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, 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 support.
Crystallization Screening at HWI provides:
- Expert staff – Dr. Sarah EJ Bowman has been directing the Center since being recruited to HWI in 2017 and works with a growing team of scientists that have been doing structural biology 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).
News from the HTX Center
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- Announcing the Summer 2024 Applied Crystallization Workshop! A one-day virtual workshop, and two 1.5 day on-site workshops to help you with your crystallization projects. Click here for more details, to register and to apply.
- New paper and video out in Journal of Visualized Experiments highlighting the experimental protocols in the HTX Center.
- New paper out in Acta D describing the HTX Center operations.
Information for Upcoming Crystallization Screening
Deadlines and Dates
Updated 04/22/2024
The National High-Throughput Crystallization Center is active and able to support your crystallization efforts. We are happy to announce the upcoming runs for the soluble screen in May & June.
May 2024 Soluble (taking reservations)
- Reservation Deadline: Fri May 3rd
- Package Acceptance & Plate Setup:
- Tues May 7th – Thurs May 9th
- Mon May 13th – Thurs May 16th
- Tues May 7th – Thurs May 9th
June 2024 Soluble (taking reservations)
- Reservation Deadline: Fri May 31st
- Package Acceptance & Plate Setup:
- Tues June 4th – Thurs June 6th
- Mon June 10th – Thurs June 13th
- Tues June 4th – Thurs June 6th
Notes: 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 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.
- We request that the NIH R24 National Resource grant is acknowledged in any publications. We suggest the following language: Crystallization screening at the National Crystallization Center at HWI was supported through NIH grant R24GM141256.
Additionally, it would be helpful if the experimental methods references the Crystallization Center using one of the updated references for the soluble and membrane screens.
- Lynch, ML, Snell, ME, Potter, SA, Snell, EH & Bowman, SEJ (2023). 20 years of crystal hits: progress and promise in ultrahigh-throughput crystallization screening. Acta Cryst. D79, 198-205.
- Budziszewski, GR, Snell, ME, Wright, TR, Lynch, ML & Bowman, SEJ (2023). High-Throughput Screening to Obtain Crystal Hits for Protein Crystallography. J. Vis. Exp. (193), e65211.
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
20 years of crystal hits
A paper entitled 20 years of crystal hits: progress and promise in ultrahigh-throughput crystallization screening by Miranda L. Lynch, M. Elizabeth Snell, Stephen A. Potter, Edward H. Snell, Sarah E. J. Bowman has been published in Acta Cryst D. Volume 79, pages 198-205. The paper notes that diffraction-based structural methods contribute a large fraction of the biomolecular structural models available, providing a critical understanding of macromolecular architecture. However, these methods...
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!
Crystals of the Month March 2022!
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...
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...
Publications Citing the Crystallization Center
National Crystallization Center Team
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 theDrennan and Stultz Groups (supported by an NIH Ruth L. Kirschstein NRSA fellowship), followed by a second postdoctoral appointment at Los Alamos National Laboratory. Dr. Bowman joined the Crystallization Center as the Director in July 2017. She is the PI of the NIGMS National Resource grant funding the HTX Center. Her research group is working to develop new methods that combine crystallographic and spectroscopic approaches to answer fundamental questions about protein biochemistry, especially in metalloproteins.
Dr. Miranda Lynch: Co-Investigator
Dr. Gabby Budziszewski: Operations Manager
Elizabeth Snell: Research Associate
Tiffany Wright: Research Associate
Tiffany Wright joined the Crystallization Center at HWI in November 2022. New to the area of structural biology, she brings her experience to the lab from her background as a B.S. in Forensic Chemistry from Buffalo State College. Her work focuses on high-throughput protein crystallization, and she maintains daily operations and service output in the HTX Center.
Computational Support:
Stephen Potter: Director of Information Technology
Nate Michals: Systems Administrator
Celebrating Crystals of the Month!
Crystals of the Month Nov 2022!
MicroED structure of Dynobactin A from a recent paper just published in Nature Microbiology (https://rdcu.be/cWmNJ).
Applied Crystallization Workshop (April 2024)
We are excited to announce an Applied Crystallization Center Workshop in 2024! Click here for more details.
Does your macromolecular crystallization project feel like the Wild West?
Join our two-part Crystallization Workshop to learn to wrangle your crystals!
What is it? A macromolecular crystallization workshop
- One day virtual component in May 2024 (registration link:https://us06web.zoom.us/meeting/register/tZclfuGpqDgvHNZNhBxWgGA2wT4zdd5AuDsW)
- Two separate 1.5 day on-site components in June or August 2024 (application link: https://forms.gle/y1BYJazpY5gsMoj9A)
Who is it for? Open to researchers at all levels: students, postdocs, PIs
Favored applicants for on-site workshop will have submitted samples for high-throughputscreening prior to the virtual workshop and have a sample to bring to set up.
Deadlines:
Applications for the June 20-21 workshop must be submitted by May 6th, 2024
Applications for the August 20-21 workshop must be submitted by July 8th, 2024
For the on-site portion of the workshop, applicants must be available to travel on-site to Buffalo, New York during the dates of June 20-21, 2024 OR August 20-21, 2024. On-site workshop spaces are limited and applicants will be selected based on suitability of project and application. Note some travel support is available for researchers at US-based universities.
Workshop supported by NIH R24GM141256. We gratefully acknowledge the workshop sponsors MiTeGen, Hampton Research and Formulatrix.
Sample Submission Form - Technical Difficulties (February 2024) - Resolved
These issues have been resolved.
We are having technical difficulties with the ReCaptcha on the web form for submission.
Thank you.
Meritorious User Program (January 2024)
We are very excited to announce the second application deadline for the Meritorious User Program, which will provide reduced cost access to our 1536-well microbatch crystallization screening experiments for crystal screening!
Who qualifies? Faculty, postdocs, and students doing research:
- At primarily undergraduate institutions
- At minority service institutions
- In under-resources or under-funded labs (definition: currently, and for at least the most recent 6 month from application date, without any form of funding stream in excess of $25,000)
For more details: click here
To apply: click here
Next application deadline: Friday, March 15 2024
Marco Polo on Macs (August 2023)
The newset version of Marco Polo(Polo Version 0.2.0) works on Apple Silicon chips!
Click here to download the most recent version!
New Lower Sample Volume Requirements (April 2023)
We have started using the new SPT Labtech Mosquito to deliver sample to the 1536 microassay plates.
What does this mean for users sending samples?
Only 375 microL sample is required to set up the full plate – down from the previously required 500 microL sample.
If you have any questions, please email us at htslab@hwi.buffalo.edu.
National Crystallization Center User's Meeting! (March 2023)
The meeting is scheduled on Friday 3/31/2023 from 10am-3pm (Eastern).
The HTX Center Virtual User Meeting was a great success! We are converting the videos to be posted on YouTube – stay tuned!
Archived User Announcements (2022 & 2021)
Updates to Email Announcement List (August 2022)
We have recently updated our email user list server! Want to sign up to receive emails with upcoming reservations deadlines and updates from the HTX Center?
Sign up by sending an email to crystallization-subscribe@chtsb.org with a blank subject line, then respond to the confirmation email to successfully add your email to the list. If you have any difficulties, please reach out to us at htslab@hwi.buffalo.edu.
Shipping Reminders (July 2022)
We’ve been observing a lot of delays from FedEx shipping, so wanted to post some reminders about shipping samples (especially during the heat of summer!).
1) Send the protein in a clearly labeled 1.5 ml eppendorf tube placed inside of a protective container (such as a Falcon tube).
2) For shipping, we make the following recommendations:
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- Ship on Monday-Wednesday to reduce the risk of a weekend delivery delay.
- Use an insulated Styrofoam shipping container.
- Use dry ice for frozen samples.
- Use gel packs to maintain 4°C or 23°C sample temperatures.
- Send the tracking number to htslab@hwi.buffalo.edu
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Given the delays we’ve been seeing, we are also encouraging you to make sure that your sample has enough ice or dry ice to last for 2+ days. Also, we’ve noticed that shipping via FedEx Priority Overnight (as opposed to Standard Overnight) has a better chance of getting the samples to us by the next day. Please keep an eye on the tracking information on your end, as well, as sometimes a phone call to FedEx from the sender can expedite sample delivery.
MARCO Polo Updates
June 2022
Please note that we are still testing new macOS options for MARCO Polo for Monterey MacOS with the M1 chips. Both image viewing software GUIs work with macOS Catalina, Big Sur, and Monterey with Intel chips, but if you are having trouble with installation, let us know – we can walk through troubleshooting with solutions we’ve found work.
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
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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