The High-Throughput Crystallization Screening Center
The Crystallization Center supports industry, academic, government, and non-profit research institutes, providing unique protein crystallization services for structural biology. Our methods have generated lead crystallization conditions for approximately half of all samples submitted and provided solubility phase information across 1,536 different chemical conditions – information that can guide optimization and troubleshoot recalcitrant systems. Since it began operations in February 2000, the Crystallization Center has set up over 25 million crystallization experiments on more than 18,000 biological macromolecules for almost 2,000 laboratories worldwide. Macromolecular crystallization services at HWI enable experiments that are monitored with state-of-the-art imaging techniques, empowering the detection of crystals that other techniques miss. Our academic, government, and non-profit services are subsidized by NIH and NSF support.
Crystallization Screening at HWI provides:
- Expert staff – Dr. Sarah Bowman has been Director of the HTX Center for over three years and works with scientific staff that have been operating the Center for close to two decades.
- State-of-the-art instrumentation – Brightfield (visual), second-order harmonic, and UV-two photon excited fluorescence techniques in a Rock Imager 1000 with SONICC are used, so no crystal is missed.
- Timely access – Runs are scheduled in advance on a monthly basis with multiple setup windows.
- A history of success – The Center has worked with academic, non-profit, government and industry users, and has screened over 18,000 proteins for close to 2,000 laboratories worldwide.
- Confidentiality – Information will not be publicly disclosed regarding any sample received for crystallization trials without the express written consent of the investigator(s).
Information for Upcoming Crystallization Screening
As the COVID-19 pandemic continues, the HWI Crystallization Center is active and able to support your scientific efforts, both on COVID-19 related projects and the crystallization of other targets. We are running two separate two week runs for March!
March 2021 Soluble Run #1
- Reservation Deadline: Friday March 5th
- Package Acceptance: Tues March 9th – Thurs March 18th
- Plate Setup:
- Tues March 9th – Thurs March 11th
- Mon March 15th – Thurs March 18th
March 2021 Soluble Run #2
- Reservation Deadline: Friday March 19th
- Package Acceptance: Tues March 23rd – Wed March 31st
- Plate Setup:
- Tues March 23rd – Thurs March 25th
- Mon March 29th – Wed March 31st
Note: Samples are not set up on Fridays.
Get a Crystal:
How It Works
Check the run schedule and reserve a spot in the queue for an upcoming high-throughput crystallization screening run (see the buttons above).
1,536 non-redundant crystallization conditions are used to screen your sample using the microbatch-under-oil method, providing an efficient sampling of chemical parameter space. Each condition is imaged using state-of-the-art Formulatrix Rock Imagers over a period of six weeks. Imaging modalities include visual (brightfield) and Second-Order Non-linear Imaging of Chiral Crystals (SONICC), which includes Second Harmonic Generation (SHG) and UV-Two Photon Excited Fluorescence (UV-TPEF) imaging. SHG and UV-TPEF imaging can identify biological crystals not picked up visually or those obscured by precipitate. Brightfield, SHG, and UV-TPEF images are integrated with analysis software provided as part of the crystallization screening service.
Citing the Crystallization Center
NIH and NSF funding enables us to provide efficient high-throughput crystallization screening to academic, non-profit and government laboratories at a reduced rate.
For non-SARS-CoV-2 samples, we request that our current NIH grant is acknowledged in any publications. We suggest the following language: Crystallization screening at the HTX Center at HWI was supported through NIH grant R24GM12135.
For SARS-CoV-2 samples, we currently have NSF RAPID funding. If making use of this funding resource, we request that the NSF grant is acknowledged in any publications. We suggest the following language: Crystallization screening at the HTX Center at HWI was supported through NSF grant 2029943.
Additionally, it would be helpful if the experimental methods references the Crystallization Center using this reference: Luft, J. R., et al. (2003). A deliberate approach to screening for initial crystallization conditions of biological macromolecules. J. Struct. Biol. 142, 170-179. This will help us to secure future funding for the Crystallization Center.
The Crystallization Center Produces Results
Crystals of the Month February 2021! Oak Ridge National Laboratory researchers Daniel Kneller, Andrey Kovalevsky & team have been at the heart of the fight against COVID-19. A gallery of structures of the heart-shaped main protease solved by the ORNL researchers, superimposed on flower-like crystals of the protein grown at the Crystallization Center.
The Crystallization Center has been a resource for structural biology providing enhanced high-throughput crystallization screening for SARS-CoV-2 protein samples. Dr. Sarah Bowman gave a lightning talk update on our progress at the COVID Commons with the Northesat Big Data Innovation Hub! We are providing crystallization screening experiments through our NSF RAPID funding.
Summer intern Ethan Hollerman won a Student Poster Prize at the 2020 LCLS/SSRL Users' Meeting for his work on implementing the MARCO algorithm into a new GUI! MARCO POLO is a multi-platform open-source Python-based graphical user interface that has been developed to provide access to MARCO automated classification and data management tools for biomolecular crystallization screening. MARCO is an academic and industry collaboration using image data from the Crystallization Center, Bristol-Myers...
Crystal structures of AztD from pathogenic bacteria by Crystallization Center user Professor Erik Yukl and team reveal mechanistic insights into zinc transfer! Initial crystal hits were obtained in the Crystallization Center and were optimized by the investigators using hanging drop vapor diffusion and microbatch under oil. High resolution diffraction data collected at the Advanced Light Source. Neupane, DP, et al. Crystal structures of AztD provide mechanistic insights into direct zinc...
The COVID-19 disease caused by the SARS-CoV-2 coronavirus has become a pandemic health crisis. An attractive target for antiviral inhibitors is the main protease 3CL Mpro due to its essential role in processing the polyproteins translated from viral RNA. The Crystallization Center worked with samples from Oak Ridge National Laboratory to help a study on room temperature X-ray structure of unliganded SARS-CoV-2 3CL Mpro. Inital crystal hits helped the researchers determine the ligand-free...
Transforming growth factor -1 (TGF-1) is a secreted signaling protein that directs many cellular processes and is an attractive target for the treatment of several diseases. This study looks at the regulatory mechanism of TGF-1 and is of fundamental importance for therapeutic development. Initial crystal hits were obtained from the Crystallization Center and X-ray data were collected on the IMCA beamline at the Advanced Photon Source. The study was published in a paper entitled “Structural...
Mutations in ABC subfamily C member 6 (ABCC6) transporter are associated with pseudoxanthoma elasticum, a disease resulting in ectopic mineralization and affecting multiple tissues. The Thibodeau Group recent paper explores these mutations. Crystallization screening of multiple proteins took place in the Crystallization Center with hits being optimized by the authors using sitting-drop vapor diffusion methods. Crystallographic data was collected on a Rigaku FR-E Superbright rotating anode...
Publications Citing the Crystallization Center
Crystallization Center Staff
Dr. Sarah EJ Bowman: Director
Dr. Bowman has been working in structural biology for over 15 years. She did her PhD research at University of Rochester in the Bren Lab. She then moved to Massachusetts Institute of Technology for postdoctoral research in the Drennan and Stultz Groups (supported by an NIH Ruth L. Kirschstein NRSA fellowship), followed by a second postdoctoral appointment at Los Alamos National Laboratory. She joined HWI in July 2017.
Angela Lauricella: Research Technician (18+ years)
Stephen Potter: Director of Information Technology (20+ years)
Nate Michals: System Administrator
MARCO Polo Image Viewing GUI
We are excited to announce that the new GUI for automated crystal hit scoring is available to users! MARCO Polo currently works with the high-throughput 1,536 screening metadata and images from the Crystallization Center. It is open-source and we would love to collaborate on making MARCO more available to crystallographers everywhere!
MacroscopeJ & macOS Upgrades
The new version of MacroscopeJ is compatible with Catalina macOS and is in your ftp folder when you transfer images – please let us know if you have any issues!
Please note that macOS 11.0 ‘Big Sur’ is due out this year, and will have entirely new hardware architecture. We recommend that users hold off on upgrading to macOS 11.0 immediately so that we can update our software accordingly.
Accessing your images via the ftp server
Because of recent changes for both Mac and Windows OS, we recommend using FileZilla to access and transfer imagers from the ftop servers, as it works across platforms.
For more details: Analyze Your Results
High-Throughput Crystallization Screening Center
Hauptman-Woodward Medical Research Institute
700 Ellicott Street
Buffalo, NY 14203