Using mouse models as well as zebrafish, Engle and her colleagues conducted functional studies of mutated genes and their normal and abnormal proteins. “We identify the mutation in humans,” she said, “and if we put it into the mouse we can recapitulate the human phenotype and then study why it happened.” What Engle has learned is that the trouble with eye movement is often caused not by a loss of gene function, but by altered or, on occasion, increased function. In Duane syndrome, for instance, they found that the overactivity of one protein, α2-chimaerin, impairs the ability of one small set of embryonic neurons to respond to growth signals. As a result, axon growth “stalls out” and never makes it to the target muscle.
Chapter Two in the lab overlapped with a new chapter in Engle’s personal life as well – her marriage in 2001 to Paul Dennehy, a photographer from Cork City, Ireland, whom she met through a mutual friend while on vacation in Nantucket. Two years later came the arrival of their daughter, Saoirse, whose name is Gaelic for “freedom.” They adopted her from China when she was 10 months old.