National High-Throughput Crystallization Center
The HWI Crystallization Center has been awarded NIH NIGMS funding to become a National Resource for crystallography. As the National High-Throughput Crystallization Center, we support academic, government, and non-profit research institutes and industry, 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 directing the Center since being recruited to HWI in 2017 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
Deadlines and Dates
Updated 05/10/2022
The HWI National High-Throughput Crystallization Center is active and able to support your crystallization efforts. We are happy to announce a 3 week soluble protein run in May & June. Happy Crystallizing!
May 2022 Soluble (in process)
- Reservation Deadline: Fri May 6th
- Package Acceptance: Tues May 10th to Thurs May 26th
- Plate Setup:
- Tues May 10th – Thurs May 12th
- Mon May 16th – Thurs May 19th
- Mon May 23rd – Thurs May 26th
- Tues May 10th – Thurs May 12th
June 2022 Soluble (taking reservations)
- Reservation Deadline: Fri June 10th
- Package Acceptance: Tues June 14th to Thurs June 30th
- Plate Setup:
- Tues June 14th – Thurs June 16th
- Mon June 20th – Thurs June 23rd
- Mon June 27th – Thurs June 30th
- Tues June 14th – Thurs June 16th
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. Click here to access the current crystallization cocktail lists.
Reminder to Acknowledge the National High-Throughput Crystallization Center and Funding Agencies
We are grateful that NIH and NSF funding enables us to provide efficient high-throughput crystallization screening to academic, non-profit and government laboratories at a reduced rate. Please remember to cite the appropriate grant funding for your crystallization screening experiments.
- For non-SARS-CoV-2 samples, we request that the NIH R24 National Resource grant is acknowledged in any publications. Please note that with the new funding, the NIH grant number is now R24GM141256. We suggest the following language: Crystallization screening at the National Crystallization Center at HWI was supported through NIH grant R24GM141256.
- For SARS-CoV-2 samples, NSF RAPID funding was available for users through April 2022. If your lab made 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 National Crystallization Center at HWI was supported through NSF grant 2029943 and NIH grant R24GM141256.
Additionally, it would be helpful if the experimental methods references the Crystallization Center using this reference for the soluble screen: Luft, J. R., et al. (2003). A deliberate approach to screening for initial crystallization conditions of biological macromolecules. J. Struct. Biol. 142, 170-179.
For the membrane screen, please cite this reference: Koszelak‐Rosenblum, M., et al. (2009). Determination and application of empirically derived detergent phase boundaries to effectively crystallize membrane proteins. Protein Science, 18(9), 1828-1839.
These citations help us to track publications and PDB depositions, an important metric of productivity that will help secure future funding for the Crystallization Center.
The Crystallization Center Produces Results
Featuring our new crystal hunting software - MARCO Polo! Explore your crystallization parameter space with MARCO Polo! Open-source and on GitHub - available to download: https://hauptman-woodward.github.io/Marco_Polo/ MARCO Polo implements the MAchine Recognition of Crystallization Outcomes (MARCO) and interfaces directly with our high-throughput 1,536 crystallization screening images and metadata from the Crystallization Center. Great work by NSF BioXFEL STC summer research intern Ethan...
March 2021 Crystals of the Month
Crystals of the Month March 2021! Celebrating the Crystals of the Month with nanolipoprotein crystallization from Megan Shelby and team at LLNL! Always great to see results from Crystallization Center users! Link to paper: https://mdpi.com/844698
February 2021 Crystals of the Month
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.
SARS-CoV-2 protein crystallization screening!
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.
MARCO Polo: Finding Crystals
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...
Mechanistic insights into zinc transfer
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...
Supporting SARS-CoV-2 Research
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...
Structural insights into latency-associated peptide and TGFβ-1
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...
Structural analysis of the ABCC6 transporter
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
National Crystallization Center Team
Dr. Sarah EJ Bowman
Dr. Sarah EJ Bowman: Director
Dr. Bowman has been working in structural biology for over 15 years. She completed 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 the Crystallization Center at HWI in July 2017.
Angela Lauricella
Elizabeth Snell
In the Lab:
Angela Lauricella:
Research Technician at the Crystallization Center for 18+ years
Elizabeth Snell:
Research Associate at the Crystallization Center with 15+ years of experience
Computational Support:
Stephen Potter: Director of Information Technology
Nate Michals: Systems Administrator
Crystals of the Month March 2022!
Excited to feature a recent publication by HTX Center users in the Izard Lab at Scripps as Crystals of the Month!
‘We used over 1000 commercially available crystallization screens … to attempt to grow … crystals but our efforts were unsuccessful. Thus, we resorted to the high-throughput crystallization screening facility at the Hauptman-Woodward Medical Research Institute. Out of the 1536 crystallization conditions that were screened, crystals appeared from 500 mM imidazole (pH 6.5) and 15% (w/v) polyethylene glycol 3350 using the micro batch-under-oil method. We adapted this condition from the micro batch-under-oil method for hanging drop vapor diffusion … to grow crystals that diffracted X-ray beyond 1.6 Å Bragg spacings.‘
Check out the paper: https://doi.org/10.1016/j.mbplus.2021.100074
COVID Information Commons Talk
Recent talk by Center Director Dr. Bowman at COVID Information Commons about the NSF RAPID funded work we are doing in the National High-Throughput Crystallization Center!
Check it out on YouTube!
User Announcements
Updates to Email Announcement List (May 2022)
We are planning an upgrade to a new mail list server in June – stay tuned for details!
MARCO Polo & macOS Upgrades (May 2022)
Please note that we are still testing new macOS options for MARCO Polo for Monterey MacOS. Both image viewing software GUIs work with macOS Catalina and Big Sur, but if you are having trouble with installation, let us know – we can walk through troubleshooting with solutions we’ve found work.
MARCO Polo Image Viewing GUI (April 2021)
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!
Open-source and on GitHub – available to download: https://hauptman-woodward.github.io/Marco_Polo/
MARCO Polo implements the MAchine Recognition of Crystallization Outcomes (MARCO) and interfaces directly with our high-throughput 1,536 crystallization screening images and metadata from the Crystallization Center.
Supported by NSF BioXFEL STC Grant Number 1231306, NSF BIO 2029943, NIH R24 GM124135
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 images from the ftp servers, as it works across platforms. Alternatively, use the MARCO Polo ftp download option!
For more details: Analyze Your Results
Physical address
National High-Throughput Crystallization Center
Hauptman-Woodward Medical Research Institute
700 Ellicott Street
Buffalo, NY 14203
Contact
General Inquiries: htslab@hwi.buffalo.edu
National Crystallization Center Director (Dr. Sarah EJ Bowman): sbowman@hwi.buffalo.edu
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