We request funds to purchase 180 high-memory parallel computer nodes to support data and computationally intensive, NIH-funded, biomedical research at Vanderbilt University and Medical Center. The proposed system will facilitate many applications that require high memory/processor supercomputer performance at a small fraction of the cost. This system will be built aside our successful 4000-processor parallel computer known as the Advanced Computing Center for Research and Education (ACCRE) at Vanderbilt, which supports high-performance computing for research from elementary particle investigations using the Large Hadron Collider to model system genetics to human behavioral studies. Despite our successes with the existing cluster, many state-of-the-art biomedical computation projects have become memory hogs, and thus caused severe inefficiencies in our current system. These projects include macromolecular structure prediction, next-generation sequencing, multi-dimensional imaging, and proteomic identification. ACCRE users have access to the instrument and training through our established infrastructure. ACCRE is a grass-roots organization that was initially created by faculty from throughout the institution and later awarded the strong institutional support it enjoys today. It was initially established through a Major Research instrumentation Grant from NIH in 2004 along with Departments of Defense and Energy grants to the School of Engineering and Department of Physics. ACCRE was upgraded through another NIH Shared Instrumentation Grant awarded in 2009. ACCRE is managed by three co-directors, one each from the College of Arts and Science, School of Engineering, and School of Medicine (of which Dr. Piston is the co- director). In keeping with the tradition of bottom-up ownership of ACCRE, policy and procedures are set by the co-directors upon recommendations of the Faculty Advisory Board, which consists of 10 active PI users. The proposed parallel computer will be used directly by more than 20 NIH-funded researcher groups and its impact will reach many more investigators through outreach efforts of centralized facilities such as the Center for Structural Biology, the Center for Human Genetics Research, The Small Animal and Cell Imaging Resources, and the Proteomics Core Laboratory. In this manner, the equipment will support more than 100 NIH grants. The major users of the system have primary appointments in six different departments within the Vanderbilt University School of Medicine, College of Arts and Science, and School of Engineering. Research programs with unmet demand for high memory node computation are concentrated in structural biology, human genetics, imaging, and proteomics. These new high memory nodes will make it possible to carry out data and computationally intensive biomedical investigations otherwise not feasible thus significantly increasing the rate of scientific discovery in a variety of biomedical disciplins.