MRI: Acquisition of X-Ray protein crystallography equipment at Northeastern University

Northeastern University, Boston MA

Investigators

Abstract

This grant is for the purchase of X-ray macromolecular crystallography equipment at Northeastern University. X-ray crystallography provides one of the most powerful venues for the visualization of proteins and other macromolecules in three dimensions at near atomic resolution. It is at the heart of structural biology, giving access to experimental data that allows scientists to make the connection between what molecules "look like" and how they function. The HighFlux HomeLab, consisting of the Rigaku MicroMax-007HF X-ray generator, with state-of-the-art optics, X-ray detector and cryo-system, enables high-quality crystallographic data collection with secure and automated features that facilitate access to research groups with diverse scientific interests and expertise. Until recently the kind of data that reveals molecular details of biological molecules at atomic resolution, particularly for small and fragile crystals, required travel to national laboratories such as the Advanced Photon Source at Argonne National Laboratory and other synchrotron X-ray sources. Synchrotron facilities are available to a specialized group of scientists with extensive experience in crystallography. The HighFlux HomeLab at Northeastern University will provide the venue for expert X-ray crystallographers to perform cutting edge research with close involvement of graduate and undergraduate students as well as for non-experts to expand the scope of their research to include structural biology. This equipment is highly complementary to structural biology equipment already present at Northeastern in the areas of Nuclear Magnetic Resonance spectroscopy, Mass Spectrometry, Electron Paramagnetic Resonance spectroscopy and computational equipment, thus completing the major set of biophysical approaches used in state of the art structural biology research. Scientific questions being addressed through this project will help elucidate fundamental understanding of cell signaling, DNA damage and repair, enzyme catalysis as well as more practical applications of structural biology to energy production, human disease and biomolecular engineering, the success of which is built on understanding fundamental processes. Central to the use of the X-ray equipment will be a course in Macromolecular Crystallography, staged in the form of a workshop designed to integrate research, teaching and training in structural biology. Northeastern is at the forefront of experiential learning, with a Co-op system that places undergraduates in laboratories across campus, in the Boston area and beyond, for extended periods of full time research. The workshop will have input and support from the PI and coPIs, a facility's manager with a Ph.D. and extensive experience in macromolecular crystallography, an academic specialist and a graduate teaching assistant. This workshop course will welcome faculty, graduate and undergraduate students interested in X-ray data collection, structure refinement and analysis. Students will be encouraged to bring their own crystals, but projects will also be available associated with the PI's and coPI's research groups. As research in the 21st century becomes ever more multidisciplinary, this course will provide "hands on" experience so that researchers in various areas of expertise can integrate structural biology in thinking about their science, with the ability to make a critical assessment not only of structures collected at Northeastern, but also of those deposited in the Protein Data Bank, along with the associated data. The highly integrated research, teaching and learning environment enabled by this project will take place in a very diverse environment in terms of the researchers involved. In addition to being highly productive scholars the senior personnel on this project are diverse in terms of race, ethnicity and gender. Four out of the five are women, one Latina, one Native American and one African American. Current graduate and undergraduate students in the PI's and coPI's laboratories include 26 women, 18 men, 5 African Americans, 2 Native Americans and 1 Latina. Young women and minorities on this project will see the possibilities of success for themselves as reflected in their role models and will be encouraged to continue to do science, helping to increase representation for these groups in our scientific research communities nation wide.