Streamlining structural biology: Developing a high-throughput cloud-based cryo-electron tomography platform

Introduction

Cryo-electron microscopy (cryoEM) has revolutionized biomolecular research. It enables structure determination of proteins and their complexes at near-atomic resolution, informing on their mechanism of action and their role in disease. Importantly, it also assists the development of novel therapeutics.

Cryo-electron Tomography

Cryo-electron tomography (cryoET) is an emerging cryoEM modality, which has demonstrated the potential to determine protein structures at near-atomic resolution in their near-native environment.

Functionality of CryoET

Importantly, cryoET provides snapshots of macromolecules during their function, allowing us to capture different stages of biochemical reactions in the cell and inferring their temporal order.

Challenges in Data Analysis

However, cryoET relies on extensive computational data analysis. Current analysis pipelines require:

1. Extensive computational resources
2. Various software packages
3. A high degree of expertise to build and execute workflows for data analysis

Proposed Solution

Building on my previous research from the ERC Consolidator project BENDER, I propose to create a cloud-based workflow for standardized and automated high-throughput cryoET data analysis (CryoET-CryoCloud).

Benefits of CryoET-CryoCloud

This solution will not only reduce analysis time from months to days, but it will also make the method accessible to a broad community by:

• Eliminating the need for investment into expensive computational infrastructure
• Reducing maintenance through scarce qualified personnel

Impact on Research

My proposed workflow will both enable and democratize high-content data analysis of cellular tomograms, thus dramatically increasing our knowledge of the molecular machinery inside the cell.

Collaboration

To perform this work and reach the market rapidly, I will conduct CryoET-CryoCloud in very close collaboration with a team from the startup company CryoCloud, which emerged from my research group.