Nikolaus Rajewsky: making sense of the maths of biology

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Leibniz Prize winner Nicholas Rajewsky is setting new standards in systems biology. Quelle: MDC/David Ausserhofer

10.04.2012  - 

At the Max Delbrück Center (MDC), Nikolaus Rajewsky is creatively and fruitfully combining systems biology with physics and mathematics. In doing so, he has set new standards for his branch, and given a boost to the life sciences as a whole. On 27 February in Berlin, his work was recognised by the German Research Foundation (DFG), which awarded Rajewsky with the 2012 Leibniz Prize. At just 43 years of age, he is the youngest of the eleven winners of the award to date. The prize – which covers a range of disciplines, is arguably the most important research prize in Germany; prize money can reach up to 2.5 million euros.

Comprehensible models, clear mechanisms, structures – these things excited Rajewsky even as a teenager. His fascination for physics grew out of a personal favour from a physicist – a four-week special course. However, the field of biology arrived more unexpectedly in his life, no doubt to the satisfaction of Rajewsky’s father, Klaus Rajewsky, a distinguished geneticist and immunologist. The young scientist never expected to become an expert in his field, still less to be end up at the same institution as his father. This came about in 2011 out when Rajewsky junior moved from Harvard University in Boston to the MDC to undertake research into the development of Hodgkin’s lymphoma.

Two paths – one decision

Things could have turned out quite differently. Alongside his studies in mathematics and physics at the University of Cologne, Rajewsky also completed a course in piano at the Essen-based Folkwang School of Music, Dance and Speech, finishing with an “artists graduation”. For a long time, he was unsure which path he should take – that of a scientist, or of a musician. The decision was ultimately a rational one: “If you’re not pretty high up in the success stakes, the musician's life is often a sad one,” the young Rajewsky recognised at the time. Since then, playing the piano has been a private pleasure, and science the focus of his professional interest. He received his doctorate in theoretical physics in the autumn of 1998, and with a grant from the German Research Foundation (DFG), began his post-doctoral studies at Rutgers University in New Jersey – not knowing that he would stumble across the germ of his future career.

In systems biology, researchers work among other things on visualising cellular processes, and then recreating them with computer models.Quelle: M. Zerial/MPI for Molecular Cell Biology and Genetics

A spring feeling in the summertime

Later at Princeton, out of curiosity and on the recommendation of a physicist friend, he took part in a summer seminar on ‘Biology for Mathematicians’. The outcome was the sparking of a new passion in Rajewsky. The physicist and mathematician found himself faced with mountains of quantitative data, newly revealed by innovative technologies. It was a breakthrough – the field of biology, which he had previously spurned, suddenly seemed to make sense. “Instead of to a large extent only describing processes, we could now search for quantitative methods, and mine these masses of data for fundamental principles.” Charged with scientific ambition, Rajewsky saw this as his spring awakening. “I had a feeling of revelation; I really didn’t have to think for long about which path I was going to take. It was a straightforward decision.” Not long after, he moved to Rockefeller University in New York. There, he began a period of intense self-study, whereby the young physicists got to grips with the basic principles of biology: “I read one paper after another, and thanks to the excellent environment at Rockefeller University, I was relatively quickly able to gain an overview.”

Bringing molecular biology to life with computer science

Armed with his newly gained knowledge of molecular biology, Rajewsky began to explore the possibilities of computer science – specifically, taking a close look at the processes of gene regulation. Thereby, his focus was on the events deep inside the cell, and the processes of transcription. This concerns the reading-off and translation in the genome of the protein blueprints – the first phase of protein production.

The test model: the nematode Caenorhabditis elegans.Quelle: www.ucl.ac.uk

Today, Rajewsky is pursuing the question of which factors – as well as how and where – control the reading-off this information, and the effect that this has on the production of proteins. Initially, work focused on the messenger molecule RNA (mRNA), but after moving in 2003 as an assistant professor to New York University, it became clear to the scientist that another, even tinier molecule – so-called microRNA (miRNA) – also played a crucial role in the production of proteins. “The first publications around 2001 indicated that these microRNAs are a complex and huge world, but nobody had an experimental method to hand to determine which genes are regulated by microRNAs,” he explains.

Rajewsky developed a new computational method that enables – in high throughput – the identification of miRNA binding sites in the genome. In pioneering work, he further explored how microRNAs regulate gene activity, thereby controlling the production of thousands of proteins. In the course of his career, Rajewsky has set new standards for systems biology, and even today he considers the full potential of such approaches to be far from exhausted: “If we compare the regulatory networks of different organisms, we might be better able to understand the basic principles, as well as make predictions about these processes.”

The systems biology of microRNAs

Rajewsky is not only interested in pure theory: it is also extremely important to balance the predictions developed with his model with the actual living organism. In his opinion, this is the only means of discovering medically relevant starting points for complex diseases, and for improving the computer models. Now, in collaboration with developmental biologists at the University of New York, he has developed a method for the simultaneously study of large numbers of nematodes in various stages of embryonic development. In cooperation with Canadian and American researchers, he has also created a catalogue of microRNAs from flatworms. In the context of this work, Rajewsky has identified miRNAs that could play a role in the regeneration and function of stem cells. In 2006, Rajewsky began a professorship at the Max Delbrück Center (MDC) for Molecular Medicine in Berlin-Buch.

Here, he will be taking over from predecessor Jens Reich, and helping to construct the Berlin Institute for Medical Systems Biology BIMSB, where he will serve as Scientific Director. Rajewsky is already the third Leibniz Prize winner to join the ranks of the MDC. In a recent interview with the German Zeit magazine, he commented: “The effort that is required to pursue meaningful research has really risen in recent decades,” But one thing has not change: the drive to keep going. “There are still huge mysteries everywhere.”