Errors in DNA packaging – PhD defense Jan Dreyer

The genetic information in our cells, the DNA, is located in the cell nucleus. However, it is not just floating around there. Instead, it is carefully organized into a structure called chromatin. This helps to compact two meters of DNA into a tiny nucleus. But chromatin is not just there for storage purposes, it also plays a key role in controlling which genes are turned on and off, thereby affecting the behavior of the cell.

To make sure that this cellular behavior stays stable every time a cell duplicates, not only the DNA must be accurately copied, but the chromatin structure as well. Special proteins, called histone chaperones, assist the cell in rebuilding the chromatin architecture during cell division.

Packaging defects

During his PhD, Dreyer set out to study what happens in human cells when the formation of chromatin goes wrong. “Studying the effects of a defective process can often reveal a lot about how that process normally works,” says Dreyer. By understanding how the cell reacts to errors in DNA packaging, he thus wanted to gain more insight into how chromatin is copied and how histone chaperones work in healthy cells. Additionally, it might bring new knowledge on how changes in chromatin contribute to aging and how errors in DNA packaging contribute to diseases like cancer.

Detection and rescue

Dreyer found out that cells control the packaging of their DNA very carefully, especially during cell division. “Human cells were able to detect problems in DNA packaging surprisingly quickly,” he explains. “As soon as we disrupted this process, the cells reacted immediately, suggesting they have highly sensitive systems to monitor the structure of their genetic material.” How exactly cells can detect and react to these packaging errors is unknown and would be an interesting topic for future research.

Dreyer and his colleagues also discovered that when the main packaging system fails, cells activate backup systems to limit the damage and keep essential functions going. “Understanding these rescue responses offers a unique chance for us to discover new players involved in DNA packaging,” Dreyer says.

Building the foundations

Dreyer’s PhD research gives us a better understanding of how cells maintain the stability of their genetic material and how they respond to errors. This fundamental knowledge helps us understand how our body works and how it responds to stresses. It could also be a first step in studying the role of DNA packaging errors in cancer and whether it is possible to develop new medication that intervenes in this.

Juggling a PhD

Overall, Dreyer looks back on his PhD as a great experience. A real highlight was presenting his research at a Gordon Research Conference in Boston, where an audience full of leading experts in the field gave him valuable feedback on his work. “This experience was both motivating and affirming, and it gave me a strong sense of belonging in the scientific community,” Dreyer remembers.

There were certainly challenges as well. “For example, juggling multiple projects at the same time, while also trying to stay up to date with the literature. This is often difficult to prioritize when there are many experiments and deadlines competing for attention,” says Dreyer. During challenging times, his supervisor Francesca Mattiroli provided steady encouragement, always expressing her confidence that he had what it takes to complete his journey and earn his PhD.

People and science

The continued support from his supervisor and colleagues helped him a lot during the final stretch of his PhD. “For me, the people I work with are more important than the specific research project itself, which will likely evolve over time anyway. My advice to aspiring PhD students would therefore be to choose a PI and group with whom you feel a genuine personal connection. The right environment makes all the difference,” he concludes.