Get documents about "The influenza virus endonuclease
Document Sample
PSB et al.
P a r t n e r s h i p f o r S t r u c t u r a l B i o l o g y N e w s l e t t e r
N°5
With a flu pandemic
becoming more and
more likely in the near
future, UVHCI scientists
have made advances
towards understanding
the replication
mechanisms of the virus
June 2009
The influenza
virus endonuclease
Above: The structure shows an acidic active site
with two bound manganese ions that shows
structural similarity to bacterial endonucleases.
Every winter we suffer influenza virus oligonucleotide as a primer; ie. it
epidemics, which lead to between attaches its own mRNA to this bit of
250,000 and 1 million deaths per year capped cellular mRNA.
worldwide. Sometimes, however, a A few months ago the influenza virus
CONTENTS
bird virus infects a human being, and polymerase collaboration (the groups Scientific highlights:
if this virus can then be transmitted of Stephen Cusack, Darren Hart and • The influenza virus endonuclease . .1
from person to person, it can mutate Rob Ruigrok) determined the struc- • Probing deeply into protein
to adapt to humans. With no previ- ture of the part of the polymerase that structure and dynamics . . . . . . . . . . .2
ous immunity in the population, such binds the cellular cap (Guilligay et al., • Structural and mutational studies of
a virus can cause a giant worldwide drUvrA2 provide insight into DNA
2008, Nature Struct. Mol. Biol. 15, 500- binding and damage recognition . . .3
epidemic, called a pandemic, with up
• Ion-Channel-Coupled Receptors: A new
to 25-50% of the entire population
type of bio-inspired nanosensors . . .4
infected. The most recent pandemics
occurred in 1957 and 1968, but the News from the Platforms:
Drugs developed against
best known was the Spanish flu pan- • Successful completion of the Millenium
the cap binding and Project "D11 Revised" . . . . . . . . . . . .5
demic in 1918 that may have killed
between 40 and 100 million people. endonuclease activities • The HTX Lab: New tools to follow up
your Crystallisation Experiments! . .6
Like all viruses, influenza virus can may protect the lives of
Training:
make its own messenger RNAs but elderly people and those • 77 Dutch High School students visit the
not its own proteins because viruses with heart and respiratory PSB . . . . . . . . . . . . . . . . . . . . . . . . . . .2
do not have ribosomes. Therefore, the • Macromolecular crystallography
illness during our regular tutorial . . . . . . . . . . . . . . . . . . . . . . . .4
virus has to make mRNA that looks
like cellular mRNAs otherwise the annual epidemics • Surface plasmon resonance (SPR)
training at CIBB . . . . . . . . . . . . . . . .5
ribosomes will not be able to recog-
• PSB Course on Biological Small Angle
nise it. Cellular mRNAs all begin with Scattering with X-rays and
the same ‘cap’ structure, and they all 506). These groups have now also Neutrons . . . . . . . . . . . . . . . . . . . . . . .6
finish with a poly-A sequence. The determined the structure of the part
Announcements . . . . . . . . . . . . . . . . . . .3
molecule responsible for making the of the polymerase that cleaves the cel-
influenza mRNA, the viral poly- lular mRNA. They could isolate the Profile: Laurence Serre . . . . . . . . . . . . .7
merase, can make the poly-A domain that performs this activity and Students’ corner . . . . . . . . . . . . . . . . . .7
sequence but not the cap structure. In they were able to show that, in the
The PSB students Day 2009 . . . . . . . . .7
order to fix a cap to its mRNA, the presence of manganese ions, it has the
polymerase binds to the cap of a cel- same biochemical activity as the intact Spotlight:
lular mRNA and then cleaves this viral polymerase. The • PSB: Mission accomplished . . . . . . . .8
RNA 10-13 nucleotides down its structure shows an acidic Newcomers . . . . . . . . . . . . . . . . . . . . . . .8
sequence and then uses this capped active site with two (see page 2)
1
bound manganese ions that shows of the ESRF. binding and endonuclease activi- Thibaut Crepin (EMBL),
structural similarity to bacterial Apart from the pure scientific inter- ties may come to be very useful Alexandre Dias (UVHCI),
endonucleases (see figure). These est of these findings they also per- when a new pandemic hits and may Stephen Cusack (EMBL), Rob
results were obtained with the help mit high throughput drug also protect the lives of elderly peo- Ruigrok (UVHCI)
of the quality control and the High screening with small, well defined ple and those with heart and respi-
Throughput Crystallization plat- and well- behaved protein domains. ratory illness during our regular Dias, A. et al.(2009). Nature 458,
forms of the PSB and the beamlines Drugs developed against the cap annual epidemics. 914-918
Probing deeply into protein structure and dynamics
The adaptation of living organisms the S. cerevisae IF6. The protocols
to extreme environmental condi- for the production of deuterated
tions is a challenging area. Near proteins were developed at the
deep sea hydrothermal chimneys, ILL–EMBL Deuteration
temperatures can vary from 4°C to Laboratory of the PSB. Quasi-elas-
100°C within very small distances, tic neutron scattering data were col-
while pressure usually reaches lected at the IN16 and IN5
200atm. In this environment, chem- beamlines at the ILL.
ical equilibria are altered; organ- The results showed very similar
isms adapt through global dynamic properties for the two
optimization of structures and Screwfit describes backbone
homologous IF6; in particular, structure using quaternionbased
metabolic pathways. atomic fluctuations, seen at differ- superposition fits of peptide planes
in conjunction with Charles’
During his PhD in the Scientific ent length scales, became compa- theorem (“every rigid-body
Computing Group at the ILL – rable at in situ conditions. This displacement can be described by a
under the supervision of Mark supports the hypothesis that molec- screw motion”)
Johnson and in collaboration with ular evolution precedes maintain-
Gérald Kneller (Centre de ing ‘corresponding states’ of protein
Biophysique Moléculaire/ function at different environmen-
Synchrotron Soleil) – Paolo tal conditions and allowed, for the
Calligari studied the effects of ‘deep- first time, the extension of similar
sea’ pressure and temperatures on findings previously reported in
both structure and dynamics of an thermophiles to the domain of of dynamical adaptation in molec- of viral neuraminidases (surface
initiation factor, IF6, required for high-pressure/high-temperature ular evolution of proteins issued glycoproteins that allow the
ribosome biogenesis and function. environments. Molecular dynam- from organisms living in extreme influenza virus penetration and the
Combining neutron scattering and ics further allowed the evolution- conditions. egress of virions). The results iden-
molecular dynamics, molecular sig- ary role of the additional C-terminal Lately Paolo Calligari was also tified family specific structural
natures that make possible the fragment in S. cerevisae IF6 to be involved in the development of an effects that are relevant to the design
adaptation to extreme environ- elucidated: its presence is crucial open source program, Screwfit, to of inhibitors.
ments were identified. A compara- for the dynamical correspondence characterise protein secondary Susana Teixeira (ILL)
tive analysis was done on M. between the two homologues at structure in terms of screw motions P.A. Calligari et al. (2009), Bioph.
jannaschii IF6 – this 3 billion-year- their respective natural tempera- (see http://dirac.cnrs-orleans.fr/ Chem. 141, 117-123
old archaeon lives in warm, deep ture and pressure. These findings ScrewFit). Screwfit was applied to
sea (2600m under sea-level) – and showed evidence of a relevant role a comparative analysis of inhibition ■
Training at the PSB
77 Dutch High School students visit the PSB!
Last March the PSB received a visit introduced them to bending mag- gle particle reconstruction. Finally This visit was challenging, as most
from 77 high school students (yes, nets and undulators. Wim Bras took they visited EMBL and the UVHCI, of the installations could not easily
77!) from the Netherlands. Their them to the experimental hall and where they were enthralled by pre- accommodate such an amount of
first stop was the ILL where they explained some of the experiments sentations from Daniel Panne, who visitors, but it was very profession-
were welcomed in Dutch by running on BM26. explained how cells defend them- ally organised by Ingeborg Tegroen.
Ingebor Tegroen (ILL), who intro- At the IBS they received a general selves against viruses, and Rob In turn, the scientists appreciated
duced them to the fascinating world introduction to structural biology Ruigrok, who insisted that ‘viruses the opportunity to talk to the young
of neutrons before they were given by Anne Volbeda (LCCP) and are beautiful!’. They also appreci- people and motivate them towards
a tour of the facilities and the neu- colleagues from the NMR team. ated the presentations by Andrew science. They certainly responded
tron guides with Susana Teixeira They were also able to appreciate Mcarthy on structural biology and with a lot of interest.
and Antonio Perillo-Marcone. The adenovirus particles under the elec- Ramesh Pillai, who talked about José A. Márquez (EMBL), Susana
students then proceeded to the tron microscope, where Winnie snRNAs, the new weapons in the Teixeira (ILL), Anne Volbeda
ESRF where Peter van der Linden Ling introduced the concepts of sin- arsenal against disease. (IBS)
2
Scientific highlights
Structural and mutational studies of Deinococcus radiodurans UvrA2 provide
insight into DNA binding and damage recognition
Nucleotide excision repair (NER) of conservation suggests that the
is the primary pathway for repair molecular mechanisms involved in
of the structurally diverse lesions substrate recognition are most likely
caused by ultra-violet light and similar to those used by Class I
involves the recognition and UvrAs.
removal of damaged DNA by a In our study, we show that drUvrA2
dual-incision event. In prokaryotes, shares many of the biochemical
the Uvr proteins carry out the exci- (ATPase activity, nucleotide-depen-
sion and have been the focus of dent dimerisation, preferential
many studies for over 20 years. The binding to damaged DNA) and
proteins UvrA and UvrB are structural features observed for
responsible for the ATP-dependent UvrAs. We have solved and refined
recognition of DNA damage whilst the structure of ADP-bound
UvrC is required for the subsequent drUvrA2 in two crystal forms to
incision events. Despite extensive resolutions of 2.3Å (C2; 3 mol/asu)
biochemical and genetic studies, it and 3.0Å (C222; 2 mol/asu) respec-
is still not well understood how tively, providing us with a view of
NER is capable of recognising such five distinct monomeric and three
a wide variety of lesions, but as dimeric conformational states.
structural information on the
UvrABC proteins is becoming
available and through in depth bio-
Our analysis contributes
chemical analysis of the repair pro-
cess, a picture is starting to emerge. to an extended model Structure of D. radiodurans UvrA2. (A) Surface and ribbon representations of dimeric and
monomeric drUvrA2. The domains are coloured as follows: NBD1 (blue), NBD2 (cyan),
UvrA is responsible for initial DNA for how UvrAs might Insertion Domain (red) and Zinc-finger (raspberry). Zinc ions are illustrated as yellow spheres.
damage recognition and subse- interact with DNA, which (B) Models of dsDNA binding to symmetrical dimers assembled from the three different
molecules of drUvrA2 refined in C2 space group
quently acts as a molecular match- has implications for a
maker by efficiently promoting the
fuller understanding of
stable assembly of UvrB onto dam-
aged DNA sites. A more compre- the mechanisms This work was complemented by a tion of a Class II UvrA and also
hensive description of the molecular involved in the initial mutational study of drUvrA2 that contributes to an extended model
mechanisms of UvrA’s action would steps of NER showed that two regions of UvrAs for how UvrAs might interact with
therefore constitute an important are essential for DNA binding: a DNA (see figure), which has impli-
contribution to our understanding positively charged groove formed cations for a fuller understanding
of the initial steps in bacterial NER. drUvrA2 assembles as a head-to-
on the concave side of the core ABC of the mechanisms involved in the
In this work, we have undertaken a head dimer in which each
domains and the newly identified initial steps of NER.
structural and biochemical study of monomer consists of two tandemly
Insertion Domains. Taken together
a UvrA protein (drUvrA2) from the arranged ATPase binding cassettes Joanna Timmins (ESRF)
our structural, biochemical and
radiation-resistant bacterium (see figure). As expected from pri-
mutational analysis of drUvrA2 Timmins, J. et al. (2009).
Deinococcus radiodurans. Unlike E. mary sequence analysis, our struc-
provides the first detailed descrip- Structure, 17, 547–558
coli, D. radiodurans’ genome ture of drUvrA2 reveals that the
encodes two UvrA proteins, UvrB-interacting domain is miss-
drUvrA1 and drUvrA2. drUvrA1 ing along with its associated Zn-
represents the full-length UvrA pro- binding site (two CXXC motifs). As
tein, which is present in all bacte- a result, drUvrA2 possesses only Announcements
ria and has recently been classified two of the three Zn-binding sites
as a Class I UvrA. Recently, the first found in the classical Class I UvrAs. The next Neutrons in Biology meet- The EMBO/MAX-INF2 Practical
three-dimensional structure of such As in the case of bstUvrA, a large ing (NIB2009) will take place in Course on Structure Determination
a Class I UvrA from Bacillus Insertion Domain was accommo- Lund University, Sweden, on 22-24 in Macromolecular Crystallography,
stearothermophilus (bstUvrA) was dated in the amino-terminal organised by ESRF and EMBL, will
June. This meeting is a unique
reported. drUvrA2, a Class II UvrA, nucleotide binding domain (NBD- be held from 15-19 June 2009. This
opportunity for students and scien-
displays a high sequence identity I) of drUvrA2, while a more classi- practical course addresses young
cal zinc-finger is inserted into the tists to find out what neutron scat-
with drUvrA1, E. coli UvrA and scientists who intend to apply sin-
carboxy-terminal NBD-II. tering techniques can do for
bstUvrA, but is missing the UvrB gle and multiple wavelength
structural biology. anomalous scattering (SAD & MAD)
binding domain recently identified Our studies have also shown that
in bstUvrA. Although the exact drUvrA2 alone can recognise and Registration is now open online at methods in macromolecular struc-
roles and substrates of Class II bind preferentially to damaged www.ill.eu/nib2009. ture determination.
UvrAs remain elusive, the high level bases within DNA oligonucleotides.
3
Scientific highlights cont.
Ion-Channel-Coupled Receptors: A new type of bio-inspired nanosensors
Michel Vivaudou’s group Ion-Channel-Coupled Receptors or were designed and successfully directly generate electrical signals
ICCRs as illustrated in Figure 1A. tested. New ones are actively pur- is a key feature for integration
has explored the
The key point is the mechanical sued. They could be used for the within microelectronic systems.
possibility of coupling connection between the receptors development of new drug screen- Christophe Moreau, Lydia Caro,
two proteins to construct and the channel: A receptor moves ing assays, for in vitro diagnostics Jean Revilloud and Michel
biosensors to be used in when it binds a molecule and a or detection of toxic agents. These Vivaudou (IBS)
channel moves when it opens and biosensors could detect and signal
microelectronics devices closes. By bringing them close Moreau C.J. et al. (2008). Nature
the presence of exceedingly small
enough together, we hoped to syn- Nanotech. 3:620-625
quantities of molecules (hormones,
Originally the work was conducted chronize receptor’s motion with the neurotransmitters). Their ability to ■
within the European project opening/closing of the channel.
Receptronics (www.receptronics.
The structures and the dynamics of
org). The goal was to combine
receptors and channels are, in large
seemingly irreconcilable properties:
part, unknown and they can only
a miniature size in the nanometric
be predicted with very little confi-
scale, the ability to detect and iden-
dence (Figure 1B). Rational design
tify tiny amounts of molecules, and
is therefore not possible and one
the capacity to produce an electri-
must rely on a time-consuming
cal signal readily detectable by elec-
trial-and-error approach. Our
tronic equipment.
approach consisted in using pro-
To reach this goal, we took advan- tein engineering and molecular
tage of the natural devices used biology techniques to create hybrid
throughout the body to translate proteins associating receptors and
biochemical signals into electrical channels in various arbitrary ways,
ones: receptors and channels. As in expressing these constructs in
cells are delimited by an imperme- Xenopus oocytes, and in testing the
ant lipid membrane, the flow of functional coupling between recep-
‘information’ is handled by spe- tor and channel with electrophysi-
cialised membrane proteins: recep- ological techniques. After much
tors identify chemical signals effort, we eventually defined the
arising from other cells or the envi- optimal way to build an Ion-
ronment while ion channels con- Channel-Coupled Receptor.
trol the ion flux to generate an Basically, the receptor C-ter and
electrical signal. channel N-ter extremities were
We thought that, by combining fused together and physical cou- Figure 1: A. The principle of ICCRs (Ion-Channel-Coupled Receptors). When the receptor
these two elementary building pling was achieved by deleting parts recognises a molecule X, it undergoes a structural change that is transmitted to the channel. The
of these extremities thus bringing degree of opening of the channel is consequently modified and the ion flux through the channel
blocks into a single protein, one is altered. This ion flux is easily detectable as an electrical current. In essence, this artificial couple
could construct novel sensors with the protein components closer. acts as a chemical-gated transistor with a very large gain (1 ligand-binding event = ~107 ions/s
through channel). B. Side view of a molecular model of an ICCR tetramer with front and back
the desired chemical signal recog- As proof-of-concept, biosensors for monomers removed. The channel (K+ channel Kir6.2) and receptor (G-protein coupled receptor
nition property. This is the basis of two major pharmacological targets M2) are fused in the circled region.
Training at the PSB
Macromolecular crystallography tutorial
Another highly successful tutorial lenge to find a level that took into symmetry and molecular replace- School at Grenoble University.
in macromolecular crystallogra- account the different scientific ment. They were accompanied by
I want to thank the sixteen partic-
phy took place last winter for an background of the participants. pencil and paper exercises. The
audience of PhD students, post- tutorial ended with MAD data col- ipants who came from the differ-
docs and staff from the PSB part- Subjects covered in the lectures ent PSB partner institutes and
lection on our test crystal system,
ner institutes. With 11 sessions of were space groups, symmetry and ferulic acid esterase, and practi- assisted throughout the tutorial,
lectures, exercises and hands-on twinning, reciprocal lattice, cals where the structure was deter- for their enthusiasm.
practicals, the aim was to refresh diffraction physics and Fourier mined using MAD and molecular This tutorial will be offered again
or deepen the audience’s under- transform, oscillation method, replacement using current soft-
at the beginning of 2010.
standing of the basics of protein Patterson analysis, experimental ware. Six PhD students validated
crystallography, despite the chal- phasing, non-crystallographic the module for the Doctoral Wim Burmeister (UVHCI)
4
News from the platforms
Successful completion of the
Millennium Project “D11 Revised”
The renewed D11
instrument: the 40 meter-
long evacuated detector tank
D11 is the archetype of a long pin- formance in these particular fields. momentum
hole-geometry instrument, Plans for the future include the transfer Q
designed for small angle neutron option of installing a multi-beam (due to the
scattering (SANS) studies of large USANS (ultra-small angle). larger size of
scale structures in chemistry, biol- the new
The instrument has now been com-
ogy, materials science and solid state detector) only
pletely redesigned and rebuilt to
physics. It has been in operation at 3 sample-to-
include a new detector on a new
ILL since 1972 and its unique broad detector dis-
trolley inside a larger and longer
range of momentum transfer, low tances are
aluminum vacuum tank, as well as necessary for
background and high flux make it
the world’s leading neutron instru- a complete replacement of 39 m of measuring
ment of its kind. glass neutron guides on the colli- the complete
mation side. scattering
Although D11 has undergone a
continuing renewal over the past The instrument performs with the curve from
new guides even better than esti- Qmin to
three decades, a major refurbish-
mated. Compared to 2005 a gain in Qmax, com-
ment has been performed over
neutron flux of more than 50 % has pared to 4
recent years. The overall strategy
been measured for long (≤ 34 m) to distances
for the 3 SANS instruments at ILL
intermediate collimation distances. before. At the
(the existing D11 and D22 com-
At short collimation distances (≤ same time,
bined with the upcoming D33 pro-
5.5 m) the flux increases very the flux on
ject) ensures a broad versatility of
strongly due to the performance of the detector is
SANS capability while emphasising in user operation – definitely good
the focusing guide section. The significantly increased.
the particular strengths of each news for the PSB users interested
individual instrument. In this maximum flux for wavelength λ = This unique 80 m SANS instrument in doing SANS studies.
respect D11, which has always been 6Å (FWHM Δλ/λ = 9%) is now ≈ is now reborn and the upcoming
1 108 n cm-2 s-1 (compared to ≈ 3 user programme in 2009 will cre- Peter Lindner & Ralf Schweins
widely used for soft matter and bio-
107 n cm-2 s-1 in 2005). At the new ate a new benchmark for SANS. (ILL)
logical research, is now being
improved to give even higher per- D11, with its extended range of Since 26 March D11 has been back www.ill.eu/d11
Training at the PSB
Surface plasmon resonance (SPR) training at CIBB
Nearly all cellular processes depend Label-free biosensor-based surface quantifying their kinetic parame- course a week later.
on protein-protein interactions. plasmon resonance (SPR) systems ters, as these instruments allow A total of 20 participants (11
Measuring these is key to gaining are now commonly used in the real-time measurements.
EMBL, 6 ESRF, 3 ILL) attended.
insights into the biochemical study of diverse biomolecular The PSB partners acquired a sec- The course aimed to provide a the-
mechanisms that underlie disease interactions, and have become a ond Biacore X SPR instrument in oretical understanding of the fun-
and for developing new drugs. widely accepted technology for April 2008, extending damentals of the SPR biosensor
the capacity of the IBS’ technology, experimental design
Biacore platform with and preparation of the sensor chip.
the key advantage of Moreover, it included a practical
being located in the session in the laboratory on mea-
CIBB building. To pro- surement of a protein-protein
mote use of the interaction.
method, we organised
Since the course, a number of sci-
a training course for
entists have registered as users of
PhD students and
this instrument and have already
postdocs on 20
February – and an generated successful data.
overwhelming demand Stéphane Boivin (EMBL) &
led to a repeat of the Nicole Thielens (IBS)
Left: the new Biacore X at the CIBB
5
News from the platforms cont.
The HTX Lab: New tools to follow up your Crystallisation Experiments!
The high throughput crystallisation Management System) that allows on clear and precipitated drops particular crystallisation experi-
platform at the PSB, the HTX Lab, automatic data tracking, reducing (provided a minimum number of ment and the data matrix in the
has been in operation now for more manual input, integrates systems drops have been scored) which can SPINE sample loops. Once all the
than 5 years and is the result of a from different suppliers and offers help you decide, for example, samples for a particular syn-
collaboration between EMBL and a number of basic and advanced whether the concentration at which chrotron session have been
the IBS. It offers automated nano- functionalities to the users, like the sample was assayed was appro- mounted, the information can be
volume crystallisation screening at drop viewing and annotation, nav- priate. It also offers the possibility transferred from CRIMS to ISPyB,
20ºC and 4ºC in a variety of exper- igation through project and sam- to make annotations on individual associated to a particular MX num-
imental setups. Results, along with ples, etc. experiments, so it can be used as an ber. Once the samples are moved
all the experimental details, are Recently we have added important electronic lab book. to the synchrotron, the automatic
available in real-time through our functionalities to the system. The The second recently developed tool sample exchanger simply scans the
own dedicated, secure web inter- first is the summary page. This util- allows a direct connection between pin barcodes, and the names of the
face. ity collects the most interesting CRIMS and ISPyB, the information samples as they appear in the
Since the start of operations the experiments from a screening in a management system for data col- CRIMS interface will automatically
HTX lab has helped more than 350 single page along with all the exper- lection used at the ESRF and the appear in the MX Cube interface
scientists to find crystallisation con- imental information. This not only automatic sample changer. A web for data collection. Once the exper-
ditions and has performed well over permits visualising the results application, specifically designed to iments are performed, the summary
2 million individual crystallisation rapidly and conveniently, but also be used during the process of page in the CRIMS interface will
experiments, which makes it one of can help indentify crystallisation mounting and freezing crystals and show information on the x-ray
the largest platforms of its kind in trends in your sample. The sum- accessible from the summary page, diffraction experiments indicating
Europe. Since April this year mary page also provides statistics establishes a direct link between a the number of frames collected and
European scientists ouside the PSB providing links to the correspond-
have had access to the HTX lab ing ISPyB samples. We believe this
crystallisation screening services new interface will be useful to
through the EC funded infrastruc- streamline the follow up of crys-
ture project PCUBE (see tallisation experiments and can be
https://htxlab.embl.fr for details). extremely valuable when large
numbers of samples are tested at
An important part of our effort has
the synchrotron.
been dedicated to the development
of a data management system and The versatility and the number of
user interfaces adapted to the crys- functionalities available in CRIMS
tallisation process and the size of has made it jump the frontiers of
the facility. Initially data handling the PSB. During the past year, ver-
at the lab relied mostly on software sions of CRIMS have been installed
accompanying the robotic compo- in three other crystallisation labs,
nents. However, as throughput including EMBL Heidelberg and
increased, this situation was not Hamburg and the Weizmann
sustainable as it was difficult to Institute in Rehovot, Israel – a good
adapt the software to our process example of how the work at the
or to integrate systems from differ- HTX lab, as well as the feedback
ent suppliers. and experience accumulated from
users of the platform at the PSB, is
Over the last four years we have
benefiting other scientists in
developed a central data manage-
Europe!
ment system, CRIMS The summary page of CRIMS showing the new functionalities. From top left: mount information;
(Crystallisation Information ISPyB link; X-ray information. José A. Márquez (EMBL)
Training at the PSB
PSB Course on Biological Small Angle Scattering with X-rays and Neutrons
The first PSB course for Biological by Joe Zaccai (ILL) and Frank small angle scattering beam lines organisers would particularly like
Small Angle Scattering with X-rays Gabel (IBS), practicals at D22 (Phil of both the ILL and the ESRF in to thank Daniel Franke and
and Neutrons took place on 14-17 Callow, ILL) and ID14-3 (Adam the near future! Maxim Petoukhov from EMBL
April, demonstrating what sort of Round, EMBL) and data analysis Given the success of this course it Hamburg (Svergun Group) for
information the technique can tutorials, the participants appeared will be repeated at regular inter-
their contributions.
provide and how to get the most enthusiastic throughout. We vals, with a more advanced course
out of experiments. With lectures expect to see many of them at the planned for later in the year. The Phil Callow (ILL)
6
Profile
Collaborations and major projects
with several partners can only work Laurence Serre, – from all four partners.”
Laurence has already set up the
effectively if communication is good,
and that’s why the Partnership for PSB Scientific Animator PSB’s first Student Committee (see
Structural Biology (PSB) has enlisted below), and she also organised an
the help of Laurence Serre. event in December for the people
running the PSB platforms to pre-
With the impressive title of
sent their activities. She plans to
Scientific Coordinator/Animator,
Laurence, who is a protein crystal- help the group leaders with grant
lographer ‘on loan’ from the CNRS, applications, as well. “There are 300
will coordinate the science, events people in the PSB – scientists, tech-
and training for the PSB partners nicians and students. I hope that
– EMBL Grenoble, the European building on and improving the net-
Synchrotron Radiation Facility, the working within the partnership will
Institut Laue Langevin and the mean that people outside will asso-
Institut de Biologie Structurale. ciate the PSB with excellence in sci-
“The PSB is made up of interna- ence and education. I want people
tional and French institutions across town or at the university to
that are all very different,” say: ‘Oh, there’s something happen-
explains Laurence, who studied ing at the PSB – a seminar or other
in Marseilles and Paris before
event – so for sure it’ll be good!’
doing a postdoc in Canada.
“Although they’re close together “For now, though, it’s more impor-
physically, it’s sometimes very dif- tant to improve communication
ficult to get people connecting have the most effective exchanges much as possible. In an environ- on the inside. I’m going to survey
with each other. Even here, in the with those on different floors!” ment like this, they can meet peo- the students and see what they
the Carl-Ivar Brändén Building ple who will be very useful to them want. I hope that the ones who are
(the PSB ‘headquarters’, which Laurence has lots of ideas about and their careers in the future. In involved already will spread the
houses 100 people affiliated to how to make this happen. “I think January we had the first PSB stu- word, and that little by little we can
the partners, laboratory space the best place to start is with the dent’s day (see below), where we
build a great network.”
and several technical platforms) young scientists,” she says. “I try had 50 students – more than half
it’s not always obvious how to to encourage them to network as our total number of PhD students Vienna Leigh (EMBL)
Students’ Corner The PSB Students
Day 2009
Partnership for Structural Biology Student Committee The first PSB student day took place
on 30 January at the ILL, giving
With so much exciting scientific Following the success of the PSB of all new PSB students in PhD students from EMBL, ESRF,
activity happening at the PSB in students day held at the end of October/November are underway, IBS, ILL and UVHCI a chance to
Grenoble, a Student Committee January this year, the PSB Student as well as a cocktail party to be present their thesis work and them-
has been formed to represent us Committee is planning several held after the PSB SAB visit on 18 selves in an informal and relaxed
– the students of the PSB – and to other events in 2009 to bring June. So there’s lots to look for- way and encouraging people from
organise events where students together both students and lead- the different institutes to interact.
ward to!
and leading senior scientists can ing scientists in an informal envi- Selected students presented their
come together to share and dis- ronment. Plans for the welcoming Bridgette Connell (IBS) work, and there was a short clip pre-
cuss ideas and thoughts and to sentation and a poster session.
Prizes for the best clip and poster
create new scientific networks.
were won by Bridgette Connell and
The PSB committee is composed Ambroise Desfosses.
of nine members, each of which
The day was a great success mainly
are currently enrolled in a PhD
due to the enthusiasm of the stu-
programme at either the EMBL, dents but also thanks to the partic-
UVHCI, IBS, ESRF or ILL. The ipation of PSB group leaders, staff
members are all at different stages scientists and postdocs. The PSB
of their PhDs, so there will be a student committee would like to
chance for new students to join thank all the people who helped to
the group each year. The current From left to right: Eva Kowalinski (EMBL), Ivan Ivanov (ILL/UVHCI), Bridgette Connell (IBS),
Isma Hachi (IBS), Alexandre Dias (UVHCI), Sofia Caria (ESRF), Marion Sevajol (IBS), Thierry make it happen, especially the stu-
members are pictured right. Izore (IBS) and Shona Gillespie (ILL) dents for their participation.
Alexandre Dias (UVHCI)
7
Spotlight
The Partnership for Structural Biology: mission accomplished?
The PSB was established European visibility. So the answer
is: Yes, definitely, the mission has
in November 2002 by
been accomplished!
EMBL, ESRF, ILL and IBS.
So what next for the future of the
It was born during the partnership? Of course, new tech-
heyday of structural nical approaches can be developed
genomics with its such as the biophysics or imaging
emphasis on the platforms that will certainly bring
added value to the site. Increasing
development of new internal scientific collaborations is
tools for high throughput still a big issue for the PSB and can
studies. be judged by the increasing num-
ber of publications involving more
Now structural genomics has given
than one partner. In this context,
way to ‘integrated structural biol-
the involvement of the students in
ogy’ and ‘structural cell biology’
PSB life and the likely move of the
with the recognition that biologi-
IBS onto the international site are
cal systems have to be studied in
very positive steps.
an integrated way, using methods
that span resolutions from atomic Opening the PSB and its platforms
to cellular levels, and employing to outside users and industry is also
diverse techniques for sample important for the future. This will
preparation and in vitro and in vivo from a collaboration between the Access to the broad range of PSB require additional funds, people and
biophysical and structural charac- ESRF, ILL and EMBL. techniques has significantly lab space. The PSB is already look-
terisation. To address this challenge enhanced in-house structural biol- ing to expand European academic
The unique methodologies avail-
the PSB has implemented a num- ogy research. The technical plat- access via the new EU FP7 PCUBE
able on the PSB platforms have
ber of technical platforms avail- forms and the complementary transnational access project, and
made very original and outstand-
able to PSB, and in some cases expertise provided by the PSB have IBS2 could be a chance to house
ing studies possible. By combin-
external, scientists. Indeed the brought added value to the pro- new innovative start-up enterprises.
ing crystallography and micro-
technical platforms are still the jects developed; for example, the Building up interactions with other
spectroscopy on crystals at the
core of the partnership without influenza polymerase study (see biology centres and industry at dif-
Cryobench and X-ray Data
which challenging scientific pro- page 1) or the structural genomics ferent levels (regional, national and
Collection platforms, IBS/ESRF
jects cannot be done. project deciphering the molecular European) is also a major issue for
teams have achieved innovative
Twelve technical platforms are now bases of the extreme radiotoler- the PSB, in particular regarding the
work on fluorescent proteins, offer-
co-operated by the PSB partners, ing exciting perspectives for the ance of Deinococcus radiodurans position of Grenoble within the
ranging from protein expression development of two-colour super- bacteria, both resulting in publi- INSTRUCT (a European infrastruc-
to biophysical methods based on resolution optical imaging. Using cations in high-impact journals. ture for Integrated Structural
large facilities. They represent a the library-scale random construct The PSB has created a unique envi- Biology, www.instruct-fp7.eu) ini-
long-lasting collective investment screening technology, ESPRIT, ronment for performing state-of- tiative.
for the research of each partner. UVHCI teams studying influenza the-art, international class Laurence Serre (PSB), Stephen
Over the past two years, three new polymerase PB2 subunit tested structural biology with high Cusack (EMBL)
platforms have been implemented, nearly 60,000 separate con-
allowing micro-spectroscopy and structs to identify three sepa- The Partnership for Structural Biology
kinetic crystallography (Cryo- rate domains responsible for (PSB) is a collaboration between a
bench, IBS/ESRF), protein produc- nuclear transport, mRNA cap number of prestigious European and
tion in insect cells (Eukaryotic binding and host adaptation of French scientific laboratories in
avian viruses to humans; stan- Grenoble which has received support
expression facility, EMBL) and
from the EU FP6 programme. The
small angle scattering (SAS plat- dard methods of sequence PSB is unique in combining world
form) with both SAXS and SANS, alignments had failed to iden- leading user facilities for synchrotron
an innovative platform resulting tify those domains. X-ray and neutron scattering with
NMR, electron microscopy, molecular
biology and high throughput
techniques on a single site together
Newcomers with strong projects in a broad range
of structural biology, notably host-
pathogen interactions.
Daniele de Sanctis has joined the Hanna Wacklin has come all the
ESRF MX group as a beamline sci- way from Australia to join the team Contacts
entist on ID23-EH1 and ID29. He at FIGARO, the new time-of-flight Editors: Susana Teixeira (ILL), Dominique Housset (IBS), José A.
will work to extend the applicabil-
ity of the tunable beamlines, reflectometer instrument (see the Márquez (EMBL), Joanna Timmins (ESRF). Composition: Vienna
December 2008 PSB Newsletter) at Leigh (EMBL) and SoftOffice. Contact: cisbnewsletter@embl.fr
exploiting small anomalous signals
Links: www.psb-grenoble.eu
and radiation sensitive samples. the ILL.
8
Related docs
