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European Training Network on (+)RNA Virus Replication and Antiviral Drug Development

Final Report Summary - EUVIRNA (European Training Network on (+)RNA Virus Replication and Antiviral Drug Development)

EUVIRNA bridged the gap!
The Marie Curie initial training network EUVIRNA set off in 2011 to train a new generation of entrepreneurial researchers in the field of viral replication and anti-viral drug development. Six excellent academic research groups joined forces with three companies to train 20 young scientists with the challenge to “bridge the gap” between industry and academia. Four years later, EUVIRNA counts its many successes.

PhD degrees and advancement of Postdocs
EUVIRNA aimed to train 17 Early Stage Researchers with the goal to lead to a PhD degree, as well as three Experienced Researchers in an industrial setting. The 17 ESR positions have already yielded three PhD degrees and will be followed by nine PhD degrees in the coming year. Four ESRs will take a bit longer to finish their theses and will probably graduate in 2016 or 2017. This delay is partly caused by the longer PhD programmes in the Netherlands and Belgium, and partly by the later start of these ESRs. Only one ESR has decided not to pursue a PhD in this area, but has received valuable training that will help his further career. On top of that 3 “fresh” Experienced Researchers (“postdocs”) successfully concluded their two-year research period, two of which in an industrial setting. Their training has given them the opportunity to obtain excellent new positions in research or research management.

Training programme
EUVIRNA’s unique training programme consisted of a local hands-on research project and network-wide training activities. The network organised seven one-week network meetings, at which the fellows received intensive training in research skills and complementary skills. During the progress discussions at these meetings, fellows updated each other on their research progress, inspired each other with new research ideas and build bridges between the different research groups. All EUVIRNA courses were very well appreciated. Best evaluated research training workshop was “Advanced Microscopy”, organised by the University Hospital of Heidelberg. This training not only gave an excellent introduction to current microscopy techniques brought by the experts in Heidelberg and beyond, it also gave excellent examples of the potential of those techniques by giving very relevant examples. The complementary skills workshops were also very well appreciated. For example, an extra workshop “Team Skills” was organised and received an excellent evaluations. This first training provided the fellows with a view on their own character and of possible ways to interact with others. It has tied the various characters in the training network together to form a team that could work successfully during the following meetings. The fellows considered this workshop “very interesting and unexpectedly entertaining!”

Dissemination
Finally, the workshop on “Dissemination & Societal Outreach” also needs to be mentioned. Highlight during this workshop was a skype session with one of the most renowned virologists in the world, prof. Vincent Racanielo, who is considered “Earth’s virology professor”. During the skype session he gave “100% precise constructive critics” to the EUVIRNA blog the fellows had prepared. The fellows were inspired by his enthusiasm and drive. After the workshop, EUVIRNA ESR Joanna Zmurko has taken up the responsibility for the Facebook page of the Rega Institute of K.U. Leuven, in which she writes about interesting findings in virology and antiviral drug development. Joanna Zmurko also features in the EU Campaign “Science, a girl’s thing!”.

Scientific output
EUVIRNA has delivered important scientific insights, both on the basic aspects of RNA virus replication as well as in the field of antiviral drug development against these viruses. Examples of new basic insights in RNA virus replication are (i) the identification of a SARS-CoV protein complex that integrates RNA polymerase and exonuclease activities, (ii) structure data that reveal that a specific domain in the arterivirus helicase resembles a cellular helicase involved in nonsense-mediated mRNA decay, and (iii) the finding that glutathion plays an essential role in morphogenesis of a number of enteroviruses (e.g. poliovirus, coxackievirus). These examples also highlight the diversity of techniques and approaches that were used in EUVIRNA (i.e. molecular biology, biochemistry, bioinformatics, structural biology, cell biology, microscopy). Examples of important contributions to the field of antiviral drug development are (i) the identification of a novel capsid binder and a protease inhibitor that block enterovirus 71 replication, (ii) new insight into the mode of action of a novel dengue virus capsid inhibitor, and (iii) novel strategies to inhibit replication of chikungunya and dengue virus infection by using small novel RNA molecules to stimulate the innate immune response. These studies involved screening of small molecule libraries, in silico drug design, medical chemistry, and detailed mode of action studies.

Publications
Thus far, the project has yielded 35 publications in peer-reviewed journals, which include high impact journals such as PNAS (Proceedings of the National Academy of Sciences of the United States of America, 5-year impact factor 10.7) Acta Crystallographic Section D (5-year impact factor 9.4) and Plos Pathogens (5-year impact factor 9.0). For 21 of these publications, the fellow was first or second author. Importantly, 10 of these papers were published as a collaboration between at least two groups of the network, showing the level of interaction between the groups. Publications generally lag behind from the actual work. For this project, it is expected that the total output in peer-reviewed journals will be about 60.

Prizes & Awards
The quality of the fellows can be demonstrated by the high number of prizes and awards they have received during their training period. Fourteen prizes were awarded to the fellows, six of which at the 27th International Conference on Antiviral Research (ICAR) symposium in May 2014 in San Francisco (EUVIRNA’s Final Symposium was organized as a satellite meeting of this large international symposium). At the ICAR symposium, the excellently trained ESRs impressed the ~300 antivirals researchers from around the globe with their posters, their presentations and their questions.

The gap
The ‘gap’ between industry and academia is perceived by both people from the academic sector (“companies only want to make money”) and from the commercial sector (“academics forget the rest of the world”). EUVIRNA brought 6 groups from universities and 3 groups from industry together to bridge the gap and raise a new generation of scientists that can use the strengths from both sectors. The exposure of the fellows to research in industry already changed their mindset and they evolved a much more positive attitude towards working in industry. This is best illustrated by the fact that at the beginning of EUVIRNA only few fellows were thinking of a career in an industry environment, whereas at the end of EUVIRNA the overall majority of the fellows was considering a career in industry!

Secondments
Very well appreciated were the industrial secondments, in which many fellows explored the valorisation potential of their own research results, for example by doing market research or by writing a business plan. During these secondments they were guided by experts from Janssen Pharmaceutica or Aratana Therapeutics. The secondments included a number mentoring discussions via skype and site visits of several days. Other fellows got in depth knowledge and hands-on training in searching and filing patent applications, which was organised by Riboxx GmbH. Importantly, the four ESRs and two ERs who performed their training in an industrial setting also performed fruitful secondments in academic groups, thus exposing them to both sectors.

Careers in Research
The last training of the network was titled “careers in research”. The guidance in writing a good CV and interview training were regarded very useful. Even more useful were the presentations from the industrial partners about the key attributes of ideal candidates for industrial positions: motivation, flexibility and team work. Whereas motivation is an intrinsic value that cannot be trained, the other two attributes were an important part of the EUVIRNA training programme.

The Future
Time will tell whether these fellows will indeed become the leaders of the next generation virology researchers. Surely, they have received excellent training to give them an excellent start of a research career and a network they can use for future collaborations. The partners have also experienced the network very positively and most partners have jointly embarked on a new Marie Sklodowska Curie European Training Network, called ANTIVIRALS (www.antivirals-etn.eu) to further “bridge the gap”.

Contact details:
Website: www.euvirna.eu
Coordinator: Prof. dr. Frank van Kuppeveld
E-mail: antivirals-etn@uu.nl