R24GM141256

National HTX Center: Enabling Access to State-of-the-Art Crystallization Capabilities - Project Summary

Structural biology is a field with a goal to delineate the physical architecture of biological macromolecules. A primary structural method employed in this endeavor is macromolecular X-ray crystallography (MX). MX methods account for nearly 90% of the greater than 165,000 structures deposited to the Protein Data Bank. However, a primary challenge to successful MX structure determination is finding conditions in which a macromolecule will crystallize.

To address this obstacle, an arsenal of chemical cocktail screens and high-throughput screening methods, coupled with specialized imaging, have been brought to bear on the problem of determining the conditions in which a macromolecular target will form a crystal that is of sufficient quality to be amenable to X-ray diffraction structure determination.

This proposal focuses on continuing and extending the capabilities of a central resource providing critical high-throughput crystallization screening to the scientific community, the High-Throughput Crystallization Screening Center (HTX) at Hauptman-Woodward Medical Research Institute. The HTX Center has been in operation for two decades, providing a unique national crystallization resource specifically geared to help overcome the obstacle of coaxing a macromolecule to crystallize.

The HTX Center provides a high-throughput screening format designed to minimize sample requirements via the use of small volume liquid-handling robotics, a unique experimental set-up, and state-of-the-art imaging for screening. Notably, the technologies, instruments, and expertise available at the HTX Center are not widely available.

This proposal focuses on extending the capabilities of the HTX Center by developing an expanded repertoire of experimental screening options and improved image analysis and processing, while performing instrumentation upgrades to maintain the HTX Center as a premier resource for crystallization screening for the scientific user community.

We propose developing and implementing the necessary computational infrastructure and software to accommodate new screening plate definitions and optimization of successful crystallization hits, and improved user interfaces to maximize the information accessibility from screening experiment outcomes.

A major goal of this proposal is to increase access to the state-of-the-art crystallization screening instrumentation and expertise to researchers from a wide array of laboratories in academic, non-profit, and government institutes. The objective is to ensure access that enables a broad range of biomedically important research.

Hauptman Woodward Medical Research Institute

THE NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES (NIGMS) SUPPORTS BASIC RESEARCH THAT INCREASES OUR UNDERSTANDING OF BIOLOGICAL PROCESSES AND LAYS THE FOUNDATION FOR ADVANCES IN DISEASE DIAGNOSIS, TREATMENT, AND PREVENTION. NIGMS ALSO SUPPORTS RESEARCH IN SPECIFIC CLINICAL AREAS THAT AFFECT MULTIPLE ORGAN SYSTEMS: ANESTHESIOLOGY AND PERI-OPERATIVE PAIN, CLINICAL PHARMACOLOGY ?COMMON TO MULTIPLE DRUGS AND TREATMENTS, AND INJURY, CRITICAL ILLNESS, SEPSIS, AND WOUND HEALING.? NIGMS-FUNDED SCIENTISTS INVESTIGATE HOW LIVING SYSTEMS WORK AT A RANGE OF LEVELSFROM MOLECULES AND CELLS TO TISSUES AND ORGANSIN RESEARCH ORGANISMS, HUMANS, AND POPULATIONS. ADDITIONALLY, TO ENSURE THE VITALITY AND CONTINUED PRODUCTIVITY OF THE RESEARCH ENTERPRISE, NIGMS PROVIDES LEADERSHIP IN SUPPORTING THE TRAINING OF THE NEXT GENERATION OF SCIENTISTS, ENHANCING THE DIVERSITY OF THE SCIENTIFIC WORKFORCE, AND DEVELOPING RESEARCH CAPACITY THROUGHOUT THE COUNTRY.

93.859 - Biomedical Research and Research Training

National Institute of General Medical Sciences (NIGMS) [HHS - NIH]

New York United States

State-Wide

Limited Competition: NIGMS National and Regional Resources (R24 - Clinical Trial Not Allowed) (PAR-19-301)

Amendment Since initial award the End Date has been shortened from 06/30/26 to 01/02/25 and the total obligations have increased 357% from $1,092,597 to $4,998,556.