have evolved more recently. This work will help illuminate how immunity has evolved, and it could provide new strategies to design anti-inflammatory drugs.