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December 2025 ESRFnews

FUTURE OF THE EBS

CONNECTOMICS

Wiring diagrams of the brain give us a mechanistic

understanding of how neurons generate brain

function and behaviour – and maybe even why brain

computation is dif ferent from artif icial intelligence. Most

of this so far has involved electron microscopes, and

making volumes from tens of thousands of individual

sections. Despite its achievements, this is time-

consuming, expensive and doesn’t scale well. 

Following some promising initial results from the

ESRF’s ID16A beamline, a new beamline, ID18, is

being designed. This will enable faster results at higher

resolution – with the goal of obtaining a complete

connectome of an entire mammalian brain. Andreas

Schaefer (right) recently received a £3.8m (€4.3m)

Wellcome Discovery Award to chart the brain circuitry

behind the sense of smell in mice using the beamlines.

“Currently, with electron

microscopy, a wiring

diagram of a cubic

millimetre of brain takes

years and millions of

dollars. In five years, at the

ESRF, I expect that it will

be a routine beamtime.”

Andreas Schaefer Francis Crick

Institute, UK

THE HUMAN ORGAN ATLAS

J. M A N U E L M A R T Í N G A R C Í A

SERIAL MACROMOLECULAR CRYSTALLOGRAPHY

Traditional crystallography captures proteins frozen

in time, but serial macromolecular crystallography

(serial MX) reveals their dynamics by stitching together

data from thousands of tiny crystals. Unlike earlier

methods that demanded large crystals and cryogenic

cooling serial MX works at room temperature and

resists radiation damage At the f lagship ID29 beamline

ultrafast Xray pulses are allowing researchers to time

resolve a molecules conformational changes after a

reaction is activated for example by light a change in pH

or contact with a separate compound there are various

sample delivery methods including highviscosity

extrusion f ixed targets and tape drives This synchrotron

molecular movie approach rivals that provided by

Xray lasers and gives a straightforward realtime

window into lifes fundamental machinery

“In five years, we should

be able to follow the

structural dynamics that

underpin catalysis and

drug resistance in real

time That would open

up new more precise

avenues for

understanding and

targeting disease

José Manuel Martín García Blas

Cabrera Institute of Physical

Chemistry Spain

F R A N C I S C R I C K I N S T I T U T E

A lung injured by COVID-19 was one of the f irst images to

derive from the EBS. With everything visible in 3D, from

the major airways down to the f inest micro-vasculature,

the image showed what was possible with newly

developed hierarchical phase-contrast tomography

(HiP-CT). Since then, the Human Organ Atlas has begun

in earnest at the f lagship BM18 beamline, facilitated by

a dedicated hub access mode. The project unites over

50 research groups, and is building an open database of

human organ imagery with unprecedented internal detail.

So far, it has reshaped our understanding of cardiac

conduction disorders, and has even been integrated into

pilot cancer diagnostics. Recent developments have

allowed scans of an entire human spine and knee in hard

and soft tissue, paving the way for full-body studies of

joint problems or the spreading of cancer.

P. L E E

“In the next few years,

I hope that we’ll be

imaging an entire

human body. That will

allow us to see for the

first time how our

organs are connected,

and how they work as a

complete system.”

Peter Lee, University College

London, UK