Nanoliter crystallization facility
Three-dimensional structural information is crucial for understanding how macromolecules (e.g., proteins) function and designing small molecule inhibitors to modulate their activities in drug discovery. X-ray crystallography is one of the most powerful and popular techniques used in elucidating the atomic level details of macromolecules and their complexes. However, obtaining high-quality (“diffraction-quality”) crystalline samples represents a significant (usually the biggest) bottleneck in the workflow of macromolecular structure determination by X-ray crystallography, which typically requires a fair amount of trial-and-error and testing many random solution conditions. The Nanoliter Crystallization Facility of the University of Minnesota offers high-throughput screening of crystallization conditions for macromolecular samples to facilitate this process, allowing researchers from UMN and outside institutions to efficiently conduct a large number of crystallization trials with low sample consumption. The facility features robotics to set up small-volume crystallization experiments and an automated imaging system for convenient online tracking of the results. This approach enhances the probability of obtaining high-quality crystals suitable for structure determination. Furthermore, we have ongoing efforts to develop an automated scoring system for crystal identification, which aims to streamline the crystallization workflow and further enhance overall efficiency in crystal screening and evaluation.
To date, the facility has served more than 50 laboratories and contributed to various research projects targeting such diverse public health problems as Alzheimer’s disease, bioterrorism, bacterial pathogens, blood clotting, bone development, calcium homeostasis, cancer, chronic pain, contraception, diabetes, hemochromatosis, HIV, Huntington disease, mitochondrial disorders, muscular dystrophy, obesity, oxalate stones and SARS, resulting in over 200 protein structures deposited in the Protein Data Bank (PDB).