Macromolecular Diffraction at the Cornell High Energy Synchrotron Source (MacCHESS) is a facility dedicated to helping to answer questions of biomedical and basic biological relevance, through the development of new technology and methods that benefit both scientific collaborators and the broader structural biology community. Research areas being investigated by MacCHESS scientists, collaborators, and users include probing the mechanisms by which DNA expression, RNA-splicing and translation are regulated, understanding how proteins are trafficked and bind to specific membranes within cells, and identifying the structural features of complex signaling assemblies that underlie the control of cell growth, differentiation, and development. When these processes are not properly regulated, a variety of pathological conditions and disease states can result, including cancer and neurodegenerative disorders. An over-riding goal of the technology development and research at MacCHESS is to obtain information that can be applied to the identification of new therapeutic targets and clinical strategies. Notwithstanding the current excitement surrounding cryo-electron microscopy, the techniques of X-ray crystallography and small-angle and wide-angle X-ray scattering (SAXS/WAXS) in solution are essential methods for obtaining structural information. They can be used at room temperature, and SAXS experiments, in solution, can be performed relatively close to physiological conditions. Additionally, time-resolved experiments can follow the course of reactions, providing information relevant to the dynamic environment in a cell. MacCHESS has demonstrated its importance as a resource at which excellent crystallographic and SAXS data may be obtained. Moreover, it has served as a testbed for development of techniques to make acquisition of these data faster, easier, and more accurate. A transition from a P41 to a P30 grant mechanism is pending; this will change the emphasis of MacCHESS but not its importance as a resource for both scientists collecting routine data and those seeking to develop new techniques. The success of the resource is largely due to the excellence of its staff, and retention of this staff during the gap between the end of our current grant and the beginning of a new grant is essential to offering users the exceptional support expected at CHESS. During the CHESS-U down in 2018, MacCHESS staff will have an opportunity to assist in upgrading CHESS as well as to improve the MacCHESS resource to provide future users with a top-of-the-line research experience. We seek funding to maintain our excellent resource during the next year.
Structural information is essential for understanding the molecular basis of a number of disease states. Two of the most important methods for obtaining such information are X-ray crystallography and SAXS/WAXS. MacCHESS provides not only a facility at which biologists can obtain information critical to determining structure-function relationships, but also a resource for the development of next-generation techniques to acquire new information which will lead to a deeper understanding of biological processes.
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