# Structural Biology Core

> **NIH NIH U54** · SEATTLE CHILDREN'S HOSPITAL · 2022 · $991,810

## Abstract

ABSTRACT, CORE 2
Deciphering the molecular mechanisms underlying key steps of the HIV-1 replication cycle is essential to fully
describe the biology of the virus, its interplay with host components, and for developing novel antiretroviral
therapies. Toward this goal, structural biology plays an important role, as an atomic-level understanding of
macromolecular structure and dynamics, and how alterations in structure affect function, provides mechanistic
insights into the workings of biological macromolecules. The structural biology core (Core 2) will contribute
complementary expertise, instrumentation, and resources for studying key steps of the viral replication cycle, as
described within individual projects, including viral entry/uncoating, integration, and maturation/assembly.
Core 2 includes: hydrogen deuterium exchange coupled to mass spectrometry (HDX-MS) and cross-linking mass
spectrometry (XL-MS), nuclear magnetic resonance (NMR) spectroscopy, single-particle cryo-electron
microscopy (cryo-EM), and cryo-electron tomography (cryo-ET). HDX-MS and XL-MS methods have emerged
as powerful tools to probe protein interactions with ligands, co-regulatory proteins, and nucleic acids in solution
to yield insights into macromolecular behavior on a residue-by-residue level. NMR spectroscopy enables
determining high-resolution structures of small-to-medium size proteins and nucleic acids, probing
macromolecular interactions at atomic resolution and studying conformational dynamics. Single-particle cryo-
EM yields an understanding of macromolecular structure and dynamics for large assemblies, often with less
material and more rapidly than with traditional methods. Cryo-ET and sub-tomogram averaging (STA) is ideally
suited to studying irregular objects such as non-icosahedral protein lattices, where having 3D volumetric
information for each unique assembly, prior to ensemble averaging, is necessary to gain insight into local and
long-range structural perturbations.
Core 2 will apply existing tools to address specific questions described within individual Projects, and each
laboratory will also develop novel technologies to meet the needs of proposed research goals. The Core has
established collaborations with most current B-HIVE investigators, has developed workflows for new projects
that may emerge during the studies, and will provide ongoing consultation and training to B-HIVE members as
projects develop. The established tools provide complementary and synergistic expertise toward the broad
research goals of the center, while the training and dissemination module aligns with the broader impacts of the
NIH.

## Key facts

- **NIH application ID:** 10508447
- **Project number:** 1U54AI170855-01
- **Recipient organization:** SEATTLE CHILDREN'S HOSPITAL
- **Principal Investigator:** Dmitry Lyumkis
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $991,810
- **Award type:** 1
- **Project period:** 2022-06-22 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10508447

## Citation

> US National Institutes of Health, RePORTER application 10508447, Structural Biology Core (1U54AI170855-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10508447. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*