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ISMB News


This page contains recent ISMB News items. Previous ISMB news items are available in the archive.

Latest ISMB Newsletter

The 11th ISMB Newsletter is available to download here: Autumn 2015 news

 

January 2016

Andy Lau wins Poster Prize

Congratulations to BBSRC LIDO rotation student Andy Lau (working with Steve Perkins and Lindsay McDermott) for winning a £100 poster prize for his poster 'Molecular modelling of multiple fatty acid binding pockets in human zinc-α2-glycoprotein' at the 12th Zinc UK meeting held at Ophthalmology on Friday 4th December.

December 2015

Featured Publication

Structure of a bacterial type III secretion system in contact with a host membrane in situ

Many bacterial pathogens of animals and plants use a conserved type III secretion system (T3SS) to inject virulence effector proteins directly into eukaryotic cells to subvert host functions. The purified core complex of the T3SS that is embedded in the bacterial envelope has been extensively studied by single particle analysis and individual protein domains by X-ray crystallography. Despite this, there is still much to discover about the mechanisms of these critical virulence machines, particularly how effectors are recruited to the T3SS in the bacterial cytoplasm and the nature of the interaction with the host membrane. However, the T3SS components mediating these steps are lost during the biochemical isolation of the core complex. We have shown that the intact infectious Chlamydia trachomatis elementary body is small enough to visualise by cryo-electron tomography [Nans A et al (2014)]. This allowed us to visualise the T3SS complexes which are present in an array on one hemisphere of the bacterial surface and to examine the bacteria and the T3SS in contact with a host cell membrane in situ for the first time in any system. Now, we have extended this work by using subtomogram averaging to derive the intact structures of the chlamydial T3SS in the bacterial envelope and in contact with the host cell membrane at ~3.5nm resolution. A comparison of these two averaged structures revealed a marked (~4nm) compaction of the complex spanning the bacterial envelope occurs when the tip of the T3SS apparatus contacts the host cell membrane. This compaction is coupled to the stabilisation of the recently discovered sorting platform-ATPase complex in the bacterial cytoplasm that engages effector substrates. Our findings reveal the first structure of a complete bacterial T3SS from a major human pathogen engaged with a eukaryotic host, and reveal striking ‘pump-action’ conformational changes in the T3SS that underpin effector injection.

This work was funded by the Wellcome Trust.

Nans A, Kudryashev M, Saibil HR and Hayward RD (2015) Structure of a bacterial type III secretion system in contact with a host membrane in situ.

Nature Communications 6: doi:10.1038/ncomms10114 http://www.nature.com/ncomms/2015/151211/ncomms10114/full/ncomms10114.html Nans A, Saibil HR and Hayward RD (2014) Pathogen-host reorganisation during Chlamydia invasion visualised by cry-electron tomography. Cell Microbiol 16:1457-1472

Pathogen-host reorganisation during Chlamydia Invasion

 

November 2015

2nd BPHR Symposium hosted by the ISMB

The 2nd London Postgraduate Research Symposium on Bacterial Pathogenesis and Host Response (BPHR) took place on Friday 27 November at Birkbeck College. The event was hosted by the ISMB for 2015, following the inaugural event at Imperial College in 2014.
The meeting was co-organised by three final year ISMB PhD students Eleanor McMahon (ISMB Wellcome Trust programme in Structural, Computational and Chemical Biology), Charlotte Ford and Oliver Martin (both ISMB MRC programme in Macromolecular Machines of Biomedical Significance) all from Dr Richard Hayward’s group.

Professor Carolyn Moores joins BBSRC pool of experts

Congratulations to Professor Carolyn Moores, who will be joining the Biotechnology and Biological Sciences Research Council (BBSRC) Pool of Experts for 2016.
Members of the pool help to assess research grant proposals and identify the highest quality research for investment.

Dr Richard Hayward receives MRC Research Grant

Congratulations to Dr Richard Hayward, who has received a MRC grant to continue research of the type III secretion system from Chlamydia in collaboration with Professor Helen Saibil. The grant will fund 1 PDRA for three years.

Professor Carolyn Moores receives Worldwide Cancer Research Grant

Congratulations to Prof Carolyn Moores, who has received a Worldwide Cancer Research grant for the project Elucidating Inhibition Mechanisms of Mitotic Kinesin Motors using State-of the-Art Cryo-Electron Microscopy. The grant will will fund 1 post-doctoral researcher (Dr Julia Wenger) for 3 years.

Dr Andrea Townsend-Nicholson receives LIDo Industrial CASE studentship

Congratulations to Dr Andrea Townsend-Nicholson, who has been awarded a LIDo Industrial CASE studentship with Evotec (UK) Ltd, to develop a binding affinity calculator for G protein-coupled receptor drug discovery programmes.
The advertisement for the studentship will be posted in the near future, with an application deadline of 22 January 2016.

October 2015

Dr Maya Topf receives MRC Grant

Congratulations to Dr Maya Topf, who was recently awarded a Research Grant for the project An integrative approach to deciphering the entry process in Herpesviruses. The grant is for 3 years to run until the end of September 2018.

Professor Helen Saibil receives Senior Investigator Award

Congratulations to Professor Helen Saibil who has been awarded a Wellcome Trust Senior Investigator Award for the project, Molecular and cellular mechanisms of protein aggregation and toxicity in models of neurodegeneration, which will run until the end of March 2020.

Professor Elizabeth Shephard receives Wellcome Trust funding

Congratulations to Professor Elizabeth Shephard, who has received a Wellcome Trust Pathfinder Award for the project, Novel metabolite based therapeutics for improved cholesterol, glucose and reduced weight gain.

Professor Kaila Srai appointed Chair of ILSI Expert Group

The ISMB's Professor Kaila Srai has been appointed to Chair one of the International Life Sciences Institute, Europe (ILSI) Nutrient Intake Optimisation Taskforce expert groups, entitled "Interations of Micronutrients with Other Constituents of the Food Matrix ­ What Could Be the Adverse Health Consequences of Changes in BioAvailability?"

The objectives of the Expert Group are available from the ILSI website: Nutrient Intake Optimisation Expert Groups

September 2015

Vitor Pinheiro receives ERASynBio Consortium Grants

Congratulations to Dr Vitor Pinheiro on two successful applications to ERASynBio. ERASynBio is an initiative of international funding agencies working together to promote the robust development of Synthetic Biology and to structure and coordinate national efforts and funding programs.

Grant 1: InvivoXNA - Orthogonal biosystems based on phosphonate XNAs (Top ranked application of the 57 received on the call)
For this grant, Dr Pinheiro is the consortium leader of a 6-lab team involving partners in the US, France, UK and Belgium.
The goal of the project is to create the first XNA system in vivo based on phosphonate XNAs. The total budget of the project is £1677k, of which Dr Pinheiro has been awarded £570k from September 2015 to August 2018, to fund 1 PDRA and 0.5FTE Technician.

Grant 2: TNAepisome - Design and Synthesis of a Bio-orthogonal Genetic System Based on Threose Nucleic acids In Vivo
For this grant, Dr Pinheiro is part of a 5-lab team involving partners in the US, Spain and France. Although the ultimate goal is the same as the invivoXNA, the methodology, target polymerase, chemistry and route to bring the XNA into the cells are all different. This was a slightly smaller consortium, with a total budget of ~EUR1.7M, of which Dr Pinheiro has been awarded £460k from October 2015 to September 2018 funding 1.5FTE technicians.

The BBSRC has encouraged both consortia to collaborate, making UCL the hub for both projects.

August 2015

UCL Biosciences Senior Academic, Research and Teaching Fellow Promotions 2014-15

Congratulations to the following ISMB members who have been successful with academic and research promotions within the UCL Division of Biosciences for 2014/15. The promotions are effective from 1 October 2015.

ISMB Graduate Symposium Prize Winners

Congratulations to Francesco Carbone and Saba Ferdous (both in Andrew Martin's group), who won the best presentation award and best poster awards respectively at the 2015 ISMB Graduate Symposium held in July 2015.

July 2015

ISMB Commentary

A “missing link” in the evolution of transcription machineries

One of the hallmark features of eukaryotic cells is the multiplicity of RNA polymerases (RNAPs). All eukaryotic cells contain three RNA polymerases (RNAP I, RNAP II, and RNAP III) responsible for the transcription of rRNA, mRNA and tRNA, respectively. The core of RNAPI-III transcription machineries shows strong conservation testifying their common evolutionary origin. Other components of the transcription machineries, however, were reshaped throughout evolution to a degree that their origin and functional basis remain obscure.

In their latest paper, Finn Werner’s RNAP lab at the ISMB identified and characterised a new basal transcription factor termed TFEα/β from a distant relative of eukaryotes, the archaeon Sulfolobus solfataricus. Like its RNAPII homolog TFIIE, TFEα/β acts as a basal transcription factor stabilizing the transcription preinitiation complex. Both TFIIE and TFEα/β enhance the initial melting of DNA at the transcription start site as a prerequirement of transcription initiation and consequently TFEα/β stimulates transcription in vitro. Structurally, however, TFEα/β shares some features with its RNAPIII counterpart, the subcomplex hRPC62/39. The most prominent one is a newly discovered iron-sulfur cluster that is essential for the dimerization of TFEα/β. The identification of the iron-sulfur cluster was a collaborative effort of three ISMB groups with EPR-studies in Chris Kay’s lab and native mass spectrometry in Konstantinos Thalassinos’ lab. The combination of several techniques was essential to unambiguously determine the type of cluster being present in TFEα/β. Based on the structural analysis a minimal TFEα/β complex could be identified. Surprisingly, two highly conserved domains of TFEα/β appear to be dispensable for transcription stimulation in vitro, suggesting that these domains become essential in the cellular context where transcription is initiated on chromatinised, topologically restraint DNA.

The new findings deepen our understanding of the evolution and diversity of transcription machineries in archaea and eukaryotes.

Sulfolobus solfataricus TFEα/β interacts with the RNAP via the clamp and stalk modules
Sulfolobus solfataricus TFEα/β interacts with the RNAP via the clamp and stalk modules. The subunit composition of TFEα/β  provides a evolutionary and structural basis for the gain and loss of domains that characterise the evolution of its counterparts in the RNAPII and III transcription machineries.

Original Article: Archaeal TFEα/β is a hybrid of TFIIE and the RNA polymerase III subcomplex hRPC62/39, by Fabian Blombach, Enrico Salvadori, Thomas Fouqueau, Jun Yan, Julia Reimann, Carol Sheppard, Katherine L Smollett, Sonja V Albers, Christopher WM Kay, Konstantinos Thalassinos, Finn Werner (2015): http://elifesciences.org/content/4/e08378

 

June 2015

Award Winning Students

Congratulations to Po-Jung Pao in Professor Steve Perkins' group who was awarded a Biochemical Society Travel Award to attend the ARVO meeting in Denver, Colorado, USA in 3-7 May 2015. Po-Jung was featured in a blog on the Biochemical Society web site.

Congratulations to Ka Wai (Gary) Fung and Orla Dunne, also from Prof Steve Perkins' group, who received prizes at the 15th European Meeting on Complement in Human Disease in Uppsala, Sweden in 27-30 June 2015. Ka Wai received the prize for best poster, for 'The bivalent and co-operative molecular mechanism of Factor H binding to a heparin-coated surface accounts for the onset of inflammatory diseases'. The poster explained how the major complement regulator factor H binds to heparin-coated surfaces on host cells. The poster will be presented as a talk at an ISMB Friday Wrap this Autumn 2015.
Orla won a prize for best abstract for her submission entitled, 'A dimerization site at SCR-17/18 in Factor H may explain its disease-causing mutations and a new mechanism for regulatory control'.

Finally, congratulations to Ms Sayoni Das from Prof Christine Orengo’s group, who received the prize for best poster at the Intelligent Systems for Structural Biology (ISMB/ECCB) Automated Protein Function Prediction SIG meeting in Dublin in July 2015.

 

Amandine Maréchal awarded 5 year MRC Career Development Fellowship

Congratulations to Dr Amandine Maréchal who was recently awarded a MRC Career Development Fellowship for the project Cytochrome C Oxidase: Structure, Function and Malfunction to run until May 2020.

May 2015

Dr Flemming Hansen wins Marlow Award

Congratulations to Dr D. Flemming Hansen on being awarded the 2015 Marlow Award from the Royal Society of Chemistry. The Marlow Award is in recognition of the most meritorious contributions to physical chemistry or chemical physics. Dr Hansen received the award for the development and application of NMR spectroscopy in understanding motions in biological molecules at atomic resolution. 

ISMB members awarded SLMS Teaching Team Award

The team behind the UCL Continuing Professional Development (CPD) course “Lab Techniques in Mammalian Cell Biology” have been awarded a Teaching Team Award by the UCL School of Life and Medical Sciences.

Prof Ivan Gout (Course Lead) and Prof Snezana Djordjevic (Course Director) from the Research Department of Structural and Molecular Biology at UCL and Josephine McNally (Marketing & Communications) from CPD hope to continue their success with further short courses they have in the pipeline.

April 2015

St Mary's School, Buckinghamshire wins 'Creative School of the Year' for "TB or not TB" collaboration with Dr Sanjib Bhakta

Congratulations to Dr Sanjib Bhakta and St Mary’s School, Buckinghamshire (http://www.stmarysschool.co.uk/) on winning the “Creative School of the Year 2015/16” award for their after-school “You Can initiative” Science Project 'TB or not TB' in collaboration with Birkbeck.

The School received a letter from Lord Erroll as well as an invite for them to receive the prestigious award from the House of Lords.

'TB or not TB' is an after-school science project uniquely designed by the Bhakta lab at Birkbeck in collaboration with Mrs Jo Kingston and Mrs Penny Baggott at St Mary’s School, Buckinghamshire, based on the lab's discovery of anti-TB activities in common non-steroidal anti-inflammatory drugs (NSAIDs) and a simple drug susceptibility testing (SPOTi) developed at the laboratory in Birkbeck. See news item from February 2015, below.

The “You Can initiative” project was run by a group of senior girls (Year 11) at St Mary’s School in 2014, funded by the British Institute of Technology and E-Commerce (BITE). As one of the many direct outcomes of the project, the participating students and their Science Teachers Mrs Baggott and Mrs Kingston organised a World TB Day public event in March 2015, at which they gave a group presentation on their laboratory findings with Dr Bhakta in front of a full house. Audience members included a panel of specialist researchers from University labs and local press.
In addition, the group of students created a short film capturing different steps in their project investigation in a very systematic and meaningful way to depict their progression to date.

March 2015

Early Career Research Award for Anthony Roberts

Congratulations to Dr Anthony Roberts, who has been awarded the 2016 'Early Career Research Award: Molecular Structure and Function' from the Biochemical Society.

The Early Career Research Awards are given to outstanding scientists in four different areas, with 'Molecular Structure and Function' as one of the categories in 2016. They recognise scientists for the excellence of their work and the profound impact their research has had on the scientific community and wider society.

The award to Anthony recognises "his research of the highest international standard focused on the structure and mechanism of cellular motor proteins”. His studies, which have relevance to neurological disease, have helped illuminate how one of the least understood motor proteins called dynein moves and is regulated. 

Anthony is invited to give the award lecture at a Biochemical Society conference during 2016, when he will be presented with the Early Career Research Award medal. His lecture will be published in Biochemical Society Transactions.

Anthony Roberts

Image credit: Janet Iwasa

February 2015

Dr Sanjib Bhakta to chair TB Summit at O2 Arena in March 2015

Dr Sanjib Bhakta will be chairing the TB Summit 2015 (24th – 26th March at O2 Arena, Greenwich peninsula, London) organised to commemorate this year's World TB Day.

This international summit organised by EuroSciCon will be in its third year in London. A meeting report will be published to a peer-reviewed journal, as in previous years.

Dr Bhakta will also be delivering a TB Day public lecture and jointly presenting an on-going Science Project with the Year-11 students of St Mary’s School, Buckinghamshire. The School won the “You Can Initiative Award 2014/15” from the British Institute of Technology and E-Commerce on “TB or not TB” led by Dr Bhakta. This project aims towards repurposing existing drugs to treat TB as well as to tackle antibiotic resistance in TB. Dr Bhakta recently wrote a review article entitled “Repurposing - a ray of hope in tackling extensively drug resistance in TB”, which is accepted for publication at the International Journal of Infectious Diseases for a special issue to be published on the World TB Day 2015, jointly organised by UCL-TB and LSHTM-TB.

Dr Bhakta is currently a Reader in Molecular Microbiology at the Institute of Structural and Molecular Biology, Birkbeck, University of London and Honorary Senior lecturer at three research departments of UCL (Research Department of Structural and Molecular Biology, Department of Infection and UCL-School of Pharmacy). He is also a Cipla Distinguished Fellow in Pharmaceutical Sciences and “Antibiotic Action Champion” Member of the British Society for Antimicrobial Chemotherapy. To find more information about Dr Bhakta and ISMB-Mycobacteria Research Lab’s TB research and outreach activities follow: https://www.facebook.com/pages/Dr-Sanjib-Bhakta-PhD-DPhil-Oxford/1402960816587288.

Bhakta_StMarys

January 2015

Dr Giulia Zanetti awarded 3 year Royal Society studentship

Congratulations to Dr Giulia Zanetti from the Department of Biological Sciences, Birkbeck, who has been awarded a PhD studentship by the Royal Society.
The studentship will run for 3 years from 1 March 2015, with research carried out towards the project, 'Mechanisms of Regulation of COPII-Mediated Procollagen Secretion'.

Vacancy: ISMB Lectureship in Infrared Spectroscopy

The ISMB is seeking applications to fill a lectureship in the field of Infrared Spectrosopy. We are particularly interested in (but not limited to) applications of the method to the investigation of biomolecular structures such as electron transfer proteins.

 

 

 

 

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