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The EMBL Outstation Grenoble, France, is situated in one of
Europe's most beautiful locations, the heart of
the French Alps, with a view of snow-covered mountains
and the ski slopes. The Outstation, a laboratory
of about 90 people, shares a campus with the European
Synchrotron Radiation Facility [ESRF], which produces
some of the world's most intense X-ray beams, and
the Institut Laue Langevin [ILL], which provides
high-flux neutron beams. The Outstation collaborates
very closely with these facilities in building and
operating beamlines for macromolecular crystallography,
in developing the associated instrumentation and
techniques and in providing biochemical laboratory
facilities and expertise to help external visitors
making measurements.
Within this exciting context,
the Outstation has a very active in-house research
programme in the structural biology of cellular
processes, making use of a wide range of techniques
including molecular biology, biochemistry, electron
microscopy, light scattering, neutron scattering,
X-ray crystallography and computing. The availability
of such a range of techniques, combined with the
neighbouring large-scale facilities, is vital to
the success of ambitious projects in modern structural
molecular biology.
A strong tradition in studying
systems involving protein-nucleic acid complexes
and viruses has contributed to making the Outstation
a leader in international high-throughput structural
genomics projects. The structural work on aminoacyl-tRNA
synthetases is particularly well known. A number
of synthetases were first cloned at EMBL Grenoble
and various different synthetase structures have
been determined, including several in complex with
cognate tRNA. Studies of protein-RNA interactions
have been extended to the mammalian signal recognition
particle and other proteins involved in translational
regulation and RNA transport. The analysis of protein-DNA
interactions and mechanisms of transcriptional regulation
is another important topic here. Structural analysis
of eukaryotic transcription factor DNA complexes
like the first STAT/DNA complex is now moving towards
the analysis of larger complexes involved in transcriptional
regulation.
Another major focus is the study of
RNA viruses, such as influenza, rabies and Ebola,
with the aim of understanding how they replicate
and assemble. In parallel, studies of the structure
and function of proteins involved in viral and cellular
membrane fusion is actively pursued [e.g. HIV gp41
and proteins involved in vesicle transport]. Some
of the projects at the Outstation depend on close
interactions with colleagues at EMBL Heidelberg
and collaborations are underway on proteins involved
in nucleocytoplasmic transport, translational regulation
and RNA metabolism. A new development at the Outstation
is the introduction of automated, high-throughput
methods to make structure determination more efficient.
This is connected to the Outstation's involvement
in the EU-funded SPINE project [Structural Proteomics
in Europe] and to the establishment with the neighbouring
ESRF, ILL and French national Institut de Biologie
Structural [IBS] of a Partnership for Structural
Biology [PSB]. A new team has been established at
the Outstation who will implement robotic systems
for crystallisation, protein expression and the
development of selection methods for finding protein
fragments or mutants with improved solubility properties.
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