Genomic and EST sequencing projects are providing a sequence infrastructure that is changing how protein biochemistry is practiced. These data along with mass spectrometry provide the cornerstone technologies fueling the proteomics revolution. Our group is focused on developing tools and strategies in proteomics to answer basic biological questions. By coupling the additional amino acid sequence information that can be obtained using peptide tandem mass spectrometry to "back-end" database searching and "front-end" separative techniques, we are able to directly analyze extremely complex protein mixtures. The applications for these technologies vary from analyzing purified protein complexes to studying host-pathogen interactions in diseases such as malaria or anthrax. We are further extending these applications to find post-translational modifications to the proteins within these same complex mixtures.