Science is exciting!
An interview with Adriano Aguzzi, Professor of Neuropathology at the University of Zurich
Why Adriano Aguzzi loves team meetings, how he managed to acquire an ERC Advanced Grant for the second time, what he intends to do with the money, and why he thinks that Swiss science will decline if Switzerland and the EU do not find an agreement on the Free Movement of Persons.
You have just returned to your office after your weekly meeting with your team. What happens there?
For me, the weekly meeting is the highlight of the week. This is what I am looking forward to during the entire week, because this is when my lab members will explain what they have done, talk about the results, their interpretations, and what will be the next steps. So this is really what makes me tick as a scientist. I have a wonderful team of committed, clever, hardworking young scientists. It is always a pleasure to listen to them. Today was no exception.
It seems that this morning something excited you particularly?
Well, I am always like that (Aguzzi laughs). Science is exciting!
In 2010 you received your first ERC Advanced Grant (ERC AdG) within the EU 7th Framework Programme. It was completed in April 2015. What was the outcome?
We published around 35 papers, six of them in the top journals Science, Nature, and Cell. There have been almost 1,000 citations of these papers until now and there will be more citations to come. So I would say the scientific outcome of my first ERC AdG has been satisfactory. One might have different standards, but the outcome is reasonable. However, the most important impact is the recognition of scientific talent and the promotion of promising young scientists. This is even more important than our publications. I put a lot of effort into it.
In 2014, you successfully applied for another ERC AdG. What does it mean to you as a scientist to receive an ERC AdG twice?
Well, in essence it means that for the next five years I will not have to worry about how I am going to run my lab. There will be enough money to do that. It takes away all the preoccupation about paying salaries, buying equipment, etc. There is a truckload of money coming; the only thing we have to do is great science, which I think is an incredible privilege.
The focus of your grant is on prions again. What is the scientific goal you wish to achieve?
I try to explain it in a very simple way: If you infect a cell with prions, this cell will replicate these prions very easily. It will amplify the infectious capability of a prion preparation ten thousand fold within a week. When you try to do the same in a cell-free environment, however, it works very poorly. We suggested that the cell contains a machinery that is capable of replicating prions very quickly. I have no idea what this machinery is, but the evidence that it does exist is compelling. So the primary goal of my second ERC AdG is to identify the physical components of this prion replication machinery. Once we have found it, it will satisfy my curiosity – of course. But it is likely that such a machine will also be a target for therapeutic intervention. Once you understand its physical nature, you can invent compounds that will block it and will prevent prion replication.
It does not occur very often that a scientist receives an ERC AdG twice. How did you manage to get it?
I was nervous about the second application, and I tried to maximise my chances. So, I ran a sort of internal competition within the lab. Every one of my co-workers – postdocs, PhD students, even master students – were invited to deliver a one page abstract, saying what they would like to do. Then we went through an iterative process, selecting the most promising ideas, developing them into full proposals and making a coherent story out of them. It was a true team effort. It is not that I sat in my little office and tried to invent something on my own. I really involved the entire team in this.
So the acquisition of the Grant was a team achievement?
Absolutely. Without my team, I would be nobody. This is the way science works today.
You are very experienced with both types of EU science funding, ERC Grants as well as collaborative projects. Where do you see the main differences in managing them?
They are completely different animals. The spirit is totally different. The 7th Framework Programme and Horizon 2020 collaborative projects typically address societal needs. So this is what happens: The EU sets up a questionnaire and asks a bunch of „stakeholders“ about what they think are the important things that science should do in Europe. Stakeholders are often scientists, but of a sort that is politically more well-connected than me. They come up with some fields of activity, and then a call is issued by the European Union. The EU says, we have a problem, which could be pollution, or a disease, or whatever. It then continues to say: “Ok, you scientists make up a consortium with different capabilities.” You apply by stating: “We are good at doing exactly this, and therefore we would like to be funded to solve this problem.” It is similar to what we call „contract research“; there are deliverables, there are milestones – but the research is typically not curiosity-driven. The ERC scheme is completely different. It is the scientist who says: “Look, I have a brilliant idea and I want to put it into practise.” The ERC does not make any restrictions. You can have any kind of ideas. I do not put a value on these two models. They are both needed and important. But they couldn’t be more different from each other.
Based on your experience, what would you recommend to a young scientist who wishes to apply for an EU Grant?
My recommendation is: By all means, apply for an ERC Grant! If successful, this will do wonders to your science and to your career. But the competition is brutal, so you better do the best job you can! I was a referee on the first round of ERC applications at the very beginning. We had 300 grants to award and there were 9‘000 applicants; so the rejection rate was 97%, the success rate 3%. But if you don’t compete, you can be sure that you will not get a grant. Therefore do compete! I am happy to advise any young scientist who considers applying for an ERC Grant. Call me up, send me an email; I am happy to meet and to tell you what I think is a good way of doing these things. Indeed, I have suggested to my friends Fritjof Helmchen and Roland Martin, who were also awarded an ERC AdG, that we should do a round table for scientists of the University of Zurich on „how to win an ERC“. They were enthusiastic about this proposal!
Let us talk about Horizon 2020. Are you happy with the orientation and the design of Horizon 2020?
It’s a compromise. To some extent, I worry that the European Union is putting too much emphasis on applied research. If you look at how big problems have been solved in the past, it has often happened by chance. For example, Howard Temin and David Baltimore were studying tumor viruses in mice that were not of any interest to anybody except a small number of scientists. Yet their research laid the foundation for understanding AIDS, for developing diagnostics tests, and now possibly vaccines. Hence, I think it is a fallacy to believe that all science can be undertaken through an engineering approach, where you say: “Ok, we are here at A. We have to go to B and these are the steps we need to undertake.” Sometimes this approach works wonderfully. And sometimes it fails miserably. I say it again: we need a portfolio of different approaches, but I am a bit worried that the European Union is putting too much emphasis on research that will – allegedly – resolve the problems of humankind.
Currently, Swiss scientists can participate in most programmes of Horizon 2020 as Switzerland counts as a partially associated country. But this partial association will expire by the end of 2016 if Swiss politicians do not find an agreement with the EU on the disputed topic of Free Movement of Persons. What would it mean to Switzerland if there is no agreement?
This development is indeed fateful. Being able to recruit the best scientists from the entire world is always the winning proposition, and Switzerland has understood this for many decades. A big part of our welfare and of our wealth depends on this. At the moment Switzerland is the number one worldwide in scientific productivity, for patent applications, etc. For most indicators we are at the top! Once we are no longer at the top, and this is likely to happen if we are kicked out of the ERC system, we run the risk of entering a spiral of decline which will be very difficult to revert. I have seen this happen in my home country, in Italy. The people are excellent, but no foreigner wants to go to Italy because the research environment is not so good. Therefore the research deteriorates. Consequently, even fewer good people come to Italy. Even Italians working abroad don’t want to move back to Italy if offered a position! All this creates a vicious circle, from which it is almost impossible to escape.
But one could argue that Switzerland can afford to hire the best scientists from all over the world without participating in EU programmes like Horizon 2020.
(Shaking his head) I don’t think this corresponds to reality. Even now it is difficult to hire scientists from outside Europe. Every time I have a brilliant applicant from India or China or even from the United States or Canada, it is incredibly cumbersome to get them a working permit. The Office for Economy and Labor, which is responsible for administering working permits, is unbelievably fiscal and narrow-minded. If these restrictions are also going to apply to European citizens, the attractiveness of Switzerland to scientists from abroad will definitely decline. I think we are shooting ourselves in the foot this way.
Imagine, Switzerland will not find an agreement with the EU. What would this mean to your lab?
I foresee a lot of trouble. I foresee an exodus of talented people, possibly a decline in the scientific output of my lab. I have very clear goals in my mind. I have another 11 years to go until my retirement and I want to reach these goals. In the end, if I cannot reach them in Switzerland because of these things, I also have to draw some conclusions. Switzerland has been great to me. Being an Italian immigrant, I have been living here for more than 20 years and this place has become my home. I am very grateful to the University of Zurich, the canton of Zurich, the University Hospital Zurich and the Swiss National Science Foundation for enabling me to put some of my scientific dreams into reality. I think, what I have been able to do here until now I would not have been able to do anywhere else in the world. But if these truly optimal conditions change, and I will no longer be able to do my work, then I will have to rethink my choices.
You said you still have 11 years to realise your scientific dreams. What would you like to achieve within this timeframe?
Eleven years are not an incredibly long time span! This means that I have to hurry up finding out exactly how prions propagate, how they replicate, how they damage the brain and what we can do against it. These are the goals for the final chapter of my tenure at the University of Zurich.
And you are confident you will reach these goals?
(Laughing) I think if I could get a third ERC AdG I might be able to reach them. And if I were to get a fourth one, maybe the University of Zurich might rethink its retirement ruling and grant me a few extra years!
A morning with Adriano Aguzzi’s team
Thursday is a very special day in the life of Adriano Aguzzi. Every Thursday morning at nine o’clock sharp, he and his team meet for the weekly progress report. Attendance is compulsory for all members of the group. On this bright morning, 24 postdocs, PhD students and co-workers sit at the tables in the meeting room of the University Hospital Zurich with their cups of coffee when Adriano Aguzzi enters. He grabs a coffee as well, rushes to his chair and welcomes his team with a few cheerful remarks. Then the highlight of the day begins: The presentations of new results and insights by the team’s scientists.
The highlights of the day
Today, it is Assunta Senatore’s and Silvia Sorce’s turn (photo on p. 8). They both are postdocs and involved in prion research. Assunta starts by presenting the design and the latest results of her experiments to detect the expression of a mutated prion protein which is linked to genetic prion diseases. She is also trying to develop a new tool that would help to detect and measure this protein. Searching for tools is very typical for research on prions, because suitable methodologies and clever technologies are a prerequisite to reach an understanding of the prion pathogenesis and to ultimately develop a therapy. Assunta’s results appear to be another promising step on the long journey to understanding prion pathology. Adriano Aguzzi reacts quite enthusiastically to her presentation, and a lively scientific discussion ensues among the team before Silvia Sorce begins the second presentation of this morning. She reports on the progress of her longitudinal study in which she is examining what happens in the brain of mice during the course of prion disease. “She has come up with a truly spectacular and unexpected finding”, Adriano Aguzzi reveals to us later when we meet him for the interview. There is another round of intensive scientific debate after Silvia’s presentation, until the meeting closes at eleven o’clock and everybody hurries back to the lab.
Working here opens doors
We take this opportunity to have a short talk with the two postdocs. Assunta Senatore is a biotechnologist, while Silvia Sorce holds a degree in Pharmaceutical Chemistry. They both originate from Italy, but had acquired their PhD in London and Geneva, respectively, before they applied for a postdoc position at Adriano Aguzzi’s lab. Why did they want to come here? Assunta has a simple and clear answer: “This is one of the best labs in the world. Here you may profit from conditions and possibilities you hardly find anywhere else. Having been here opens doors for you.” And Silvia adds: “The equipment and the technical support are excellent. There is a team of brilliant people on all levels. It is challenging to work here, but very inspiring.” Indeed, Adriano Aguzzi has been very successful in attracting promising young scientists as well as in raising funds, which has allowed him to equip his lab with state-of-the-art technologies. He has just installed a brand new device which can do complex screenings of thousands of different samples in a very short time. In addition, he has hired a PhD student who will calibrate and adjust the processes of this new machine. The fact that Adriano Aguzzi has received another ERC Advanced Grant has further heightened the reputation of his lab within the international science community. Asking the two postdocs Assunta and Silvia about their dreams, they both reply that they would like to pursue an academic career. Being successful postdocs in Adriano Aguzzi’s team ensures that they have a realistic perspective to make their dream come true.
Prions are proteins in the bodies of humans and animals. The normal prion protein is important for the maintenance of peripheral nerves, through mechanisms that are still largely unknown. Normally, the prion protein is harmless, but it has a terrible characteristic: It can change its shape and become dangerous. Misfolded prions move from cell to cell and infect other healthy prions causing them to change their shape as well. Finally, a stream of misfolded prions reaches the brain, where they aggregate in neurons and gradually destroy the tissue. Human beings can be infected by pathogenetic prions that enter the body from outside. This happened in the 80’s and 90’s when people ate beef from cattle infected with BSE (Mad Cow Disease). However, prions can also misfold spontaneously. Even after more than 20 years of research, prions have not revealed all their secrets. We still do not know, for instance, which molecules are instrumental to change the shape of prions, and in which way the infected prions damage the brain.
Interview with Adriano Aguzzi
Adriano Aguzzi is Professor of Neuropathology and has been the Director of the Institute of Neuropathology at the University of Zurich since 1998. He is one of the most distinguished specialists on prion pathology in Europe. For more than 20 years, he has engaged in the research of prions and prion diseases like Mad Cow Disease (BSE) and Creutzfeldt-Jakob disease, as well as other neurodegenerative diseases like Alzheimer’s and Parkinson’s disease, where prion-like phenomena play a crucial role. Adriano Aguzzi studied medicine at the Albert-Ludwig-University of Freiburg (Germany), with stints at the University of Basel and at Columbia University (USA). He trained at the University Hospital Zurich and at the Institute of Molecular Pathology in Vienna. In 1995, Adriano Aguzzi established the Swiss National Reference Centre for Prion Diseases. For his pioneering research on prions and prion pathogenesis he was awarded the EMBO Gold Medal (1998), the Robert Koch Prize (2003), the Antonio Feltrinelli Prize (2013), and together with Charles Weismann the Hartwig Piepenbrock - DZNE Prize (2013).
European Research Council (ERC) Grants
Adriano Aguzzi received several SNSF grants and participated in collaborative EU projects. Since his recruitment to the University of Zurich, he has acquired over 47 million CHF in competitive extramural funds. In May 2010, he was awarded an ERC Advanced Grant of 2.5 million Euros for his project “The prion protein in health and disease”. In spring 2015, he received a second ERC Advanced Grant of 2.5 million Euros for the project “Function and malfunction of the prion protein“.