The sequence of the human genome will help identify genetic mutations that cause disease, and a central goal in the post-genomic era will be to develop tools to correct these errors. The repair of complex genomes requires having reagents available that 1) are capable of locating a specific sequence from among several hundred megabases of non-specific DNA and 2) are able to catalyze specific molecular modifications of the DNA that either initiate an endogenous repair pathway or effect repair directly.
Our laboratory has focused on designing and engineering homing endonucleases with novel functions that have the potential to facilitate DNA repair and other molecular processes. Homing endonucleases are encoded by mobile DNA elements that propagate between individuals within a population by “homing,” and between species through lateral transmission. These enzymes initiate homing by introducing a double-strand break at a single genomic target sequence situated within a cognate allele that lacks the mobile element. A long term goal of our group is to harness the extreme DNA sequence specificity of homing endonucleases to catalyze specified events at targeted genomic loci.
Our laboratory applies directed evolution and rational design strategies that are based on structural and phylogenetic information in order to design homing endonucleases with novel functions.