Structure, Mechanism and Evolution of the Nuclear Pore Complex
		Our lab focuses on aspects of the nuclear information pathway; how macromolecular complexes dynamically interact control the passage and transport of genetic information from intranuclear DNA via RNA through the nuclear pore complexes (NPCs). As the sole mediator of nucleocytoplasmic exchange across the nuclear envelope that encloses eukaryotic DNA, NPCs thus define the contents of the nucleus. The pivotal role of the NPC in controlling communication between the genetic material and the rest of the cell is reflected in the many oncogenic and developmental defects directly associated with alterations in nucleocytoplasmic transport. Nucleocytoplasmic transport depends on the interplay between transport cargoes (which carry NLS or NES targeting sequences), their cognate soluble transport factors (many termed kaps), and NPCs. Read more...

Kinetic Studies of Nuclear Import Pathways In Vivo
		We are studying the kinetics and interactions between transport factors, transport cargoes, and NPC. Multiple karyopherins carry cargoes across the NPC; we have therefore developed an improved in vivo nuclear import assay to further characterize the reason why alternative pathways across the NPC should exist. We had previously described Kap123p as an alternative karyopherin that is involved in the nuclear import of ribosomal proteins. Read more...

The Nuclear Periphery and the Oncogenic Protein Mlp/Tpr: Functional Studies of its Yeast Homolog
		The instructions encoded in the DNA present in each cell are at the heart of regulating cell growth and development in organisms as diverse as yeast and humans. Exciting recent discoveries point to how it is not just changes in the instructions themselves, but how they are organized and controlled, that cause cancers. Read more...

Virtual Gating Machines for Protein Purification
		Most commercial large-scale production of proteins uses column chromatography and synthetic membranes to fractionate and concentrate proteins. Though the requisite multiple recovery steps increase purity, yields drop quickly and expenses rise. Improving the performance of these processes is therefore a high priority. Nature has already solved this kind of protein enrichment problem with the nuclear pore complex (NPC), the macromolecular machine that efficiently segregates proteins between the nucleus and cytoplasm of all eukaryotic cells. Read more...

New Tools for Exploring the Dynamic Interactome
		In this project, we seek to revolutionize proteomics by synergistically combining improvements in established techniques with new approaches. To accomplish this, we are collaborating with several laboratories to develop the methodologies required to study other aspects of the nuclear information pathway within yeast and other organisms. First, we are devising methods to determine the normal flux of structural proteins & regulatory factors that together comprise dynamic segments of the genome. Second, we are following the course of RNA after transcription, as it is processed, packaged & exported from the nucleus; in particular, we are focusing on the accessory proteins that process rRNA during its maturation into ribosomal subunits. Finally, we will expose how two pathogenic human viruses, HIV & CMV, subvert their host's genetic information pathway & supplant it with their own, causing cell death and even defects in cell cycle control that lead to oncogenesis. Read more...