# Administrative Supplement for Structural Dynamics in Biology Resource Year 2

> **NIH NIH P41** · STANFORD UNIVERSITY · 2023 · $189,039

## Abstract

Project Summary – Administrative Supplement Request – 1P41GM139687-02 – Sebastien
Boutet (PI).
This administrative supplement request is driven by overall goals and aims of the Structural
Dynamics in Biology BTRR at SLAC National Accelerator Laboratory. The BTRR is aimed at
enhancing and developing the unique capabilities of the SLAC Linac Coherent Light Source
(LCLS) for biomedical applications. The requested supplement will support a broad user base
and further the goals of the DBPs and the TR&Ds.
By overcoming the limitations of radiation damage at the synchrotron, LCLS has been particularly
impactful in the study of large macromolecular machines that form small crystals with high solvent
content, making them delicate, difficult to cryo-preserve and extremely radiation sensitive. For
example, a major breakthrough was the application of SFX to examine crystals of intrinsic
membrane proteins, such as GPCRs, grown in LCP. GPCRs are the largest group of targets for
drug development, used to treat a wide variety of illnesses (e.g. cancer, cardiovascular disease,
and mental illness). LCLS is also impactful in the study of metalloenzymes, which are critical to
nearly all biological processes and as such represent a rich target space for therapeutics
development. High-resolution structural studies of metalloproteins are particularly challenging at
the synchrotron because the metal centers, especially those that are redox active, are very
susceptible to x-ray induced photoreduction. Further, the ultrafast (~40 fs) x-ray pulses produced
by the LCLS open new possibilities in directly observing dynamic processes involved in
macromolecular function. Moreover, many of the P41-derived developments that enable the rapid
collection of data using multiple small crystals, are applicable both at LCLS and at the synchrotron
to mitigate radiation damage. By expanding the capabilities at LCLS and at the SSRL synchrotron,
the BTRR opens more macromolecular machines to structural characterization, including time-
resolved studies over a wide range of biomedically relevant time scales. Integrating with, and
enhancing the existing programs at SSRL and LCLS, the BTRR will provide support, expertise
and training to the broad biomedical community.
This administrative supplement will enhance and expand the BTRR capabilities that are provided
to general users and to the P41 driving biomedical projects. The acquisition of a high speed x-ray
chopper will fill a critical need of the BTRR for efficient use of SSRL BL12-1 with small crystals
delivered by liquid/crystal injectors and for time-resolved measurements. In addition to achieving
microsecond time resolution, by breaking up the continuous x-ray beam into short pulses, the
chopper ensures crystals delivered by injectors are not destroyed by x-ray damage before they
are fully translated into the x-ray beam position, enabling exposure to unattenuated
monochromatic or pink-beam at BL12-1. In addition, this supplement requests...

## Key facts

- **NIH application ID:** 10833964
- **Project number:** 3P41GM139687-03S1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Sebastien Boutet
- **Activity code:** P41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $189,039
- **Award type:** 3
- **Project period:** 2021-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10833964

## Citation

> US National Institutes of Health, RePORTER application 10833964, Administrative Supplement for Structural Dynamics in Biology Resource Year 2 (3P41GM139687-03S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10833964. Licensed CC0.

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