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 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

    • 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 02/12/2024

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 February and March 2024. 

    February 2024 Soluble (in progress)

    • Reservation Deadline: Fri Feb 9th
    • Package Acceptance & Plate Setup:
      • Tues Feb 13th – Thurs Feb 15th
      • Tues Feb 20th – Thurs Feb 22nd

    March 2024 Soluble (taking reservations)

    • Reservation Deadline: Fri Mar 1st
    • Package Acceptance & Plate Setup:
      • Tues Mar 6th – Thurs Mar 8th
      • Mon Mar 12th – Thurs Mar 15th
      • Mon Mar 19th – Thurs Mar 22nd

    Note  samples are not set up on Fridays.

    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.

    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

    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. Lynch is a quantitative and computational scientist focused on applications in structural biology and image analysis. Her work focuses on how we can use imaging methods to better detect and characterize samples for structural biology techniques. She received her PhD from University of Rochester on Bayesian methodology, and continued to a postdoctoral fellowship at Harvard TH Chan School of Public Health on modeling methods for HIV disease progression. Besides developing quantitative methods to make better use of imaging for crystal growth and detection in the HTX Center, she also pursues computational approaches for understanding protein motion from structural data.

     

    Dr. Gabby Budziszewski: Operations Manager

    Dr. Budziszewski is a native Buffalonian who completed her bachelor’s in biochemistry at Canisius College prior to moving to the University of North Carolina to complete her PhD in Biochemistry & Biophysics at the University of North Carolina at Chapel Hill working in the McGinty lab. She has expertise in macromolecular crystallography, recombinant protein expression and purification, enzymology, and biochemical assay development. She joined the HTX Center in Fall 2022.  Dr. Budziszewski is passionate about working with users to develop strategies to produce diffraction-quality crystal hits and promoting an inclusive scientific work environment.

     

    Elizabeth Snell: Research Associate

    Elizabeth Snell has more than 15 years of experience in protein crystallization. Several of the proteins that she has worked on have flown on the International Space Station, and she is currently working on developing a pipeline to provide optimization of crystallization results to HTX Center users. She received her B.S. in Chemistry from the University of Alabama in Huntsville.

     

    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).

    User Announcements

    Sample Submission Form - Technical Difficulties (February 2024)

    We are having technical difficulties with the ReCaptcha on the web form for submission.  We are working on a solution.

    Please continue to submit your sample information web form when you ship sample(s), and make sure to email us at htslab@hwi.buffalo.edu with the shipment tracking number, the number of samples you have shipped, and that you have submitted form(s) online.  We are able to retrieve the form so please only submit one form for each sample. We will verify that we have received the sample(s) and the form information once the sample(s) arrive.

    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:

          •      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

    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

    getacrystal.org
    Follow us on Mastadon: @getacrystal@mstdn.science