Martijn Luijsterburg’s Inaugural Lecture | “My dream is that we will be able to see exactly how the cell’s entire repair mach

What is the core message of your inaugural lecture, and why did you choose this topic?

“Our DNA sustains damage every day. For our health, it is important that cells can recognize and repair this damage. I explain this using the metaphor of a genetic railway track.

RNA polymerase is a kind of train that travels along the DNA. This train reads the genetic information and converts it into messenger RNA (mRNA). This is necessary so that cells can do their job.

Sometimes the train encounters damage in the DNA and cannot proceed. This can lead to serious problems, such as cancer, aging, and diseases of the nervous system. By better understanding how cells protect and repair their DNA, we learn more about how our bodies work. This knowledge can also help improve diagnoses and develop new treatments for hereditary diseases.”

What are some of the key areas of research that you and your team are working on?

“Our main research focuses on what happens when RNA polymerase gets stuck on damaged DNA. Over the past ten years, we have discovered several new repair proteins that help with this, including ELOF1 and STK19. These proteins play a key role in removing stalled RNA polymerase and repairing DNA damage. In addition, we are investigating how other proteins, which travel alongside RNA polymerase as it reads the DNA, contribute to protecting the genetic material.

A second important aspect of our research is studying the structure of the entire repair complex. To do this, we use advanced techniques, such as cryo-electron microscopy, which allow us to examine molecules in great detail. This gives us greater insight into how cells protect our DNA and what goes wrong in genetic diseases where DNA damage is not repaired properly.”

What role do education and healthcare play in your vision for this field?

“Through education, we can explain complex biological processes to students and young researchers. Teaching also forces me to keep returning to the most fundamental concepts of the field. That, in turn, helps me in my research.

In the area of healthcare, we collaborate with patient organizations in the Netherlands and other countries. We provide advice on inherited diseases in which DNA damage is not properly repaired. We also assist clinical geneticists by testing patient cells for research purposes, so they can make the correct diagnosis. We work closely with clinical geneticists around the world. As a result, discoveries from basic research can ultimately contribute to better patient care and faster identification of rare disorders.”

What is one thing from the past few years that has really stuck with you?

“That basic research can completely change our understanding of a biological process.

When my research group first started, we knew very little about the proteins that help when RNA polymerase gets stuck while reading DNA. By developing new techniques and combining different research methods, we discovered several new repair proteins. We also now know in detail the sequence in which these proteins work together to repair DNA damage. The moment when you see that separate puzzle pieces come together to form a coherent mechanism remains special. It shows that major progress often does not result from a single spectacular discovery, but from years of patiently building up fundamental knowledge that ultimately yields an entirely new insight.

I have also been struck by how important collaboration is in this process. These discoveries are the result of a close-knit team of researchers tackling complex questions together. The enthusiasm, the shared quest for answers, and the feeling that, as a group, you are solving a scientific puzzle step by step. These elements make research not only successful but also deeply inspiring.”

How do patients and society benefit from your work?

“Our research focuses primarily on the fundamentals of how cells work. Still, it is certainly important to society. By better understanding how DNA damage can lead to disease, we help develop new ways to diagnose and potentially treat diseases. For example, our research has led to the discovery of new genetic diseases caused by DNA not being repaired properly. It has also contributed to treatment recommendations for patients with mutations in the ERCC1 gene. In addition, our knowledge helps doctors recognize rare conditions more quickly and accurately. This is important because it allows patients to receive the right care sooner. Our work demonstrates that basic scientific research not only yields new knowledge but can ultimately contribute to better care and medical innovations.”

If we are allowed to dream, where do you hope this field will be in 10 to 15 years?

“I hope that by then we will have a nearly complete understanding of how reading genes, DNA damage, and DNA repair are interconnected. Many of the processes we are studying were only recently discovered. That is why there are still so many questions we need to answer.

My dream is that we will be able to see exactly how the cell’s entire molecular repair machinery works and how all the proteins involved work together to keep our DNA in good condition. This knowledge is crucial for the medicine of the future. The better we understand how cells function, age, and become diseased, the greater the chance we will find new ways to prevent, detect, and treat diseases.”

Martijn Luijsterburg’s inaugural lecture, “The Vulnerable Code: On Obstacles on the Genetic Track,” will take place on July 6 and can be viewed live via the livestream on Leiden University’s website.