# TR&D Project 3. The Analysis Stage II: Tools for Analyzing the Connectivity and Morphology of Macromolecular Assemblies

> **NIH NIH P41** · ROCKEFELLER UNIVERSITY · 2022 · $69,880

## Abstract

PROJECT SUMMARY
TR&D Project 3. The Analysis Stage II: Tools for Analyzing the Connectivity and Morphology of
Macromolecular Assemblies
As the structure of an assembly is directly related to its functional role, we aim to define the architecture of
isolated native macromolecular complexes of interest. For this, our molecular microscope pipeline needs
information on the shape and connectivity of an assembly’s components, accurately representing their
arrangement at the highest spatial and temporal resolution. Thus, we will develop and refine methodologies to
determine the morphologies and spatial relationships between components within complexes at several distance
scales, ranging from a description of the overall subunit shape and arrangement to defining atomic resolution
contacts between pairs of macromolecules. Our strategy entails using orthologous methods, in order to provide
complementary data and to cover a wide range of resolutions, to inform us about the shape, dimensions and
connectivity of single proteins and macromolecular assemblies. We will focus on methods that have already
proven particularly empowering, but which have significant scope for further advancement. These include
electron microscopy (EM) and chemical cross-linking with mass spectrometry (XL-MS): through the former, we
can produce morphological maps with sufficient detail to resolve the shapes and locations of complexes,
proteins, domains and folds; in parallel, through the latter, we will obtain information on how each component of
the assembly is positioned relative to all other components, and the entire structure. These data when combined
with data from complementary, well-established methods, will be used to generate structural models of
assemblies. To elucidate cellular functions, we propose to gather and interpret dynamic data about the changing
morphologies of assemblies, and the changing interactions within these assemblies. Our molecular microscope
pipeline thus seeks to build concrete high precision 3D models, and 4D models that change in time.

## Key facts

- **NIH application ID:** 10401762
- **Project number:** 5P41GM109824-09
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** Brian T Chait
- **Activity code:** P41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $69,880
- **Award type:** 5
- **Project period:** 2014-08-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10401762

## Citation

> US National Institutes of Health, RePORTER application 10401762, TR&D Project 3. The Analysis Stage II: Tools for Analyzing the Connectivity and Morphology of Macromolecular Assemblies (5P41GM109824-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10401762. Licensed CC0.

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