What are the underlying principles of maturation of the immune response?

Native or germ cells express antibody proteins of very low selectivity and low affinity. After exposure to a pathogen, the organism begins to express antibodies of higher affinity that are more selective.  This project seeks to understand the molecular principles behind this so called affinity maturation process.  Can it be that the process involves rigidification of the binding site and what are the molecular determinants of this loss of flexibility?  In order to answer these questions, we measure the distribution of lifetimes of the tryptophan residues that line the active pocket of the binding site of the antibody using phase shift fluorescence spectroscopy.

This work grew out of a five year project funded by NSF and in collaboration with Professors Richard Goldsby, David Ratner, and David Hansen. See representative publications below.  Over 25 undergraduates have worked on this project in the O'Hara lab in the last 15 years.  The work of two of our most recent graduates, Cristina Irimia '08,  and Chantae Sullivan '07 is described in the postings below.  Dr. Richmond Ampiah-Bonney continues work in this area today.