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Relion – Main Page

Below is link to a Main Page for RELION (for REgularised LIkelihood OptimisatioN, pronounce rely-on) from Sjors Scheres at the MRC Laboratory of Molecular Biology.

http://www2.mrc-lmb.cam.ac.uk/relion/index.php/Main_Page

relion21_tutorial

Grant’s EM course

A series of lectures by Grant Jensen at Caltech explaining cryo-EM technology to a great detail in a simple way:

http://cryo-em-course.caltech.edu/videos/  or  https://jensenlab.caltech.edu/courses/

NRAMM Workshop on Advanced Topics in EM Structure Determination

The talks from The National Resource for Automated Molecular Microscopy (NRAMM) Workshop on Advanced Topics in EM Structure Determination: Challenges and Opportunities (October 29 – November 3, 2017) are available on-line at: http://nramm.nysbc.org/2017-workshop-lectures/. Topics discussed  included specimen preparation, imaging, instrumentation, processing and reconstruction, and methods for validation. 

 

Sarah Butcher awarded Alfred Kordelin prize

The Alfred Kordelin Foundation awarded Sarah Butcher the Alfred Kordelin Foundation prize for her contribution to Finnish science on the 6th November 2017. Link to the announcement in Helsingin Sanomat https://www.hs.fi/kulttuuri/art-2000005437566.html.

Link to the Finnish news in the University web pages https://www.helsinki.fi/fi/uutiset/elamantieteet/alfred-kordelinin-palkinto-professori-sarah-butcherille

Nobel prize in chemistry awarded for method to visualize biomolecules

The Nobel prize in chemistry has been awarded to Jacques Dubochet, University of Lausanne, Switzerland, Joachim Frank, Columbia University, New York, USA, and Richard Henderson, MRC Laboratory of Molecular Biology, Cambridge, UK,

“for developing cryo-electron microscopy for the high-resolution structure determination of biomolecules in solution”

This is very exciting news and fantastic recognition for the whole Cryo-Microscopy Society! The Cryo-EM Unit at the University of Helsinki, headed by Prof Sarah Butcher, hosts state-of-the-art transmission electron microsope FEI Talos Arctica, which enables this technique in its full capacity. We are sure it will prove very useful for  future outstanding research in Finland.

https://www.nobelprize.org/nobel_prizes/chemistry/laureates/2017/press.html

Interview  in C& E News https://cen.acs.org/articles/95/web/2017/10/Cryo-electron-microscopy-innovators-win-2017-Nobel-Prize-in-Chemistry.html

Interview in Helsingin Sanomat https://www.hs.fi/tiede/art-2000005394534.html

Interview about all of the Nobel prizes in Helsingin Sanomat TV https://www.hs.fi/tiede/art-2000005401270.html

History of the high points of the field written by Peter Brzezinski of the Nobel Committee for Chemistry advanced-chemistryprize2017

 

Successful AiroPICO secondments

Justin Flatt joined the lab at the beginning of May as a recruited postdoctoral fellow to continue working on the structural aspects of the Airopico project for one year. He has worked previously with Phoebe Stewart and Urs Greber, primarily on adenoviruses.

Recently we have had Pasi Laurinmäki return from ArcDia International Oy as a secondee in the EU-funded AiroPICO programme. On his return he gave a talk of his experiences in the commercial science world, which was a really interesting perspective.

Urmas Liivas is returning to Protobios OÜ in Estonia after a two-month AiroPICO secondment in our lab. Before he left, he gave a talk about his work and his experience of living and working in Finland. It has been great to have Urmas here, and we will miss him!

Scientists close in on cracking ‘Enigma Code’ of common cold

Our latest work (Shakeel et al Nature Communications 2017; http://rdcu.be/pybT) as reported on www.sciencedaily.com:
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The research findings, published in Nature Communications, revealed the workings of a ‘hidden code’ within the genome of Human Parechovirus, a member of the Picornavirus family that includes the common cold, polio, and hand foot and mouth disease.

The work builds on a discovery made in 2015, when scientists at the Universities of Leeds and York, identified a set of encrypted signals in a plant virus with a single-stranded ribonucleic acid (RNA) genome, not too dissimilar to the structure of the Parechovirus that infect humans and can cause sepsis-like illness and meningitis in children.

They found that the details of the decoding mechanism appear identical in all strains of the virus, potentially allowing a single drug to treat them all, something that is not possible with a vaccine.

The team is now working to screen for potential anti-viral drugs that target this decoding mechanism. Successful future partnerships with the pharma-industry and further funding support could potentially see drug development results within the next ten years.

Professor Reidun Twarock, a mathematical biologist at the University of York’s Departments of Mathematics, Biology, and the York Centre for Complex Systems Analysis, said: “Previously scientists have assumed that the signals regulating the assembly of a virus were located in a unique area of the genome.

“Using a combination of biological insight and mathematical modelling, our study suggests that, by contrast, the mechanism relies on multiple dispersed sites in the genome that act together in a cooperative way to enable efficient virus formation.

“The common cold infects more than two billion people annually, making it one of the most successful viral pathogens, so we are excited to make this crucial step forward.”

Scientists had previously attempted to detect assembly signals by genetically recoding these viruses, but failed to find any. The latest results solve this mystery; they show that the additional ‘hidden’ code, responsible for virus formation, is robust against such genome changes, and is conserved across different viruses in the same family.

Professor Peter Stockley, from the Astbury Centre for Structural Molecular Biology at the University of Leeds, said: “The coding works like the cogwheels in a Swiss watch. We now need a drug that has the same effect as pouring sand into the watch; every part of the viral mechanism could be disabled.

“We need to move away from a vaccine approach, which is what we have for flu and polio. Vaccines, although our best source of defence against polio at the moment, can result in the release of more virulent strains of the disease. Protecting against infection therefore relies on continued worldwide vaccination, which is both very expensive and logistically difficult.”

The World Health Organisation has a goal of eliminating polio infections worldwide via vaccination but recognises that before vaccination can be terminated there is a need to develop anti-polio drugs to cure residual infections.

Professor Sarah Butcher, from the University of Helsinki, said: “This new research means that treatment would be less likely to trigger drug resistance, which is currently one of the major problems in anti-viral therapy. This discovery could be a great leap forward in curing a host of conditions.”
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Source:
University of York. “Scientists close in on cracking ‘Enigma Code’ of common cold.” ScienceDaily. ScienceDaily, 23 February 2017. <www.sciencedaily.com/releases/2017/02/170223092335.htm>.

Link to paper: http://www.nature.com/articles/s41467-016-0011-z; http://rdcu.be/pybT

Reported elsewhere:

http://us.cnn.com/2017/02/23/health/how-to-cure-common-cold/index.html

http://www.abc15.com/news/national/could-the-common-cold-be-cured

CryoEM postdoctoral position

Postdoctoral position in picornaviral structure

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This position is now filled.

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We have an EU-funded position for a postdoctoral researcher to work on picornavirus structure and life cycle using cryoEM and 3D reconstruction. We are looking for an enthusiastic, motivated researcher with a desire to further their expertise in structural virology. 

The position is due to start on 01 April 2017. Applicants should have 4-10 years research experience since qualifying from their MSc degrees. Applicants cannot have worked in Finland for more than 12 months in the three years up to recruitment, and must be eligible for residence and work in the EU. Remuneration will be in the form of a monthly salary of €4477.50, with an additional monthly mobility allowance of between €642.92 and €918.46 depending on family circumstances. The appointment will be made for one year.

Helsinki is the capital of Finland, one of the Nordic countries, famed for its healthy living and excellent (free) education. The Institute of Biotechnology is an independent research institute of the best university in Finland, the University of Helsinki. 

For informal information about the work of the laboratory, contact Dr James Geraets: james.geraets@helsinki.fi

In order to make an application, please send a CV and covering letter to Dr Ram Venkatachalam: r.venkatachalam@amc.uva.nl

http://www.airopico.eu/

 

Become a science sponsor

tiedekummi
Become a personal sponsor for one of the junior researchers in the group. For more information, please see: Sponsorship

One step forward in developing drugs against sepsis-causing virus in newborns

Resolving the high-resolution structure of a parechovirus by Prof Butcher’s group at the University of Helsinki helps the development of antiviral drugs.

Human parechovirus type 3 is a picornavirus that can cause severe infections in humans, resulting in sepsis and central nervous system disease in newborns. So far the most promising anti-picornaviral drug candidates do not have any effect on the parechovirus, therefore new effective means have to be found.

Researchers in the University of Helsinki have determined a high-resolution structure of the human parechovirus type 3. The three-dimensional model was created by collecting thousands of images of virus with an electron microscope under -190 °C. The images were then computationally aligned and combined.

“The virus genome is a single-stranded RNA, which is encapsidated in a protein shell. About a quarter of the genome is in close contact with the capsid proteins, leading to highly ordered RNA. This has not been seen in other picornaviruses,” describes Postdoctoral Researcher, Dr Shabih Shakeel in the Institute of Biotechnology.

The atomic model of the virus shows a distinct way of how viral proteins interact with each other to stabilize the capsid. The best studied anti-picornaviral drug pleconaril and its derivatives work well against enteroviruses, large group of picornaviruses. The parechovirus type 3 structure demonstrates that pleconaril binding place is blocked in parechoviruses and therefore does not work against this virus group.

Marie Curie Postdoctoral Research Fellow, Dr Ausra Domanska worked on the structure of the same virus in complex with antibody fragments recognising parechovirus type 3.

“In the absence of antiviral drugs, developing broadly neutralising monoclonal antibodies as therapeutic antibodies against this virus is one of the most promising treatment options for clinicians in the near future,” she says.

HPeV3-Fab15_ambient_23082016-croped

Human parechovirus type 3 with bound antibody fragments. Picture by Ausra Domanska

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Shakeel, S. et al. Multiple capsid-stabilizing interactions revealed in a high-resolution structure of an emerging picornavirus causing neonatal sepsis. Nat. Commun. 7:11387 doi: 10.1038/ncomms11387 (2016) http://www.nature.com/articles/ncomms11387

This study was supported by Academy of Finland, Sigrid Juselius Foundation, People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme FP7/2007-2013/ under REA grant agreements no. 612308 and no. 628150. The authors of the study, led by Prof. Sarah Butcher at the Institute of Biotechnology, University of Helsinki, and Dr Wolthers at Academic Medical Center in Amsterdam, are all members of the AIROPico consortium.

AIROPico (Academic Industry R&D Opportunities for Picornaviruses) is the first EU-funded scientific consortium for emerging picornavirus research. Coordinated by Dr Katja Wolthers from the Netherlands, AIROPico brings together researchers from two companies and four academic sites across Europe, and aims to shed new light on how picornaviruses cause disease in humans. The consortium’s objectives include the creation of fast point-of-care diagnostic tools and the development of effective anti-picornaviral treatment.

For more info about the AIROPico project see http://www.airopico.eu/