High-Throughput Crystallization Screening Center | Hauptman-Woodward Medical Research Institute

National Crystallization Center

The HWI Crystallization Center has been awarded NIH NIGMS funding to become a National Resource for crystallography. As the National 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 9/28/2021

The HWI National 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 in the final week of the September soluble screen. In October we will have an extended soluble run, and are planning ahead for the November run. Stay tuned for the next membrane run, as well.

October 2021 Soluble

Reservation Deadline: Mon October 11th
Package Acceptance: Wed October 13th to Thurs October 28th
Plate Setup:
- Wed October 13th – Thurs October 14th
- Mon October 18th – Thurs October 21st
- Mon October 25th – Thurs October 28th

November 2021 Soluble

Reservation Deadline: Fri November 5th
Package Acceptance: Tues November 9th to Thurs November 18th
Plate Setup:
- Tues November 9th – Thurs November 11th
- Mon November 15th – Thurs November 18th

Note: Samples are not set up on Fridays.

Get a Crystal:

Academic, Government & Non-Profit Institutes

Proprietary Samples: Industry Liaison Information

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 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, 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 National Crystallization 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 track publications, an important metric of productivity that will help secure future funding for the Crystallization Center.

The Crystallization Center Produces Results

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...

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

In the Lab:

Angela Lauricella:

Research Technician at the Crystallization Center for 18+ years

Computational Support:

Stephen Potter: Director of Information Technology

Nate Michals: Systems Administrator

HWI Co-Investigators:

Dr. Miranda L Lynch

Dr. Eddie Snell

We are hiring at the National Crystallization Center! To find out more, see the Careers at the Institute page.

Celebrating Crystal Imaging with New Software!

This month we are featuring our new crystal hunting software – MARCO Polo! Explore your crystallization parameter space with MARCO Polo! It 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 Holleman, who started on this idea while interning at IMCA-CAT at APS with Lisa Keefe and Erica Duguid, and created the GUI during the summer of 2020 working with Sarah Bowman. The Polo paper is out! Holleman, ET, et al. (2021) Polo: an open-source graphical user interface for crystallization screening. J. Appl. Cryst. 54, 673-679.

MARCO Polo is open-source and on GitHub! Available for download: https://hauptman-woodward.github.io/Marco_Polo/

Supported by NSF BioXFEL STC Grant Number 1231306, NSF BIO 2029943, NIH R24 GM124135

User Announcements

MARCO Polo, MacroscopeJ & macOS Upgrades (August 2021)

Please note that we are still testing macOS 11.0 ‘Big Sur’ for both MARCO Polo and MacroscopeJ. Both image viewing software GUIs work with macOS Catalina, but if you are having trouble with installing on Big Sur, we are working on it! In the meantime, you may need to use a computer with an earlier OS.

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!

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 ftp servers, as it works across platforms.

For more details: Analyze Your Results