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My laboratory studies the structure and assembly of small DNA viruses. Specifically we are addressing three fundamental control points : 1) how is capsid assembly prevented in the cytoplasm, 2) how do the capsid proteins identify their genome for encapsidation, and 3) are specific nuclear sites used as 'workbenches' to couple viral DNA replication with capsid assembly. Our study of human papillomavirus assembly has been translated into the development of vaccine reagents for the prevention of cervical cancer. We have found that subunits of the virus capsid (capsomeres) are as effective in eliciting a protective immune response as recombinant virus-like particles, and can be economically manufactured using bacterial expression. We are now developing a capsomeric vaccine as a next generation prophylactic vaccine for use in resource-poor areas of the world. In addition, we are applying new technologies to a variety of vaccines in order to generate thermostable, single-shot formulations.