The fundament of life: how molecules assert themselves against each other

Blue electron cloud of Alu RNA (PDB-ID 5aox) together with the alpha-helix of a protein and a guanine component of RNA
Oliver Weichenrieder together with Christa Lanz (left) and Heike Budde (right) from the Genome Center team

"RNA is not often in the media, but it is the basis of life and evolution. We need to understand how molecules compete against each other. In the end, the organism consisting of the dominant molecules is the one that will prevail." Oliver Weichenrieder enthuses about his research while sitting at his desk. A diffuse cloud of blue dots flickers on the computer screen in front of him: it shows the electron distribution of a molecule that Oliver is currently analyzing.

Oliver Weichenrieder is a structural biologist and head of the Genome Center at the Max Planck Institute (MPI) for Biology in Tübingen. His research focuses on RNA (ribonucleic acid). RNA is a substance that is present in all living organisms and from which life itself probably originally emerged. Simply put, RNA transports the genetic information of DNA and translates it into proteins. The focus of Oliver's research is the so-called "Alu RNA"– a special form of RNA. Similar to a virus, Alu RNA can replicate independently in the cells of higher primates, such as humans, and repeatedly inserts its sequence into the genetic material of these cells. While usually harmless, such integration can also result in fatal consequences, like cancer. "To evaluate and possibly prevent such damage, we first need to understand how these Alu sequences work, where they come from, how they can replicate and how they can integrate into the genome," Oliver emphasizes the importance of this field and adds: "Even before I started my diploma thesis in 1994, I knew that I wanted to find out how Alu RNAs work. Since then, we've learned a lot, but there are still many things to discover.”

Oliver Weichenrieder and Gabriele Wagner from RNA team

A student exchange in 1993 at the University of Boulder in Colorado, USA, sparked in Oliver a fascination about RNA. There, he worked as a scientific assistant in the lab with Jennifer Doudna, who was at the time in Boulder a postdoctoral researcher on RNA and was later, in 2020, awarded the Nobel Prize for the development of the gene scissors "CRISPR-Cas". "Boulder was the capital of RNA research at the time – many fundamental discoveries about RNA were made there, and when I came back to my university in Regensburg after that year, I knew that I definitely wanted to continue conducting research on RNA," Oliver looks back on the beginnings of his scientific career. He then wrote his diploma thesis in Geneva, completed his doctoral thesis in Grenoble, directed his own small research group in Amsterdam for six years, and came to the MPI in Tübingen in 2006. There he worked as a research group leader in the department of Elisa Izaurralde, director at the MPI at that time. In 2018, Elisa Izaurralde passed away prematurely, leaving behind her department in Tübingen. "After Elisa's end, I took care that Elisa's PhD students could complete the projects they had started," Oliver reports of his responsible actions.
Today, he is again mentoring young researchers: from May 2022 on, a master's student has begun her work in his lab, and a doctoral student will join the team in summer. With the two new members and his long-time technical assistant Gabriele Wagner, the size of Oliver's research team will finally after the COVID break come back up to four members.

In his day-to-day work, Oliver spends most of the time doing experimental work on the computer. In addition to planning and evaluating experiments, he supervises the students in his group. Oliver also works as a reviewer for journals and grants, and together with Christa Lanz, he manages the administration of the Genome Center at the MPI for Biology in Tübingen.

When asked about the greatest moment in his career, Oliver doesn't have to think for long: in Grenoble, he managed to create an Alu RNA crystal and make it visible by X-ray structure analysis as an electron cloud. "In this moment, I was the first person in the world to be able to see Alu RNA. That was an incredible", Oliver recalls happily. "It is amazing when the scientists in my group can also enjoy such a moment at some point. The moment when they discover something as the first person in the world, and I get to witness it as a doctoral supervisor," he smiles.

"I hope that we will find out a few more things in the next years," Oliver looks into the future and adds: "The MPI offers a very nice environment with a very diverse research setup, in which I totally enjoy working. Especially as a small group, the collaboration with the other departments at the institute is very important to me." His driving motivation? "Ultimately, you can break all life down to the individual molecules. I want to understand these interactions and thus the underlying principles of life itself."