Antibody and Enzyme Engineering with an emphasis on developing better methods for recombinant antibody or enzyme cloning and directed evolution. In collaboration with the Georgiou group (UT Chemical Engineering) several new technologies have been developed based on E. coli expression / FACS selection which have allowed us to enhance antibody affinity to remarkable levels, as well as quantitatively analyze the protein evolution process with an unprecedented level of precision. Several important antibodies have been developed including one currently being evaluated as a therapeutic prophylactic/intervention for anthrax infection. We have recently extended the work to include manipulation of enzyme catalysts.




Artificial macromolecules with defined higher order structure and function These systems involve the predictable folding of synthetic molecules into stable scaffolds, based on abiotic secondary structure elements. Our first generation molecules, called aedamers , fold in aqueous solution due to the stacking of alternating electron rich and electron deficient aromatic units. We have expanded this work to include a novel intermolecular recognition motif in water as well as applications to liquid crystals.

The chemistry of nucleic acid binding, recognition and modification with a primary focus on understanding and exploiting our newly created polyintercalating molecules. These molecules show sequence specificity, are amenable to combinatorial techniques and some derivatives are active against gram positive bacteria. We have recently used high filed NMR to determine the structure of the first threading tetraintercalator bound to its preferred site in double stranded DNA.