Claire Elizabeth Dunne Fraser

A.B., Princeton University
KH Domains on Brain Polyribosomes: FMRP and Nova in Translational Regulation
presented by Robert B. Darnell (on behalf of himself and Jennifer Darnell)

Claire Dunne Fraser came to our laboratory from Princeton University with an outstanding record of 3.7 grade point average and one of the most powerful personal statements I’ve ever seen about why she wanted to be an M.D.-Ph.D. student. She noted after working as a volunteer in Haiti in a city ghetto that it’s built on a garbage dump and yet there’s a wonderful spark of life there, which is terribly perplexing. This ability to see a problem from two opposite sides at the same time is special, and it came with Claire directly into the lab where she began to focus on a different kind of suffering that’s seen in a syndrome called the fragile X syndrome. This is the commonest form of inherited mental retardation and despite cloning of the gene in 1990, its function is very poorly understood. But for Claire its study offered a perfect template for bringing together two seemingly opposite worlds of neuroscience: the approach of studying molecules with the big picture approach of how we think.

Her scientific breakthrough came after several years of hard work on this problem when she realized a way to tie the two together in a brilliant single experiment. I hope the excitement of that experiment will live on with Claire as it will in our laboratory and in the literature. Claire was able to show that the mutation causing the fragile X syndrome was linked to the detailed molecular biology of the protein, and together with Jennifer Darnell, my wife and colleague in the lab, found that this mutation also regulates specific RNAs in the brain. Thus the loss of the single protein, this fragile X mental retardation protein, disrupts RNA regulation, which is a mysterious way of regulating gene expression, in a manner sufficient to disrupt the way we normally think. Those of us who have worked with her know that Claire will be successful in using her own mind to continue building such bridges between what may seem to be opposing areas of scientific thinking as she moves forward in her dual career as a physician-scientist.