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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.

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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/

Cryo-EM data collection at eBIC, Diamond UK

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On 2nd to 4th March, Pasi and Benita visited electron Bio-Imaging Centre (eBIC) at diamond synchrotron, UK. Two sessions worth of data was collected on FEI Krios equipped with post-GIF Gatan K2. Data is currently being processed at CSC and is proving to be of superb quality!

Visit from Hagelstamska skolan ninth grade students

Hello,

We are 4 students on the ninth grade with a business idea to make the perfect ice cream with nitrogen. Some of us have had previous experience with the food industry but we should still expand our knowledge about the food industry and the chemistry.

It is very demanding and important that you know everything about these subjects when you make nitrogen ice cream.

There are a lot of safety risks when you are dealing with nitrogen and that is why we couldn’t experiment with it at our school. Instead we got an unique opportunity to go to the research centre in Vik with our Chemistry teacher Katarina Hattula, whom we really want to thank for this opportunity.

At first we went with bus and train to the centre. There we met Pasi who showed us his work station and a little bit of the centre. Pasi also told us everything we needed to know about the nitrogen, for example that it is not dangerous if the subject touches your bare skin for only one second, but if it stays longer you will get serious frostbites. He also gave us the risk analyses, which is very important.

Soon we had put up the cameras and the ice cream experiment began. The center had paid for all the ingredients and it was thrilling to see smoke coming out of the pot. Sadly we couldn’t taste the ice cream because it was made in a laboratorio (you are not allowed to eat in a laboratorio), but Pasi surprised us with ice cream from the store. We got an exclusive interview with Pasi that you can see in our video.

After thanking the friendly staff at the centre we packed our bags and were on our way back to school with a lot to tell our friends.

You can see our video here: https://drive.google.com/a/elev.grankulla.fi/file/d/0B6fIBgaSsq99LU5ySVdOTjg0eEk/view?usp=docslist_api

Thanks to everybody who made this possible!

Amanda, Corinna, Casper and Ina

Hagelstamska skolan

3.2.2016

Sarah Butcher takes up a Professorship in Microbiology from 1st Jan 2016

The Faculty of Biological and Environmental Sciences have hired Sarah Butcher as Professor of Microbiology, and she continues her affiliation with the Institute of Biotechnology (as head of the Structural Biology and Biophysics Programme). On 22nd January she adjudicated over the PhD viva of Teija Ojala (left) with her opponent, Samuel Myllykangas, Blueprint Genetics (middle). The public examination went successfully, pleasing Teija’s two supervisors, Petri Auvinen and Liisa Holm.

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James Geraets demonstrates integration into the Finnish culture

The  annual “pikkujoulu” of the Institute of Biotechnology in early December had two important guest stars, Maija Lepistö as Mamma Santa and James Geraets as Santa Claus, with the big responsibility of spreading joy to the world. This traditional Finnish role was bravely adapted by James, showing how well a Marie Skłodowska-Curie  fellow can integrate into a new culture! santa3santa6

Workshop and AIROPico meeting in Amsterdam

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Members of the group travelled to Amsterdam on 22nd-23rd October for a workshop in 3D cell culture models, and a project meeting of the AIROPico consortium.

The workshop was entitled “The application of human 3D culture models for virus research”. By attending the workshop, new opportunities for academic collaboration were generated, and we also made links with some small biotech firms that have some intriguing products in the development pipeline.

Visit to Electron Microscope Manufacturer

Recently, Sarah Butcher and Laboratory Engineer Pasi Laurinmäki visited the Eindhoven facilities of FEI, an electron microscope manufacturer. They had a tour of the facilities, and were demonstrated the new microscopes and data analysis software. Cleansuits had to be worn in the assembly area!

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Photo courtesy of Pasi Laurinmäki.

BI open day on 2nd October, 2015

Group members of Sarah Butcher’s lab presented their research to undergraduate students from University of Helsinki. The group created models of viruses at 2.8 million times magnification to demonstrate the structure of viruses and their interaction with cells.

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Post doc James Geraets at the poster actively discussing with a student

 

Structural Biology and Biophysics Retreat at Tvärminne

In September, groups from the Institute of Biotechnology (BI) Structural Biology and Biophysics programme descended on the university zoological station at Tvärminne, to spend two days discussing research outcomes, funding applications, and the focus of structural biology research in Finland. It was helpful to relocate to Tvärminne, two hours west of Helsinki, in order to reduce the temptation to spend time in the laboratory during these discussions, and to enjoy the spectacular seaside scenery.

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Photo courtesy of Veli-Pekka Kestilä.

The sauna was great, as was the food and impromptu football match (which was, however, enjoyed more by the spectators than the slightly unwilling participants).