Hauptman-Woodward Medical Research Institute Inc
Biological Sciences (BIO)
An award is made to Hauptman-Woodward Institute to extend its structural biology services for researchers working with SARS-CoV-2 related samples and to accelerate knowledge production about SARS-CoV-2 virus proteins. Structural biology methods help in understanding fundamental principles at the base of how biomolecules work by enabling visualization of those molecules at a high level of detail. Since SARS-CoV-2 emerged as a pathogenic threat in late 2019, structural biology methods have already been critical in providing details about how the virus enters human cells and how viral proteins interact with human proteins. One difficult step in achieving these structural maps is locating experimental conditions that allow the protein samples to be studied, and this project is geared toward addressing that bottleneck. The Crystallization Center provides state-of-the-art robotic equipment and specialized imaging to structural biology researchers worldwide who are studying protein structures. This project will provide immediate access to these resources and enable enhanced services to be developed for researchers working directly with SARS-CoV-2 related samples. This project will also develop new experimental pipelines to accelerate response time in the face of the current and future pandemics. The number of viruses that impact human society continues to rise, as evidenced by recent outbreaks of SARS, MERS, Ebola and Zika virus, among others. Viruses have the potential to damage national health and prosperity, and efforts such as this research therefore have potential to contribute to solutions to these global problems. Since the appearance of the novel pathogen SARS-CoV-2, over 100 structures of viral proteins have been deposited to the Protein Data Bank, including 92 recent depositions of the SARS-CoV-2 main protease in complex with different ligands (as of April 15, 2020). Close to 95% of the structures deposited thus far are derived from macromolecular X-ray crystallography (MX) experiments. One of the major bottlenecks in MX experiments is determining the conditions in which a protein will crystallize, and this hinders the rapid response needed in the current pandemic. The Crystallization Center is a high-throughput crystallization facility that facilitates rapid, efficient crystallization of biomolecular targets and is the only resource in the world available to external users that makes high-throughput crystallization screening accessible with 1,536 conditions in one experimental plate and provides state-of-the-art imaging methods capable of detecting protein crystals very rapidly. These resources are being made available to researchers working with SARS-CoV-2 samples. Additionally, crystallization pipelines are being expanded with 1) increased state-of-the-art imaging in the experimental pipeline, 2) optimization and scale-up experiments at the facility, and 3) expedited crystal sample harvesting and shipping. This project will have a profound impact on the scientific community’s ability to quickly solve SARS-CoV-2 protein structures, facilitating a better understanding of the basic science underlying coronavirus biology.This RAPID award is made by the Division of Biological Infrastructure (DBI) using funds from the Coronavirus Aid, Relief, and Economic Security (CARES) Act.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.