Our laboratory is investigating the molecular mechanism of what has been called the “keystone complex” of DNA repair, the Mre11/Rad50 (MR) complex. The MR complex is highly conserved throughout all kingdoms of life and is involved in the repair of the most drastic form of DNA damage, the double strand break.   We are examining the structure/function relationships and allosteric regulatory mechanisms of the MR complex using the techniques of enzymology and molecular biophysics.   Our overall goal is to understand how the MR complex carries out its activities on a molecular level.

We are investigating the enzymes responsible for replicating the apicoplast genome in Plasmodia falciparum, the most prevalent causative agent of Malaria.  The apicoplast is a unique organelle found in animal parasites of the phyla Apicomplexa.  The apicoplast is a evolutionarily related to the chloroplast of red algae and contains a 35 kb genome.  The genome is replicating using a minimal set of proteins:  a DNA polymerase, primase, helicase, and single-stranded binding proteins.  We our examining each of these proteins individually and as a single unit termed the replisome.  We are employing a variety of biochemical and biophysical techniques to elucidate the detailed mechanism by which apicoplast DNA is replicated.  We are also developing high-throughput assays for each of the apicoplast DNA replication enzymes to facilitate the screening of small-molecule inhibitors that may act as lead compounds in anti-malarial drug discovery efforts.