Nikolaus Rajewsky: How a theoretical physicist became a revolutionary

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Back to Germany: Nikolaus Rajewsky, Professor for Bioinformatics at New York University. Quelle: Rajewsky

06.04.2006  - 

Sparking a revolution is not something that Nikolaus Rajewsky had ever contemplated. Nevertheless, the professor at New York University, is regarded as having  begun a revolution in his field in the course of his young career. The 37 year old German develops highly efficiently computer models which analyze molecular activity in the cell nucleus. With the results that the models produce, the bioinformatics expert has turned biology on its head and he is now, among other things, looking for new methods for the treatment of complex diseases. This summer, Rajewsky will be returning to Germany to begin work at the Max Delbrueck Center for Molecular Medicine (MDC) in Berlin.

Comprehensible models, clear mechanisms and structures - Rajewsky was already excited by these things as a teenager. “At some point, I was given a four-week course from a physicist friend of the family, and it just opened my eyes”, he enthuses today. Any interest in biology that he may have had was quickly sidelined. Even Rajewsky’s father, a renowned German geneticist and immunologist now working at Harvard University, was unable to do anything about this. “I was really into Maths and Physics, but biology was incomprehensible. I just couldn’t see any underlying principles, and I opted out of the subject at school during year 10”, remembers Rajewsky, with a chuckle. That he would become a leading figure in this field is something that didn’t occur to him.

Attracted to both physics and music

Nevertheless, after school, science was by no means the only path laid out for him. During his diploma in Maths and Physics at Cologne University, Rajewsky also studied piano at the Folkwang University in Essen. “Back then, I was oscillating between Physics and Music because I was attracted to both worlds”, explains Rajewsky today. Finally, he came to the conclusion that “life as a musician is often a sad life if you’re not in the upper leagues.”

Today, taking pleasure in playing the piano is reserved for more private moments. Professionally, it’s the Natural Sciences that are now taking center-place. He eventually undertook a doctorate in Theoretical Physics, after which, in the autumn of 1998, he moved to Rutgers University in New Jersey to begin a post-doctorate, thanks to a scholarship from the German Research Foundation (Deutschen Forschungsgemeinschaft). Unawares to Rajewsky, this was the beginning of his metamorphosis from physicist to revolutionary.

Innocent beginning of metamorphosis

It all began quite innocently during a summer seminar in ‘Biology for Mathematicians’ in Princeton. He went following a recommendation from a fellow physicist and out of pure curiosity – and was blown away. Rajewsky, the mathematician and physicist, could suddenly see the mountain of quantitative data that, with the help of new technology, could be brought into existence en masse – and the biology just clicked into place. “Instead of just giving an extensive description of biological activities, you could now look for quantitative methods with which this mass of data could be thinned-out, in order to look for fundamental principles.”

Rajewsky’s ambition as a researcher was ignited and now, looking back at those times, he feels it had something about the Wild West about it. “It felt like a revolution had broken out. I didn’t need to think too long about where I was heading - it was as clear as day for me.” He quickly moved to Rockefeller University in New York and began a time of intensive self-study in which the physicist became acquainted with molecular biological principles. “I read one paper after the other and, thanks to the excellent environment at the Rockefeller University, I got an overview relatively quickly.”

Analyzing molecular biology with the tools of informatics

Equipped with new knowledge, Rajewsky took on molecular biology with the tools of informatics, and went through the process of gene regulation with a fine-tooth comb. With this, Rajewsky concentrated on the events deep inside the cell and examined the first phase in the manufacturing of proteins, i.e. the reading of the building plans for the proteins, which are held in the DNA.

The technical jargon for this process is ‘transcription’ and Rajewsky is at the heart of investigations into which factors steer the reading of this information, where and how, and how this all affects the manufacturing of the proteins. Initially, the small molecule messenger-RNA (mRNA) was at the center of his attentions, but, after transferring to New York University as Assistant Professor in 2003, it became clear to him that an even smaller molecule, the so-called microRNA (miRNA), was also playing a decisive role in the production of proteins. “The first publications in 2001 pointed towards the likelihood that these micro-RNAs are a powerful force, but nobody had an experimental method at hand to find out which genes are regulated by miRNA”, he explains.

Tiny molecules regulate human genes

MiRNAs bind with mRNAs and, recent discoveries, to which Rajewsky’s research has contributed, have shown that these tiny molecules regulate at least 30% of all human genes and that they influence essential processes such as the release of insulin and the biosynthesis of cholesterol. In this context, Rajewsky developed a computer model, which allows the identification of the parts of the gene in a high throughput method to which the micro-RNAs bind. “We’re right at the beginning of a long road”, he cautions. Nevertheless, Rajewsky still sees a lot of potential for systems-biological approaches such as this. “Comparing the regulatory networks of the most different living creatures, we can better understand the fundamentals, and make predictions about these processes”.

However, Rajewsky is not only interested in pure theory. The alignment of his modeled predictions with living organisms is extremely important for him. In his opinion, only in this way medically relevant starting-points for complex illnesses can be uncovered and the computer models be improved.

Back to Germany: Intensify medically relevant aspects of his work

With his call on the laboratory for genomic research in Berlin, which was set up by the MDC, together with the Leibniz Institute for Molecular Pharmacology (FMP), Rajewsky, as the successor of Professor Jens Reich, wants to intensify the medically relevant aspects of his work. “I’m looking forward to carry the pioneering spirit of this dynamic branch of research from America over to Germany and Europe”, he says. However, he can’t hide a slight sadness: eight years of research in America has left its mark. “I’m leaving with a heavy heart. I love New York as a city, and there’s such a strong team spirit here at New York University”, confesses Rajewsky. “Notwithstanding, there’s a lot of investment in genomics and systems-biology here in America, and I would find it a shame if Europe was left behind in this field.”

With his move to Berlin, Rajewsky now hopes to contribute to an invigoration of systems-biology in Germany. He was especially attracted by the capital’s excellent reputation as a metropolis for research and culture, as were the MDC’s close connections to scientific research and clinical practice. There were also other more personal reasons for the move: Rajewsky’s wife was born in Iran and, as a professional pianist, she is a frequent international traveler. Unfortunately, due to the current political situation in America, this has become more and more difficult and, for this reason, relocation has been in the pipeline for quite some time.