Imaging Ultrafast Single Particle Macromolecular Dynamics with X-ray Lasers

This project aims to develop ultrafast single-protein imaging using XFEL technology to enhance understanding of macromolecular dynamics and structural changes in biological processes.

Subsidie
€ 2.000.000
2024

Projectdetails

Introduction

Conformational dynamics are crucial for the functioning of most macromolecules, and a deeper understanding of these motions holds great promise for future discoveries in biology. However, it is difficult to probe the structure of macromolecules away from their most stable conformations, and time-resolved studies remain limited by the available techniques.

Advances in XFEL Technology

Today, a new generation of XFELs is growing. The extremely short pulse duration, high pulse intensity, and repetition rate of these lasers offer new research opportunities in physics, chemistry, and biology.

Since the first XFELs were proposed, the idea of obtaining images of individual proteins frozen in time has fascinated and inspired many, and we have been at the forefront of this quest. The combination of advances in XFEL technology with ESI has brought the dream of imaging hydrated single proteins by X-ray diffraction within reach.

Current Limitations

Currently, time-resolved studies in solution in the sub-ms range are conducted through solution X-ray scattering or spectroscopic methods, but they can only provide limited structural information. XFELs provide a way to dramatically improve our understanding of these time-scales.

Proposal Overview

This proposal aims to develop the science and technology to make ultrafast single-protein imaging a reality through a three-step approach:

  1. Develop diagnostics suitable for nanosized samples.
  2. Enable single protein X-ray diffraction imaging through new sample delivery instrumentation.
  3. Perform time-resolved single protein imaging experiments using the unexplored tender X-ray energy range.

Future Implications

Ultrafast imaging of macromolecules will reveal new horizons. As a single-molecule method with high time-resolution, it enables imaging the structural changes associated with fundamental processes such as:

  • Enzyme catalysis
  • Allosteric signal transduction
  • Protein folding

It also opens a way to record molecular movies and map the conformational landscape of isolated macromolecules for the first time.

Financiële details & Tijdlijn

Financiële details

Subsidiebedrag€ 2.000.000
Totale projectbegroting€ 2.000.000

Tijdlijn

Startdatum1-1-2024
Einddatum31-12-2028
Subsidiejaar2024

Partners & Locaties

Projectpartners

  • UPPSALA UNIVERSITETpenvoerder

Land(en)

Sweden

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