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PORTRAIT
December 2023 ESRFnews
T H E R O Y A L S O C I E T Y
The COVID-19 pandemic taught us
three things about science, according
to Stephen Cusack. First, that it is
amazingly powerful at shedding
light on complicated things when
under pressure, as shown by the
unprecedented rate of accumulation of
data on SARS-CoV-2 leading to rapid
vaccine development. Second, that
it needs to begin addressing animal,
human and environmental health in
a single conceptual framework – the
“one health” idea, which has been
gaining more traction in recent years.
Finally, says Cusack, science (and
hence society) benefits from maximal
openness and collaboration. “People
look back at the [early pandemic] as a
golden era for collaboration,” he adds.
In fact, Cusack’s career could be
more or less defined by collaboration,
in particular the one between the
Grenoble site of the European
Molecular Biology Laboratory (EMBL
Grenoble), which he led from 1989
until the middle of last year, and the
ESRF. Over those three decades,
hand in hand, the two institutions
have helped usher in one revolution
in structural biology after another. In
the beginning, there was the opening
of the ESRF itself, then the world’s
first third-generation synchrotron.
The intensity of its beams prompted
the EMBL and ESRF to invent new
methods of automation including
microdiffractometers and sample
changers automation that has
become even more necessary with the
yet more intense fourthgeneration
EBS Next came the cryoelectron
microscopy cryoEM resolution
revolution and the ability of cryoEM
facilities such as the EMBL
supported CM01 at the ESRF to
study very large and flexible molecular
complexes in extreme detail And
then most recently there has been the
sudden success of AlphaFold which
enables protein structure prediction
using artificial intelligence to interpret
the reams of experimental structural
data gathered by facilities such as
the ESRF and the EMBL over their
lifetimes.
“The EMBL–ESRF collaboration
has always been very strong, a lot of it
based on instrumentation developed
by EMBL Grenoble that is present
on all ESRF macromolecular-
crystallography beamlines and indeed
all over the world,” says Cusack.
“Now we’re looking at the new EBS
flagship beamline ID29 for serial
crystallography and the automation of
cryo-EM and X-ray microscopy, and
that’s almost certainly going to lead to
even more collaboration and benefit to
the user community.”
Starting out
Such developments are opening up
more possibilities in structural biology,
including performing structure
determination not in vitro but within
the cell, where all of life’s microscopic
ingredients are present at once. Cusack
could hardly have imagined this at
the beginning of his career. In the
early 1980s he had already begun
studying influenza virus via small-
angle neutron scattering at the Institut
Laue Langevin, the pioneer institute
on what is now the EPN campus. Since
then he has never stopped working on
the virus In the mid1980s he spent
a sabbatical at Harvard University
in Cambridge US learning the art
of Xray crystallography on the viral
spike protein He was thus ready to
take advantage of the ESRF when it
came online in 1994 I thought if
youre going to work on something
as a scientist it has to be something
challenging and worthwhile
Indeed it was Cusacks work
on the detailed mechanisms of the
replication machinery of influenza
T he ESRF and EMBL Grenoble have
collaborated throughout their history.
For Stephen Cusack, former head of
EMBL Grenoble, the long view is of
utmost importance.
Brothers in arms
STEPHEN CUSACK IN BRIEF
BORN: London (1952)
EDUCATION: BA in physics and theoretical physics,
University of Cambridge, UK (1973); PhD, theoretical
solid-state physics, Imperial College London, UK (1976).
CAREER: Postdoc, EMBL Grenoble (1977–1981);
Staff scientist, EMBL Grenoble (1981–1989); Head
of EMBL Grenoble (1989–2022). Fellow of the Royal
Society (2015–).
virus matured over three decades to the point where he
was able to give a recent talk with the decisive title How
influenza polymerase works In September dozens of
researchers worldwide including the 2009 Nobel Laureate
Venki Ramakrishnan and both EMBL and ESRF director
generals Edith Heard and Francesco Sette gathered
in Grenoble to celebrate Cusacks lifelong scientific
achievements It was a jovial affair says Cusack combining
hard science and humorous anecdotes but with a clear
message to young researchers If you have the opportunity
when you choose something to specialise in choose it with
longterm vision
Jon Cartwright
“Now we’re looking at
the automation of cryo-
EM and X-ray imaging,
and it’s almost certainly
going to lead to even more
collaboration”