"Gene regulation is fundamental to the proper functioning of a cell, and many cancers can be traced to abnormal gene regulation. Our goal is to understand how genes are regulated by combining genetic, biochemical and structural descriptions. Our expectation is that such information will contribute to the development of future therapeutic agents against cancer and other human diseases.
We are particularly interested in how chromatin enzymes recognize and interact with the nucleosome. Despite the hundreds of chromatin enzymes discovered and characterized in vivo, we currently lack a molecular understanding of how these proteins bind to their physiological substrate, the nucleosome. To this end, we perform biochemical studies of chromatin enzymes and nucleosomes, and we use X-ray crystallography to determine their three-dimensional structures.
The two rate-limiting steps in structure determination of large complexes by X-ray crystallography are generating large quantities of high purity material and crystallizing the complexes. We have developed methods for reconstituting recombinant multicomponent complexes and we continue research to improve those methods. We are also investigating novel methods and tools for crystallizing multicomponent complexes.
For more information including pictures and movies of proteins and DNA, please visit our lab's web site.
Crystal structure of the RCC1/nucleosome complex.
Production of recombinant protein complexes for crystallization by polycistronic expression