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

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.

Here we will develop and refine methodologies to determine the morphologies and spatial relationships between components within complexes at several resolutions (from macro scale to atomics scale resolution).

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). 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.