Macromolecular Crystallography Shared Resource: Project Summary Chemistry Shared Resource Group The ability to determine the structure of proteins using X-ray crystallography has been one of the great scientific achievements over the past 50 to 60 years. It has provided broad insights into many areas of biology, ranging from the evolution of life, to understanding the chemistry of enzyme catalysis, to the control of cell growth and death. More recent applications have included producing the binding maps against which targeted drugs can be designed and evaluated leading to unparalleled growth in effective, safe therapeutics. As such, X-ray crystallography is an essential tool for the Purdue University Center for Cancer Research (PCCR) to carry out its mission - to uncover the fundamental sources of cell growth anomalies associated with cancer and to develop new and effective therapeutics through structure-based drug design. Accordingly, the primary mission of the Macromolecular Crystallography Shared Resource (MM-SR) is to provide access to state-of-the-art technologies, hardware and expertise to PCCR members who use X-ray crystallography to address cancer-related questions and develop anti-cancer therapeutics. Formally established as a Shared Resource in 1998, this Resource has been committed to the support of macromolecular crystallography projects of PCCR researchers. The MM-SR has been a crucial resource to PCCR members studying cancer mechanisms and mutations, visualizing cancer-related drug targets and performing iterative, structure-based design of anti-cancer therapeutics. To enable the research of X-ray crystallography expert and non-expert PCCR members, the MM-SR provides and maintains in-house equipment and computational resources for data collection and processing, robotic systems for high- throughput micro crystallization experiments and for their imaging and storage, and temperature-controlled rooms. The MM-SR's services and support are critical to the PCCR members' research needs because X-ray crystallography requires that sophisticated and dedicated resources be immediately and locally available to researchers. Because of the high associated costs and need for technical support, the X-ray data collection and crystallization hardware resources provided by the MM-SR are beyond the budgets and group size of most individual labs. This is especially true of the robotic crystallization and robotic visualization systems, which are key technologies that substantially accelerate the empirical process of identifying crystallization conditions and also allow, through microliter to nanoliter experiments, the preservation of precious biological material. By providing centralized hardware and expertise in a shared resource, MM-SR makes these essential technologies widely available to PCCR members, promoting productivity and scientific interaction.