Tuesday, June 24, 2025 6/24/2025

Technology Development for Biological Imaging with XFELs

Award Number: R01GM117342
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2016
PERIOD OF PERFORMANCE END DATE: 05/31/2025

Group Awards By:

View Award Description

Technology Development for Biological Imaging with XFELs - Project Summary / Abstract Determining the structure and conformational dynamics of large protein complexes as well as other biological nanoparticles at room temperature with near atomic resolution has the potential to greatly impact structural biology and our knowledge of biomolecular function and interactions. A major bottleneck in structural biology is that while many critical cellular functions are performed by membrane proteins, they have proven intractable to structure determination by traditional x-ray crystallography, in which x-ray radiation damage is mitigated by spreading the radiation dose over many molecules in a crystal. Consequently, most membrane protein structures remain unknown to date. While cryo-electron microscopy (cryo-EM) has been successful in obtaining high-resolution structural information from large biomolecules and nanoparticles, it requires freezing of the sample to mitigate electron-induced radiation damage and cryogenic measurement makes it impossible to visualize fast conformational changes. X-ray free electron lasers (XFELs), which produce ultra-short and ultra-bright x-ray pulses, allow us to break this nexus between resolution and radiation damage by utilizing the “diffraction-before-destruction” principle and promise imaging at unprecedented spatio-temporal resolution. Over the last decade since the opening of the world's first XFEL, the Linac Coherent Light Source (LCLS) at SLAC National Accelerator Laboratory, protein structure determination at room temperature to near-atomic resolution by serial- femtosecond nanocrystallography (SFX) has been demonstrated. However, several challenges and limitations remain that need to be addressed to fully utilize the capabilities of these new light sources and the upcoming next generation XFELs for structural biology. The overall objective of this proposal is to enable new science by addressing several of the current technological and methodological challenges in x-ray diffractive imaging of biological samples with XFELs, in particular in the areas of sample preparation for membrane proteins that, generally, suffer from low abundance and/or are hard to crystallize, sample introduction technologies enabling high data acquisition rates, and novel approaches to time-resolved structure determination of membrane proteins. This work will also drastically reduce sample consumption and will increase the diversity of membrane protein and other biological nano- objects that can be studied with XFELs. The proposed work also aims to develop new capabilities for time- resolved structural studies at XFELs to include cross-membrane potential triggered membrane protein dynamics, enabling investigation of a broader range of biomolecular and cellular reactions and the associated structural change over a large range of times scales from microseconds to milliseconds. If successful, this work would greatly aid our experimental capabilities to study and understand function of protein complexes and biological nanoparticles in a wide range of fields including human health and biosecurity.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $526,300 )
2024	2024	LAWRENCE LIVERMORE NATIONAL SECURITY, LLC	2300 1ST ST	LIVERMORE	CA	94550	ALAMEDA	USA	Biomedical Research and Research Training	000	9	5/10/2024	NON-COMPETING CONTINUATION	$526,300
														Subtotal = $526,300

Issue Date FY: 2023 ( Subtotal = $525,739 )
2023	2023	LAWRENCE LIVERMORE NATIONAL SECURITY, LLC	2300 FIRST ST STE 204	LIVERMORE	CA	94550	ALAMEDA	USA	Biomedical Research and Research Training	000	8	5/9/2023	NON-COMPETING CONTINUATION	$525,739
														Subtotal = $525,739

Issue Date FY: 2022 ( Subtotal = $525,335 )
2022	2022	LAWRENCE LIVERMORE NATIONAL SECURITY, LLC	2300 FIRST ST STE 204	LIVERMORE	CA	94550	ALAMEDA	USA	Biomedical Research and Research Training	002	7	6/28/2022	NON-COMPETING CONTINUATION	$525,335
2022	2021	LAWRENCE LIVERMORE NATIONAL SECURITY, LLC	2300 FIRST ST STE 204	LIVERMORE	CA	94550	ALAMEDA	USA	Biomedical Research and Research Training	001	6	4/1/2022	COMPETING CONTINUATION	$112,600
2022	2020	LAWRENCE LIVERMORE NATIONAL SECURITY, LLC	2300 FIRST ST STE 204	LIVERMORE	CA	94550	ALAMEDA	USA	Biomedical Research and Research Training	000	5	4/1/2022	NON-COMPETING CONTINUATION	-$112,600
														Subtotal = $525,335

Issue Date FY: 2021 ( Subtotal = $532,873 )
2021	2021	LAWRENCE LIVERMORE NATIONAL SECURITY, LLC	2300 FIRST ST STE 204	LIVERMORE	CA	94550	ALAMEDA	USA	Biomedical Research and Research Training	001	6	5/13/2021	COMPETING CONTINUATION	$532,873
2021	2020	LAWRENCE LIVERMORE NATIONAL SECURITY, LLC	2300 FIRST ST STE 204	LIVERMORE	CA	94550	ALAMEDA	USA	Biomedical Research and Research Training	000	5	5/13/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $532,873

Issue Date FY: 2020 ( Subtotal = $541,329 )
2020	2020	LAWRENCE LIVERMORE NATIONAL SECURITY, LLC	2300 FIRST ST STE 204	LIVERMORE	CA	94550	ALAMEDA	USA	Biomedical Research and Research Training	000	5	4/1/2020	NON-COMPETING CONTINUATION	$541,329
														Subtotal = $541,329

Issue Date FY: 2019 ( Subtotal = $536,721 )
2019	2019	LAWRENCE LIVERMORE NATIONAL SECURITY, LLC	7000 EAST AVE	LIVERMORE	CA	94550	ALAMEDA	USA	Biomedical Research and Research Training	000	4	2/9/2019	NON-COMPETING CONTINUATION	$536,721
														Subtotal = $536,721

Issue Date FY: 2018 ( Subtotal = $535,786 )
2018	2018	LAWRENCE LIVERMORE NATIONAL SECURITY, LLC	2300 FIRST ST STE 204	LIVERMORE	CA	94550	ALAMEDA	USA	Biomedical Research and Research Training	001	3	5/10/2018	NON-COMPETING CONTINUATION	$53,580
2018	2018	LAWRENCE LIVERMORE NATIONAL SECURITY, LLC	2300 FIRST ST STE 204	LIVERMORE	CA	94550	ALAMEDA	USA	Biomedical Research and Research Training	000	3	2/3/2018	NON-COMPETING CONTINUATION	$482,206
														Subtotal = $535,786

Issue Date FY: 2017 ( Subtotal = $532,205 )
2017	2017	ENERGY LIVERMORE OFFICE, UNITED STATES DEPARTMENT OF	7000 E AVE	LIVERMORE	CA	94550	ALAMEDA	USA	Biomedical Research and Research Training	001	2	8/18/2017	NON-COMPETING CONTINUATION	$53,223
2017	2017	ENERGY LIVERMORE OFFICE, UNITED STATES DEPARTMENT OF	7000 E AVE	LIVERMORE	CA	94550	ALAMEDA	USA	Biomedical Research and Research Training	000	2	2/27/2017	NON-COMPETING CONTINUATION	$478,982
														Subtotal = $532,205

Issue Date FY: 2016 ( Subtotal = $533,280 )
2016	2016	LAWRENCE LIVERMORE NATIONAL SECURITY, LLC	2300 FIRST ST STE 204	LIVERMORE	CA	94550	ALAMEDA	USA	Biomedical Research and Research Training	000	1	4/28/2016	NEW	$533,280
														Subtotal = $533,280

Grand Total All Awards = $4,789,568

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Technology Development for Biological Imaging with XFELs

Award Number: R01GM117342

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/01/2016

PERIOD OF PERFORMANCE END DATE: 05/31/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer