Project Summary/Abstract Aided by technological advances in molecular biology, synchrotron X-rays, crystal cooling, detectors and phasing methods there has been an explosive growth in synchrotron-based macromolecular structure determination. Many facilities have upgraded their beamlines to meet this demand as well as offer new capabilities, such as data collection from micro crystals (crystals with one dimension less than 20 microns). This proposal is a direct reflection of the desire of the Southeast Regional Collaborative Access Team's (SER-CAT) membership -- 130 plus research groups from 27 institutions (academic, industry, private and government) -- to extend microdiffraction capabilities on beamline 22ID by the purchase of the ARINAX MD3Up micro-diffractometer to accommodate 1-micron (today) or smaller (tomorrow - post APS upgrade) X- ray beams. This desire is based on three factors. First our current MD2 micro diffractometer is obsolete. It will be 10 years old before a new instrument can replace it and key components (circuit boards, optical components, etc.) are no longer available. A catastrophic failure of the MD2 would shut down 22ID for 4-6 months, significantly disrupting the research of 100 NIH funded projects. Since over 98% of data collected at SER-CAT is done so remotely, many Member institutions no longer have an in-house diffraction facility. For these Institutions the impact of such a failure would be even greater. Thus, good management requires that SER-CAT immediately begin exploring replacement options for the MD2. Second, limitations in the MD2's precision, sphere of confusion, optics and maximum rotation speed does not allow SER-CAT to fully utilize the 1-micron beams being produced by recent installation of optics (KB mirrors) and detector upgrade (100 Hz Eiger 16M detector) on 22ID. In short, the MD2 lacks the precision and sphere of confusion of the MD3Up (0.1 micron), is needed to maintain a 1-micron crystal in a 1-micron X-ray beam while rotating at 100°/sec. Finally, new features of the proposed MD3Up micro-diffractometer such automated plate scanning and kappa axis calibration will allow us to expand the 22ID experimental envelope to include room temperature serial crystallography (plate scanner attachment or chip scanning) and precise alignment of the crystal in the X-ray beam and goniometer (mini-kappa attachment), which will improve data quality and signal to noise. SER-CAT believes that the MD3Up represents the most cost-effective solution for providing high precision microdiffraction capabilities for today and tomorrow, increasing research productivity and improving the cost- effectiveness of beamline operation for both micro and general diffraction experiments. This in turn will result in more and better science being produced.

PROJECT NARRATIVE  The requested instrument will support research related to over 100 NIH extramural funded projects that are  of  fundamental  importance  and  directly  relevant  to  human  health,  including  cancer,  diabetes,  sepsis,  anemias,  ataxias,  bacterial  and  viral  infections  and  many  others.  The  proposed  equipment  will  directly  impact  the  rate  at  which  we  can  solve  important  structures,  increase  the  number  projects  we  can  tackle  and allow us to better meet the challenges of the future. The expectation is that the knowledge gained from  these high-­resolution crystal structures will eventually lead to better treatments for human disease.