Dr. Rice’s research is centered on investigating protein-DNA recognition, particularly the role of DNA structure and flexibility in the process and on understanding mechanisms of genetic recombination at a structural level.

DNA recognition studies use as examples two members of a ubiquitous prokaryotic family of histone-like proteins, IHF and HU. IHF recognizes a specific DNA sequence, but does so entirely through indirect readout of the sequence-dependent conformation parameters of the DNA rather than through direct side chain – to – base contacts. The Rice group is focusing on mutants of IHF that display relaxed sequence specificity. They have determined a series of crystal structures of all combinations of mutant and WT IHF bound to mutant and WT DNA sites. Combined with their in vitro measurements of Kd for these complexes, these studies highlight the crucial rule played by sequence-dependent DNA twist in DNA sequence recognition. HU is closely related to IHF. It binds DNA without significant specificity but strongly prefers distorted DNA sites. The Rice group has recently determined a high-resolution structure of Anabaena HU bound to a DNA duplex with several unpaired and mis-paired bases. This structure addresses a number of questions regarding the size of the bend induced by HU binding, the size of its binding site, and how it accommodates unusual DNA structures.

Flp recombinase is being studied as a model system for understanding basic science questions such the strategies used by proteins to recognize, distort, and manipulate DNA and mechanisms for coordination of catalysis in multisubunit protein-DNA complexes. It was also chosen for study due to its practical use as a tool for genetic manipulations. The Rice group as determined two crystal structures of Flp bound to trapped Holliday junctions that mimic an intermediate of the recombination reaction. They have also undertaken a series of site-directed mutagenesis and kinetic experiments to further understand the catalytic mechanism of the enzyme. A greater understanding of genetic recombination in mammals will be critical for developing new mouse models for diabetes research.