This event will take place at 4PM in the Aula of the university (Erasmus building, Burgemeester Oudlaan 50, Rotterdam) and is followed by a reception.
The Oncode community is invited to be present at this ceremony. It is not necessary to register in advance, and if you are unable to attend in person, you can also follow the lecture via livestream.
Can you briefly explain what your inaugural lecture is about?
The lecture will cover what I have been doing and what research I will be doing in the future. I will discuss the effects of DNA damage on transcription, which is the main focus of my research group. It is a wide topic, so I will speak about my findings and what led to this research line. I have chosen the title – The Obstacle Course of Transcription – because we think a lot about transcription as a highly regulated process. However, equally important is how the transcription process can handle DNA damage, which is a fact of life, and will form obstacles for transcription. If cells cannot handle that, there won’t be any correct transcription, and this is just as important as transcription regulation. So this is the topic I will dive into, looking at how cells can cope with the DNA damage that inhibits or impedes transcription.
Transcription is the genetic flow from the DNA to the RNA so that our bodies make new proteins. That is a crucial process in the cell. And it somehow mimics those Viking races, where people must overcome different obstacles. In a sense this is exactly what is happening daily with the transcription machinery, and it makes a good analogy: they get on their way, while transcribing the DNA they get different types of obstacles caused by DNA damage, which they must fight and resolve. There are different processes involved how RNA polymerases deal with those damages, and this is what my group is studying and will be studying in the upcoming future.
If you look back at your career so far, what are you most proud of?
I am most proud of studies where we pin down a new factor in the repair pathway. I think one of the ones I am most proud of is the first factor we identified, when I had just started my research group. I worked with my first PhD student on this - Petra Schwertman. We identified the factor that was responsible for UV-sensitive syndrome, causing mutations. We knew for a long time that it was there, but we had no clue which gene was involved. When we found it, we called it UVSSA and we showed that is was a crucial TC NER repair factor. That was the starting point of my research group and it led to several new grants, making my research line more mature.
What do you hope to achieve with your research in the future?
I hope to get a clear idea of what is happening and what the effects of DNA damage on transcription are, and also what factors are involved in its repair. In addition, we don’t know what is exactly happening with the RNA polymerase – the enzyme that translates the DNA itself – when it is stalled at a DNA lesion, and I think that is one of the interesting pursues out there.
It is important for several reasons. For example, that this type of DNA damage is involved in the onset of aging and neurodegeneration, which are important side effects of chemotherapeutics. So, understanding this process might help to reduce the side effects of the commonly used chemotherapeutics.
Another reason is that these RNA polymerases, when stalled at DNA damage, can collide with replication forks resulting in so-called transcription-replication conflicts. These collisions between RNA polymerases, that transcribe the DNA, and DNA polymerases that replicate the same piece of DNA, are an important source of genome instability and can result in the onset of cancer. And we don’t know a lot about it. It is really a new and evolving field. A recent discovery of my lab has shown that ELOF1, is one of the factors that protects against the onset of transcription-replication conflicts. With that finding I hope to get more insights into how these transcription replication conflicts are regulated and recognized and repaired.