Richard Neher

Premier League

Richard Neher, the new professor of Computational Modeling of Biological Processes, recently moved to the Biozentrum. Easygoing and successful describes him well. He has just been awarded the Open Science Prize for his online tool “nextstrain.org”. And with canoe polo he has made it to the German Premier League.

You are investigating influenza and various other viruses. How did you get into this?

My education is actually that of a theoretical physicist. Over the years, however, I became more and more interested in biological questions. This started during my time as a PhD student in Munich with the modeling of single molecule experiments. In the USA, I then drifted in the direction of evolution and designed theoretical models. From there on it was only a small step to start to investigate the evolution of viruses.

And then HIV came into play...

Correct. In recent years we have been investigating HIV. We wanted to understand how it changed over the years in a single individual and in which parts of its structure. Currently, however, we are mostly working with influenza viruses. We analyze their spread and the emergence of new virus variants to describe and predict which of these will prevail in the coming season.

On what do you base your predictions?

We take genome sequences of the viruses, which we obtain from international influenza data bases. Influenza sequencing data is immediately shared and available online. With these data, we can create a phylogeny of the viruses that shows their evolution.

How can these results be used?

The predictions are relevant for the composition of new influenza vaccines. We cooperate with health authorities in the USA. Our results then contribute towards the recommendation for the vaccine composition for the coming year.

So, you predict the type of vaccine for the next flu season?

Not quite. Many different aspects influence this decision. It can happen, for example, that a virus variant is predicted for which there is no virus representative available. In short, it is not always technically possible to produce what the prediction recommends. In addition, you have to be very cautious in the preparation, because a vaccine with a virus variant that changes during production, or does not illicit a good response, can actually do more harm than good.

What makes the influenza virus so successful?

The flu virus’ strategy is to change every year so that people are no longer immune to this new strain, and the virus can then repeatedly infect them. Currently, intensive research is being carried out on a flu vaccine aimed at the invariable regions of the virus in order to permanently cripple the pathogen. That would be the optimal vaccine.

Why is the development of such a sustainable vaccine so difficult?

To persuade the immune system to actually attack the non-variable parts of the virus, instead of those that change easily, is difficult. The virus constantly changes its surface molecules; a similar strategy to that of HIV

Why is it possible to develop an annual vaccine against the flu virus, but not against HIV?

What you have to keep in mind with HIV is that our immune system does not manage per se to get rid of the virus – unlike the flu virus. In addition, HIV is much more diverse, in other words, there are many more genetic variants globally, so it is almost impossible to cover all variants with a single vaccine.

Would it be theoretically possible, to at least develop a vaccine for one of these HIV variants?

That would be possible theoretically, but since one does not know with which virus variant one could come into contact, such a vaccine would not really be helpful.

You use open access data for your computer analyses. What does Open Science mean to you?

For me, it means the open sharing of genetic data, raw data or methods to maximize the benefits to society, reproducibility and data reuse. 

But does this work in practice?

A conflict naturally arises. An individual researcher wants to turn his data into as many good publications as possible and therefore withhold the data for a relatively long period of time. For science as a whole, it would be much better to share results as early as possible. In the past years this issue has once again moved into the spotlight due to the Ebola epidemic in West Africa in 2014, or the Zika epidemic in South America. During this Public Health Crisis all the relevant journals and funding institutions had signed a memorandum saying that all relevant data should be made immediately accessible to the public, and that the prior publication would not be a hindrance to publish a paper at a later date. 

Did this agreement help?

Yes and no. With open access to the data we were able to reconstruct the distribution routes of Ebola and Zika. But despite of this exceptional situation, there have unfortunately been research groups who have withheld their results until their articles were published. 

To what extent could you use your online tool “nextstrain.org” in the case of Ebola?

Within one day, we set up the analysis pipeline for the Ebola virus and all the raw data that was available to us was integrated and analyzed immediately. We were able to track the spread of the virus and, for example, recognize whether and how Ebola infected people were travelling. For example, new virus sequences, which had so far only existed in Liberia, suddenly appeared in Sierra Leone. Such information helps to initiate appropriate preventive measures as well as precautions.

What would be possible future projects?

We started to develop a tool for the spread of pathogenic bacteria. We would like to follow this up at the Biozentrum. For this project I am also in contact with Adrian Egli of the University Hospital. Together, we want to develop a software that can be used to investigate the spread of hospital germs. But there are also many possibilities to network with the infection biologists at the Biozentrum or computational biologists such as Erik van Nimwegen, who is working on E. coli bacteria.

You were also offered a position at the LMU Munich. Why did you decide in the end to come to the Biozentrum?

To be honest, the decision was not easy. I knew Munich already very well. One of the main reasons for my decision was that the Biozentrum is a much bigger, more diverse institute, with a lot of potential points for cooperation that were not really being offered in Munich.

By your lab are still some moving boxes and a paddle...

Since my school days, I have kayaked a lot and have also played canoe polo. In fact, quite intensively. In 1998 we even made it to the German Premier League – which sounds a bit bigger than it really is, in this rather unknown sport. Whilst I was studying in Munich, I did mostly whitewater kayaking. And I know that there is a polo team here in Basel. At some point I will take my paddle and pass by there.

 

Curriculum

Richard Neher studied physics at the universities of Göttingen and Munich, where in 2007, he received his PhD with a thesis on dynamic aspects of DNA. He then pursued postdoctoral studies at the Kavli Institute for Theoretical Physics at the University of California, Santa Barbara. Most recently, Richard Neher was a research group leader at the Max Planck Institute for Developmental Biology in Tübingen, where he began his research on the evolution and spread of viruses. 

nextstrain.org

With “nextstrain.org”, Richard Neher has developed an open access online tool that predicts the spread of viruses and the course of epidemics. In addition to inflenza, HIV and Zika, he also investigated the spread of Ebola. Matthew Cotton (photo center) from the Wellcome Trust Sanger Institute in Cambridge, UK, was in Sierra Leone/Liberia in 2014 and analyzed the data for the affected region directly on the computer with colleagues.