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.
This project consisted of setting up a protein X-ray crystallography facility at Northeastern University. The centerpiece of this facility, purchased with NSF support, consists of the HighFlux HomeLab equipment which will allow Northeastern University faculty, students and other researchers to collect X-ray data to solve the 3-dimensional structures of proteins and other macromolecules at atomic or near-atomic resolution. This is an essential part of understanding how proteins work and therefore how they contribute to life in the cell and within organisms. Intellectual merit During this year of funding the HighFlux HomeLab X-ray equpiment was purchased and installed into a newly renovated room. Northeastern University has committed funds to support a full time facility's manager who will maintain the equipment, train faculty and students to use it, and run a workshop with Professor Carla Mattos (PI on the grant) where students will gain knowledge of the theory and practical aspects of protein X-ray crystallography while advancing their own research. The PI is currently interviewing candidates for this position. The workshop will start running in the Spring 2014. Since the equipment finished being installed in July 2013, several data sets have been collected on wild type and mutants of Ras GTPase, a key protein involved in transducing signals from outside of the cell to the nucleus through protein-protein interactions that result in the control of cell proliferation. Several students are now in the process of solving the structures of these proteins. Broader Impact In the short time that the new X-ray equipment has been functional at Northeastern Uniersity two graduate students and four undergraduate students have been trained and collected data for solving the structures of proteins. Two of the undergraduates were supported by Research Experience for Undergraduates funds by the NSF to do full-time research during the summer. Both are African Americans, one at Northeastern University and the other at Langston University in Oklahoma. The Northeastern student has recently been selected to present his structures at a nationwide conference organized by the Council for Undergraduate Research. Through this opportunity, this young African American scientist will have a chance to present his work and get recognized for it. This will be the first presentation of structures solved from data collected using the new HighFlux HomeLab. The training of a diverse group of students is expected to intensify as the workshop becomes a regular venue for learning crystallography at Northeastern, while providing the opportunity for students to gaining hands-on experinece on equipment and critical thinking skills related to a research project.
