A state-of-the-art center within the Department of Structural Biology for biomolecular X-ray crystallography across St. Jude Children’s Research Hospital.
The Biomolecular X-Ray Crystallography Center in the Department of Structural Biology is a shared resource designed to facilitate studies of protein and macromolecular structure and function by investigators at St. Jude Children’s Research Hospital.
The Center has determined thousands of structures from a myriad of biological systems. Those atomic-resolution structures, ranging from small molecules and peptides to macromolecular assemblies of proteins and nucleic acids, serve as foundation for drug discovery efforts at St. Jude and offer exquisite insight into molecular recognition in various biological processes.
The Center is staffed by expert scientists with extensive experience in all aspects of crystallography for high-quality structure determination. The staff is committed to training and supporting researchers at every level who wish to apply X-ray crystallography to their projects. Collaborations are welcomed.
Access: Researchers from inside or outside the Department of Structural Biology can engage with the Center in multiple ways — full-service partnerships; mentor-mentee collaborations where training is desired, with hands-on training sessions covering all aspects of the crystallography process; and independent use of instruments for experts and previously trained users. Please contact the director with requests for consultation and assistance with project planning, experimental design, crystallization, data collection, structure determination, structure interpretation and manuscript preparation.
The Center is equipped with numerous instruments that enable every aspect of macromolecular crystallography.
Crystallization, imaging and storage. Two crystallization robots allow rapid nanoliter dispensing for efficient screening of a large number of conditions to identify crystal hits. The Mosquito LCP (SPT Labtech) with humidification chamber is the most versatile and allows crystallization of membrane proteins using lipidic mesophases. The Center houses 20 °C and 4 °C Rock Imager 1000 plate hotels (Formulatrix) automated for high-quality image capture using visible, cross-polarized and UV light. For efficient crystal optimization, the Dragonfly liquid handler (SPT Labtech) aids in custom 96-well screen formulation. Dedicated 20 °C and 4 °C walk-in rooms with stereomicroscopes are available for plate storage, visualization, and crystal manipulation.
Data collection and computing. St. Jude researchers working with the Center routinely collect synchrotron data remotely using a dedicated workstation within the Center. As a member of the SouthEast Regional Collaborative Access Team (SER-CAT), St. Jude researchers enjoy regular access to the Advanced Photon Source (18 days annually). The Center also has access to cutting-edge National Synchtrotron Light Source II (NSLS-II) beamlines: Frontier Microfocusing Macromolecular Crystallography (FMX) for challenging protein crystals requiring the latest micro-focusing technology and Highly Automated Macromolecular Crystallography (AMX) for high-throughput drug-discovery. In addition, the Center maintains an in-house X-ray diffraction laboratory equipped with a Bruker AXS D8 Venture system for diffraction screening and data collection on larger well-diffracting crystals. The Center features full-service raw data management and extensive Linux computing infrastructure for efficient data processing, structure determination and post-structure analysis.
Darcie Miller received her PhD in Biochemistry from UT Austin, focusing on structure-based drug discovery through protein X-ray crystallography, biochemistry, and molecular modeling. As an NIH postdoctoral trainee at the Northwestern University Feinberg School of Medicine, she was part of the NIH Protein Structure Initiative (PSI), solving de novo structures and characterizing proteins through structural and bioinformatics approaches. She joined St. Jude in 2004 to pursue science in a collaborative, therapeutics-focused setting and became staff member in 2007, performing independent research in collaboration with faculty across the institution and training junior scientists in all aspects of macromolecular X-ray crystallography. With 15 years of experience in facility management and operations. Dr. Miller has expanded facility usage and resource acquisition through internal funding and external partnerships. Since becoming Director in 2017, she has served as the voting board member and state representative for St. Jude’s membership in SER-CAT at APS. She is Principal Investigator on proposals securing access to state-of-the-art beamlines at NSLS-II, BNL, and serves as an NSLS-II Structural Biology peer reviewer. Dr. Miller is passionate about mentorship and training of junior scientists to meet tomorrow’s challenges.