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Area of Expertise: Protein-DNA interactions and protein
engineering of homing endonucleases
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.