Donald Doyle

Nuclear hormone receptors control the expression of genes in response to small molecule hormones. In performing this activity, the receptors must specifically recognize small molecules, DNA, and other proteins. The amino acids that recognize each of these substrates are varied using genetic engineering techniques until a receptor with novel recognition is created. The original and new receptors are studied using a variety of biophysical techniques to elucidate the principles behind the new activity. This exercise provides both new knowledge for future protein engineering and real materials for research and medical applications. 

We engineer new receptors to turn on gene expression in response to specifically chosen small molecules. The small molecule may be chosen for its properties in the specific application. For applications in gene therapy and use as a tailored gene switch, the small molecule may be chosen due toits long or short pharmacokinetic half-life, because it crosses the blood-brain barrier, or other tissue specificity. For applications in synthetic biology gene circuits, the small molecule may be chosen for its interactions with other circuits in a network. Another application is in assembling the biosynthetic components (enzymes) to synthesize the small molecule via genetic selection.