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ISMB News
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This page contains recent ISMB News items. Previous ISMB news items are available here. |
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ISMB Graduate Symposium, 11-12 June 2013
May 2013
This annual event is designed to give PhD students at the ISMB the opportunity to present their work and is typically attended by over 100 PhD students and supervisors.
The 2013 ISMB Graduate Symposium will take place on Tuesday 11 and Wednesday 12 June in the JZ Young Lecture Theatre, Anatomy Building, UCL.
Professor Liz Shephard, Research Department of Structural and Molecluar Biology, will be the guest speaker.
Full programme details will be circulated among members of the ISMB soon.
[Posted: May 2013]
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UCL student wins Eisenthal Prize to work with Professor Steve Perkins
May 2013
Congratulations to Anna Miles, a second year Biochemistry student at UCL, who was this year's winner of the Biochemical Society Eisenthal Prize to carry out a summer studentship project with Prof Steve Perkins at UCL.
[Posted: May 2013] |
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Featured Publication
April 2013
Structural and Energetic Basis of Folded-Protein Transport by the FimD Usher
Geibel S., Procko E., Hultgren S.J., Baker D., Waksman G. Nature 496, 243–246, doi:10.1038/nature12007
Published this month in Nature, Prof Gabriel Waksman, his group member Dr Sebastian Geibel and their collaborators have revealed the structural and energetic process by which bacteria transport pili across their outer membrane. Pili are a key target for a new generation of antibiotics, as without them bacteria are unable to group together and to stick to human cells causing infection.
In the cystitis bacteria, pili enable bacteria to group together and then to attach to the wall of the bladder. The bladder cells then engulf the bacteria and this makes antibiotic treatment very difficult. Once inside the bladder cells the bacteria can lie dormant, making recurrent infections common. It is believed that a new generation of antibiotics could be developed to disrupt the process of pili biogenesis, making the condition easier to treat.
Previous research by the ISMB members uncovered how pili biogenesis is initiated by the protein FimD – an usher in the outer cell wall. FimD is responsible for recruiting subunits, assembling them into a pilus, and secreting the pilus as it is being formed. From this work, the team was able to develop a model for the way the usher carry out all these tasks. The latest research, funded by the Medical Research Council, provides experimental proofs for the model proposed before and shows how, once the subunits have been assembled, the new pilus is secreted from inside the FimD protein to the exterior, via a pore, across the outer bacterial membrane.
The team has now revealed that as the pilus is assembled, the first subunit (FimH) engages with the usher and undergoes structural changes. This creates the necessary energy for this subunit, which forms the tip of the pilus, to displace the plug which is normally found inside the pore, and to pass through the pore itself. As subsequent subunits of the pilus pass into the pore, other structural changes in FimH prevent the pilus retreating back through the pore.
The team has also revealed that within the usher’s pore there are specific binding sites for the tip and the subsequent subunits of the pilus. These binding sites are 180 degrees apart within the barrel of the pore (facing each other); so that the pilus is held in a central position as it emerges from the pore, facilitating its exit. Furthermore, it has n that as the pilus passes through the pore it follows a rotational and translational path, enabling subsequent subunits to continue being added within the usher as the tip emerges, while the pilus is still held in a central position.
"For the first time we have been able to see the structural and energy pathways via which the FimD usher protein facilitates the transport of the newly assembled pilus across the outer membrane of the bacteria. This process is a key target for the development of new antibiotics, as if biogenesis of new pili can be disrupted the bacteria will be unable to attach themselves to human cells and infection will be much less likely. “We have been working for a number of years to try and understand the process of pili biogenesis and an understanding of this process takes us a step closer to the development of new antibiotics which will successfully treat cystitis – a common and extremely painful condition, as well as other bacterial infections.”
[Posted: April 2013] |
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ISMB's 5th Bi-Annual Retreat - registration now open
April 2013
Registration is open for the 2013 ISMB retreat. The retreat will take place at Robinson College, Cambridge on 3rd and 4th July. For more information and to register, visit the ISMB Retreat webpages.
[Posted: April 2013] |
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Dr Adeline Goulet paper selected as Article of the Month by the French Society of Biochemistry and Molecular Biology
April 2013
A study by Dr Adeline Goulet in the Moores group, “The structural basis of force generation by the mitotic motor kinesin-5”, has recently been published in The Journal of Biological Chemistry (Dec 28 (2012); 287(53): 44654-66.)
Kinesin-5 motors are important in eukaryotes for the formation and maintenance of the microtubule-based, bipolar mitotic spindle. Kinesin-5s have also been of great interest as novel targets for anti-cancer therapies: kinesin-5-specific drugs block mitosis and are in phase II clinical trials. By using cryo-electron microscopy and sub-nanometre resolution structure determination, Goulet et al have visualised ATP-dependent conformational changes in the kinesin-5 motor domain while bound to its microtubule tracks. These structures provide insight into the mechanism of force generation by kinesin-5s. They also present evidence for auto-regulation of motor activity by a kinesin-5-specific loop that acts as a competitive inhibitor to ATP binding. Future work will be directed at understanding the significance of this finding in the context of the mitotic spindle.
The paper has been selected as Article of the month (April) of the Société Française de Biochimie et de Biologie Moléculaire (http://www.sfbbm.fr/index.php?option=com_content&view=category&layout=blog&id=98&Itemid=62). This work is an inter-disciplinary collaboration with Professor Steve Rosenfeld at the Cleveland Clinic, and was funded by the BBSRC.
[Posted: April 2013] |
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Professor Steve Perkins receives MRC, EPSRC-NSF and Alexion grants
April 2013
Congratulations to Prof Steve Perkins, who has been awarded the following grants:
- MRC grant worth £630,000 over 3 years, funding one PDRA
- An EPSRC-NSF grant worth £1.4 million over 4 years, funding up to four PDRAs
- An Alexion grant worth £133,000 over 1 year, funding one PDRA
[Posted: April 2013] |
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Professor Gabriel Waksman receives MRC grant
April 2013
Congratulations to Prof Gabriel Waksman, who has been awarded an MRC grant worth £2,000,000. The grant will fund 3 PDRAs over 5 years.
[Posted: April 2013] |
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ISMB Students in Research Poster Competition
March 2013
On 25th and 26th February, UCL ran a Research Poster Competition which offered graduate students an opportunity to meet, advertise and discuss the innovative research they are undertaking.
Overall 247 students registered for this year's Research Poster Competition (Arts & Humanities, Laws, Social & Historical Sciences – 13; Built Environment, Engineering Sciences, Mathematical & Physical Sciences – 66; Brain Sciences & Life Sciences – 101, and Medical Sciences & Population Health Sciences – 67).
In the Brain Sciences & Life Sciences Group two ISMB students won runner up prizes (£100 each):
Anna Adams, (Kaila Srai Group)
"Exploring New Routes to Labelled Hepcidin"
Susan Andrew, (Richard Hayward Group)
"You are what you eat: host ion scavenging by intracellular Chlamydia trachoma tis"
[Posted: March 2013] |
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Drs Hazel Smith, Andrea Townsend-Nicholson and Suzanne Ruddy receive SLMS Innovation grants
March 2013
Congratulations to Drs Hazel Smith, Andrea Townsend-Nicholson and Suzanne Ruddy on being awarded SLMS Innovation grants. The grants will be used to implement an exciting Chemistry module for Biological Science students; develop interactive online tutorials for Bioscience students and strengthen links with Yale and to produce films that showcase research laboratories to our undergraduate students.
[Posted: March 2013] |
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Welcome to Prof David Lomas
New Dean of Medical Sciences and ISMB Core Member
The ISMB is delighted to welcome as an ISMB member Prof. David Lomas PhD, ScD, FRCP, FMedSci.
David is the new Dean of the Faculty of Medical Sciences at UCL. His research interests are in understanding the mechanisms of diseases caused by protein misfolding, in particular the serpinopathies, in order to develop novel therapies.
David chairs the MRC Population and Systems Medicine Board, the Respiratory Therapy Area Board at GlaxoSmithKline, and is Chair of the Research Committee and Trustee of the British Lung Foundation. More recently he has chaired the strategic priorities working group for the NHS 100,000 genome project. David has strong experience in applying structural, molecular, cell and computational biology techniques to address unmet clinical needs. Such interface work is increasingly important but it can be challenging for clinicians and scientists, who often work in isolation from each other, to bridge successfully. He is very keen to facilitate such cross-talk between researchers in the ISMB and UCL-affiliated clinicians. Examples of this might include arranging access to relevant ex vivo clinical samples to further test hypotheses supported by in vitro data, or discussing relevant clinical applications of a novel technology. David is happy to be contacted with ideas for such interactions (d.lomas@ucl.ac.uk). They fit within his broader strategy whereby UCL’s internationally prestigious hospitals will actively partner with new (and existing) world-class scientific institutes to optimise biomedical research at all levels.
Links
[Posted: March 2013] |
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Professor Gabriel Waksman receives ERC Advanced Grant
February 2013
Congratulations to Professor Gabriel Waksman, who has been awarded a ERC Advanced Grant of just over £2 million for the project, 'Structural biology of Legionella’s Effectors and Secretion System'. The grant will fund 3 PDRAs over 5 years.
[Posted: March 2013] |
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Extension of the ISMB's Wellcome Trust funded PhD Programme
November 2012
The Wellcome Trust has extended its funding for the ISMB's Interdisciplinary PhD Programme for a further two years. This will allow a further 10 students to enter the funded study programme in 2013 and 2014.
Links
[Posted: March 2013] |
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Professor Elena Orlova receives BBSRC and MRC grants
November 2012
Congratulations to Prof Elena Orlova, who has been awarded a BBSRC grant worth £315,000 over three years with one PDRA and an MRC grant worth £664,000 over three years with two PDRAs.
[Posted: March 2013] |
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Professor Bonnie Wallace receives BBSRC grant
November 2012
Congratulations to Prof Bonnie Wallace, who has been awarded a BBSRC grant worth £685,000 over five years with two PDRAs and a second grant from the BBSRC worth £117,000 over 18 months with one part time PDRA.
[Posted: March 2013] |
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Dr Bibek Gooptu receives an Alpha 1 foundation grant
November 2012
Congratulations to Dr Bibek Gooptu from the Department of Biological Sciences, Birkbeck, who has received a grant worth £120,000 for one PDRA to work in his group for 2 years.
Links
[Posted: March 2013] |
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Prof Elena Orlova receives BBSRC and MRC Grants
November 2012
Prof Elena Orlova from the Department of Biological Sciences, Birkbeck has been awarded two grants to fund the work of Post-Doctoral Research Associates:
- A BBSRC grant worth £315,000 over three years to fund one PDRA
- A MRC grant worth £664,000 over three years funding two PDRAs
[Posted: March 2013] |
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EMBO Conference in May 2013 announced
The Biology of Molecular Chaperones
Requests for registration are now open for an EMBO Conference 'The Biology of Molecular Chaperones: From Molecules, Organelles and Cells to Misfolding Diseases', which will take place in Sardinia next year. Professor Helen Saibil is the organiser of this EMBO Conference, which will be held from 17 – 22 May 2013 at Santa Margherita di Pula, Italy.
The overall theme of the conference series is protein homeostasis - the regulation of protein folding in the cell - and the mechanisms and consequences of protein misfolding and aggregation caused by cell stress, disease and ageing.
Further information
- Further details about this EMBO Conference, including information about how to apply, are available here.
- A poster for this event is available.
[Posted: November 2012] |
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EMBO Practical Course in September 2013 announced
Image Processing for Cryo-Electron Microscopy
We are pleased to announce that the highly successful EMBO Practical Course on Image Processing for Cryo-Electron Microscopy will be run again in September 2013. This 10 day residential course will take place from 3 September – 13 September 2013 at Birkbeck and is supported by EMBO and also by the FEI company, JEOL, Gatan, and LEICA.
The aim of the course is to teach the basic principles and practical aspects of image processing to bioscientists and structural biologists wishing to determine macromolecular structures by cryo electron microscopy (EM). The course will concentrate on processing of single particle images, and will be aimed at advanced PhD students and postdocs using cryo EM images for structural analysis.
Further information
[Posted: November 2012] |
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ISMB Core member promotions
October 2012
Congratulations to the following ISMB Core Members on their recent promotions:
- Dr John Christodoulou (Research Department of Structural and Molecular Biology, UCL) promoted to Reader
- Dr Carolyn Moores (Department of Biological Sciences, Birkbeck), promoted the Reader
- Dr Joanne Santini (jointly affiliated within the ISMB) promoted to Senior Lecturer
- Professor Finn Werner (Research
Department of Structural and Molecular Biology, UCL) promoted to Professor of Molecular Biophysics
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Dr John Christodoulou receives a Wellcome Trust New Investigator Award
August 2012
Congratulations to Dr John Christodoulou
(Research Department of Structural and Molecular Biology, UCL) working
in 'Structural Biology of
Protein Folding on the Ribosome', who was successful in his application
for a
Wellcome Trust New Investigator Award.
Links
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Professor Gabriel Waksman Receives a Wellcome Trust Senior Investigator Award
May 2012
Congratulations to Professor Gabriel
Waksman (ISMB), who was successful in his application for the coveted
Wellcome Trust Senior Investigator Awards. This is a
highly prestigious award made to established scientists at the top of
their fields of research.
Links
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Professor Gabriel Waksman, FMedSci, FRS
April 2012
We are delighted to announce
that on 19 April 2012 Professor Gabriel Waksman was elected to the Fellowship
of
the
Royal
Society. Fellows are elected for life through a peer
review process on the basis of excellence in science. Each year 44 new
Fellows are elected by existing Fellows.
Professor Gabriel Waksman is
an internationally recognized structural biologist and biochemist who
has made important contributions to our understanding of the structure
and function of secretion machines spanning the entire cell envelope,
and has elucidated mechanisms of transport across membranes through
protein channels. In particular he has provided profound insights into
pilus biogenesis and type IV secretion in Gram-negative bacteria,
combining structural and biochemical/biophysical techniques to provide
a detailed understanding of the molecular events taking place during
secretion by these systems. His seminal contributions have assisted
development of novel antimicrobials targeting the secretion process.
Find out more
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New ISMB commentary: EBs Recognize a Nucleotide-Dependent Structural Cap at Growing Microtubule Ends
April 2012
Sebastian P. Maurer, Franck J. Fourniol, Gergő Bohner, Carolyn A. Moores, Thomas Surrey: EBs Recognize a Nucleotide-Dependent Structural Cap at Growing Microtubule Ends. Cell 2012, 149, 371-382, 13 April 2012.
Find out more
- A new ISMB commentary by Dr Michael Gross is available for this article. The original article was published in the 13 April 2012 issue of Cell.
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Featured publication
April 2012
A nanomachine for getting
proteins into working shape
Clare et al.,
ATP-Triggered Conformational Changes Delineate Substrate-Binding and
-Folding Mechanics of the GroEL Chaperonin. Cell (2012),
doi:10.1016/j.cell.2012.02.047
Researchers at the ISMB have analysed thousands of
images to recreate the elaborate movements of a protein “pot” that
encapsulates other proteins and helps them find the right structure and
remain healthy when exposed to stresses, e.g. elevated temperature or
toxins such as alcohol.
Every cell has a variety of
proteins known as molecular chaperones, which, as the name suggests,
specialise on the guidance and protection of the innocent and
vulnerable among their fellow proteins and shield them from undesirable
interactions. Among these, one of the best studied is the bacterial
GroEL-GroES system which takes the shape of two cylindrical pots glued
back-to-back (each pot is a ring of seven molecules of GroEL) and a
matching pair of lids (each made of a ring of seven molecules of GroES).
Previous research had shown
that partially structured protein molecules undergo cycles of binding
and release inside the pot until they emerge with the correct structure
(identified by the fact that its surface no longer displays any of the
oil-like water-repellent chemical groups that should be tucked away in
the core of the structure). Structural analysis had also shown dramatic
differences between the conformations that the GroEL molecules in the
sides of each pot adopt in various functional states, e.g. with and
without a protein inside, or with and without the GroES lid. Just how
these different shapes interconvert remained a mystery, however.
Now Helen
Saibil and her coworkers at Birkbeck College, collaborating with Art Horwich at Yale
University and using the automated electron microscopy facility at
the Scripps Research Institute in La Jolla, have crowned their
long-running structural work on molecular chaperones using electron
microscopy at very low temperatures (cryo-EM) by combining a large
number of snapshots of GroEL-GroES complexes to build a movie that
shows a plausible way in which the seven subunits of each pot tilt,
expand, and twist to change their shapes during the functional cycle of
this chaperone.
The movies (which will be
available as supplementary information on the Cell web site) show
several distinct phases of coordinated movement carried out by the
seven subunits in the same ring, much like a synchronised swimming
team. The movements they describe suggest how the subunits can first
bind the protein inside the cavity, potentially stretch it to undo
incorrectly folded molecules, and then release it to allow it to find
its own structure in the aqueous environment inside the pot. If the
protein still displays water-repellent patches after it is released
back into solution, it will bind to a new GroEL ring and run through
the cycle again. Once it is correctly folded it will be stable in the
cell environment and will carry out its biological function.
“The operation of chaperone
machines is of fundamental importance in the processes that underlie
protein quality control and repair,” says Helen Saibil. “It is these
functions that decline at different rates in different people during
ageing. If we can understand the details of how these machines work and
what determines their level of activity, we may arrive at a better
understanding of age-related, degenerative diseases for which effective
treatments are currently lacking.”
Find out more
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Dr Carolyn Moores' Group Receives an MRC Programme Grant
January 2012
The Moores group has recently been awarded an MRC Programme Grant. The goal of the research programme is reconstitution of the microtubule-based cellular machinery that is essential for neurogenesis, neuronal migration and differentiation. In particular, the group will investigate the activities of the essential doublecortin family of microtubule associated proteins. The regulatory mechanisms of doublecortin family members will be probed using biochemistry, biophysics and structure determination using cryo-electron microscopy. Molecular findings will be placed in a cellular context by visualising the microtubule cytoskeleton within neurons using cryo-electron tomography. This interdisciplinary research will provide insight into the mechanisms and functions of a family of essential neuronal proteins with important implications for human health. |
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Dr Finn Werner recipient of a Wellcome Trust Investigator Award
January 2012
Dr Finn Werner from the ISMB has
received a Wellcome
Trust
Investigator
Award (WT096553/Z/11/Z) for carrying out
'An integrated study of RNA polymerase transcription'. Finn's RNAP
laboratory will continue to explore the molecular mechanisms of
transcription - in particular of complex RNA polymerases - by using
biochemical, biophysical and structural approaches. In addition the WT
investigator award allows the expansion of the RNAP lab into new
disciplines such as genetics and systems biology, including
transcriptomics and whole genome occupancy studies. The award
encompasses £1.4M and will fund three postdoctoral positions for
a duration of five years (2012-2017). The systems biology will be
explored in collaboration with Jürg Bähler from the GEE
department of UCL. Part of the ample funds that are included in the
grant cover costs for the equipment of a small growth and fermentation
facility for hyperthermophilic Archaea at UCL, in particular Sulfolobus
acidocaldarius.
Structural model of the RNAP
elongation complex. The RNAP (grey) -bound transcription elongation
factor Spt4/5 (wheat/red-green) has recruited ribosomal protein S10
(blue) that in conjunction with the mRNA transcript (turquoise) is
ready to recruit the initiating ribosome to facilitate efficient
coupling of transcription and translation. Double stranded template DNA
is highlighted in purple.
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