Completed Cells, Biochemistry & Physiology Genetics & Molecular Biology

A Cluster for the Development of Dynamic 3D Nanoscopy

In plain English

AI plain-English summary

A new microscope will track individual molecules moving in three dimensions inside living cells, revealing how proteins, vesicles, and genetic material organise themselves in real time. This matters because current light microscopes blur objects smaller than 200 nanometres, while electron microscopes freeze dead samples. The gap between these two techniques has hidden the “big picture” of how cells process information—how transport vesicles navigate, how ribosomes assemble, and how chromatin folds. Watching these structures move in 2D is not enough; objects constantly drift out of the focal plane. This project builds a cluster of innovations to capture the vastly larger datasets needed for 3D imaging and to develop algorithms that classify and visualise the resulting patterns. If successful, this is fundamental science with no immediate practical application. It will give biologists a direct view of the dynamic machinery inside living cells, revealing organisational principles that are currently invisible. Similar fundamental advances in microscopy—such as the development of green fluorescent protein—later transformed drug discovery, diagnostics, and our understanding of disease mechanisms. This work could lay the groundwork for future medical insights, but its primary value is in answering a basic question: how do molecules coordinate inside a living cell?

View original technical description
Imagine if we could watch multiple molecules in living cells as they move and interact. This dream may seem years away, but it is now realistic to achieve real-time dynamic super-resolution imaging of multiple tagged proteins in three dimensions (3D) in cells and in tissues. This will allow biologists to discover large-scale patterns involving diverse structures including transport vesicles, ribosomes, and chromatin domains, all previously inaccessible because they lie in the gap between the resolution of electron (1- 2 nm) and light microscopy (200-300 nm). The “big picture” of cellular organization/information processing would emerge, with advances in understanding cell function in health and disease. While we can now do this in 2D, 3D imaging is needed to follow objects as they move out of the plane. Achieving 3D imaging is a major challenge and will require two orders of magnitude more information per cellular volume, and novel algorithms to classify, analyze, and visualize patterns from massive datasets. We propose specific innovations (Table 1) that, should allow us to achieve this over the next five years, given our team’s proven track record of success.

View the original record at the funder ↗

Researchers

Daniel St Johnston (EPMC Awardee)James Rothman (EPMC Awardee)Martin BOOTH (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

Nanoscopy of Dynamics in the Living Cell.
Microfluidic devices for 3D super-resolution imaging of single molecules in live cells
Advanced multidimensional optics to investigate biological complexity at the single-molecule level in living, functional cells
Volumetric and time-sequenced live-cell imaging
An accessible framework to achieve multi-dimensional live-cell super-resolution high-content screening

Original classification

Collaborative Award in Science

Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.