As biological phenomena are fundamentally defined at the molecular level, it is critically important to understand the structures and dynamics of biomolecules and their complexes. The growing power of structural biology is therefore playing an increasingly important role in cancer biology; both in defining the structures and functions of cancer-related protein and nucleic acid complexes, and in providing a starting point for the "rational" design of new therapeutics.

The University of Utah Medical Center has active research groups studying cancer biology using each of the three high-resolution methods of modern structural biology: X-ray crystallography, NMR, and cryo-electron microscopy. State of the art instrumentation is housed in Centers for Biomolecular NMR spectroscopy (Varian 500 and 600 MHz NMR spectrometers), X-ray crystallography (RU200 rotating anode X-ray sources with R-Axis image plate detectors), and Electron Microscopy (Philips Tecnai 12 and Hitachi 7100 cryo-TEM diffraction systems). These facilities are maintained by specialized research groups, and collaborative studies with the larger cancer biology community strongly encouraged. Excellent facilities are also available for complementary biophysical studies, including mass spectrometry, optical, fluorescence, CD, and surface plasmon resonance spectroscopies, microcalorimetry, and analytical ultracentrifugation.

Participating Faculty

Sherwood Casjens - We are interested in the mechanisms by which large multi-subunit protein and nucleic acid macromolecular structures assemble. We are currently studying catalysis of macromolecular assembly by proteins that do not become part of the structure in the bacteriophage P22 model system. We use a combination of genetics, genomics, biochemistry and protein structure determination to study bacteriophage P22 assembly.

Christopher P. Hill - We are interested in how protein molecules associate to form complexes and machines that function in processes such as the assembly and maturation of HIV particles and the regulation of intracellular proteolysis. These studies are aimed at understanding the regulation of fundamental cellular events such as cell-cycle progression. Our primary approach is to determine the three-dimensional structure of individual proteins and complexes by the techniques of x-ray crystallography.

Wes Sundquist - Our laboratory is interested in understanding the process of HIV assembly and its role in facilitating viral replication. HIV assembly is a challenging problem because it occurs in multiple stages, involves both cellular and viral factors, and produces particles that are highly organized, but not strictly regular. We have therefore adopted a multidisciplinary approach to studying the problem of viral assembly, using both classical structural methods (NMR, X-ray crystallography, and electron microscopy), as well as biochemical and genetic approaches.