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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.

tvarminne

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).

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Hope for antivirals against parechoviruses

The Butcher, Wolthers and Beaumont labs have recently published an article providing an atomic model of human parechovirus 1. The atomic model was then used to define the epitopes and modes of neutralization for two potential therapeutic antibodies against human parechovirus 1.

Parechoviruses are medically-relevant human pathogens causing mild to severe infections. Currently there are no vaccines or antivirals against them. The Butcher and Wolthers labs as part of the AIROPico consortium in collaboration with the company AIMM Therapeutics, have recently published an article in the Journal of Virology providing an atomic model of human parechovirus 1.

The atomic model was then used to define the epitopes and modes of neutralization for two potential therapeutic antibodies against human parechovirus 1. These human monoclonal antibodies show cross-neutralization against other human parechoviruses as well.

The AM18 antibody recognizes arginine-glycine-aspartic acid motif present on viral capsid protein 1 and neutralizes the virus by competing with the cellular receptor which also recognizes the same motif. The AM28 antibody neutralizes by binding to a conformational epitope and blocking the viral RNA release site.

“This is a first step towards developing therapies against parechoviruses which is one of the long term goals of AIROPico,” says Research Director Sarah Butcher.

The study was supported by the Seventh Framework Programme of the European Union AIPP under contract PIAPP-GA-2013-612308 (AIROPico), the Academy of Finland, the Sigrid Juselius Foundation, the Netherlands Organisation for Health Research and Development, The AMC Research Council, the European Molecular Biology Organization and the European Society of Clinical Virology.

Fab molecules bound to human parechovirus 1.

Picture copyright owned by Pasi Laurinmäki.

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Research Trip to Seili

A few members of the group visited the island of Seili in western Finland between the 17th – 19th of August, in order to attend the 2015 iteration of the Virus-Cell Interactions Symposium, held annually on the island.

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A varied scientific programme was in store, interspersed with sauna and traditional Finnish games. It was a great opportunity to learn about the scientific challenges that our collaborators and colleagues at other universities had been pursuing recently, and also to make new connections with researchers from Finland and further afield.

Highlights included a keynote talk by Ari Helenius about interesting dodecahedron protein quaternary structures, and a boat trip around the archipelago.

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Protobios CSO Toomas Neuman visiting the lab as part of the AIROPICO project

Toomas (Tom) Neuman joined the Butcher lab on January 21st for a two month period to teach us about Protobios, entrepreneurship and life in Estonia. Tom has been busy – one of his first tasks was to join a panel discussion with around 60 PhD students in the ILS winter school on “What does it mean to be a PhD student?” He especially commented on the properties that he as an employer is looking for in industry, including enthusiasm and dedication. Afterwards he joined in round table discussions with the students who were developing new courses for the ILS graduate program, and organising other student events. He has also presented the main idealogy and methods used in Protobios to our Tuesday Biophysics club, which led to a lively discussion amongst the 30 or so technicians, MSc & PhD students, postdocs and principle investigators present. Every week  he holds a workshop with the group to discuss setting up new businesses, brain-storming potential applications and new products. This week he focussed on a more autobiographical approach, going through his own entrepreneur adventures: “An entrepreneur is one who has at least one bankruptcy behind him” was one of his comments to emphasize that in business, as in life, we have to take risks. To introduce him to the cultural life in Helsinki, we visited one of the best “real ale” bars in Helsinki where Tom realised a big difference between Finns and Estonians: Estonians drink vodka and then beer, yet the custom is the opposite in Finland (or maybe just in the Butcher group??).

One of the possibilities that we want to foster through this exchange is not only knowledge on structural virology, but also possible networking for Tom and Protobios in Finland. To further these aims, we have had talks in Turku with Turku University, ArcDia International and Antibody Barcelona (other partners in the AIROPICO project), which have subsequently led to additional contacts with other biotech companies, and researchers in Helsinki University.

Time is flying by, and it is Tom’s last week next week. Time for a few more discussions, report writing and then back home now that all the snow has gone.

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Sir John Walker to give EMBO Keynote lecture in Helsinki, 10th June 2015

The European Molecular Biology Organisation will support a Keynote Lecture by the renowned Nobel Laureate, Sir John Walker during the Paulo Foundation Symposium “From Atomic Structure to Disease Mechanisms” held 10-12th June in Helsinki. Registration is now open for the meeting which is part of the <375> celebrations of Helsinki University.

Sir John’s lecture is entitled “The ATP synthase in mitochondria: involvement in life and death of eukaryotic cells”

Read more about ATP synthase in the Nature Scitable article “Mitochondria”

atpsynthase_4tt3
Ribbons representation of an ATP synthase structure from the PDBe deposition 4tt3, made using UCSF Chimera software. See Bason, J.V., Montgomery, M.G., Leslie, A.G., Walker, J.E. Pathway of binding of the intrinsically disordered mitochondrial inhibitor protein to F1-ATPase. PROC.NATL.ACAD.SCI.USA (2014) 111 pp. 11305 for more details.

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What’s happening in Airopico?

The first year of Airopico, an AIPP action from the FP7 Framework of the EU is coming to a close. We have an active technical board (Katja, Petri, Dirk and Sarah) from 4 of the partners meeting every month to report on scientific progress, exchanges occurring, recruitments, work shops and dissemination. This is a snapshot from one of our meetings. We had an exciting year, with the first papers submitted, a workshop on IPR in Helsinki with some 40 participants, and excellent panelists both from within the consortium and from without. The coming year will see 3 new recruitments, in Turku, Helsinki and Leuven – check out the EURAXESS and the www.airopico.eu sites for posts- we are looking for experienced researchers (4-10 years since start of PhD studies) with less than 12 months of work experience in the last 3 years in the recruiting country (Finland or Belgium). We are looking forward to a bright 2015 with 4 exchanges in to Helsinki from Protobios, and 1 from Helsinki to Protobios. Let the knowledge fly!AttendeeViewerImage001

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International symposium 10-12th June, Helsinki, Finland

The Paulo Foundation Symposium “From atomic structures to disease mechanisms” (10-12th June) in Helsinki aims to bring together structural biologists, biophysicists, drug developers, metabolic diseases, and neurobiologists in a multidisciplinary environment to provoke discussion and present the latest results in these areas. http://www.biocenter.helsinki.fi/atoms2disease/index.html. Funding and support gratefully acknowledged from the Paulo Foundation. the Magnus Ehrnrooth Foundation and Helsinki University <375>.
The satellite Finnish structural biology network meeting will focus on new technical and research advances.

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A new spin on measles virus matrix

Measles is an important disease worldwide that is highly infectious, causing the deaths of over 100000 people annually. We used advanced electron microscopy and image processing methods to make a a three-dimensional model of measles virus. The new model helps to explain many previous, unaccounted for observations in the life cycle of the virus. Measles virus belongs to a family of viruses whose members are all pleomorphic enveloped viruses. All the members of this family contain a so called matrix protein which in measles virus coats the ribonucleoparticle making a “rigatoni-like” helix. More details from the original article by Liljeroos et al in the Proceedings of the National Academy of Science (USA)

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LDL particles and heart disease

LDL particles

Low-density lipoprotein (LDL) particles are the major carriers of cholesterol in the human circulation. They have key roles in both cholesterol physiology and in the development of atherosclerosis. Together with researchers from the Wihuri Research Institute, Aalto University and Oulu University we characterised the structure of LDL particles at the human body temperature to understand the organisation of the lipids and protein that they are made from.See the article for more details
Kumar, V., Butcher, S.J., Öörni, K., Engelhardt, P., Heikkonen, J., Kaski, K., Ala-Korpela, M., Kovanen, P.T. (2011) Three-dimensional cryoEM reconstruction of native LDL particles to 16å resolution at physiological body temperature. PLoS ONE 6(5): e18841. doi:10.1371/journal.pone.0018841.