This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The Hol laboratory is focused on proteins from major global pathogens that are promising targets for the development of much-needed new pharmaceuticals to treat such diseases as malaria, sleeping sickness, leishmaniasis, tuberculosis and cholera. A characteristic of the laboratory is to study proteins and in particular multi-proteins assemblies that are, by themselves, extremely interesting with respect to architecture, function and properties and then aim for novel ways to obtain high affinity inhibitors. As a result we are investigating mainly multi-protein assemblies, including cholera toxin in complex with human proteins, the unique U-insertion/deletion RNA editing system in Trypanosomatids, Peroxins involved in glycosome biogenesis, the invasion machinery of the malaria parasite, and the Type 2 Secretion System which exports cholera toxin across the outer membrane of Vibrio cholerae.