Decoding the RNA regulome governing cellular stress response and cell fate transitions

What have your Ph.D. studies focused on?

"My PhD focused on RNA-modifying enzymes, particularly pseudouridine synthases, which convert uridine to pseudouridine in ribonucleic acid (RNA). RNA is a key molecule in our cells: some types of RNA carry genetic information from DNA to guide protein production, while others regulate or support different cellular processes. Pseudouridine, on the other hand, is a modified form of uridine, which can affect the structure and function of RNA. So, these pseudouridine synthases play essential roles in gene expression and cellular homeostasis. When these enzymes are dysregulated, they are increasingly linked to disease.

In my research, I uncovered novel functions for PUS10, which is one of these pseudouridine synthases. I found that it regulates the innate immune response by controlling tRNA-derived small RNAs and suppressing endogenous retroelements — and interestingly, these roles are independent of its catalytic activity, what we call a ‘moonlighting’ function. 

First, we investigated how loss of PUS10 affects cells. Using mainly mouse embryonic fibroblasts and confirming select findings in human fibroblasts, we observed activation of inflammatory responses upon PUS10 loss – an effect mediated by a subset of tRNA-derived small RNAs that regulate the expression of endogenous retroelements. Building on these findings and earlier studies identifying PUS10 as a risk locus for inflammatory bowel diseases such as Crohn’s disease, we explored its role in autoinflammatory conditions. In a mouse model of experimentally induced colitis, we found that loss of PUS10 worsened disease severity. We then turned to human datasets and observed reduced PUS10 activity in inflammatory bowel disease and during progression from these conditions to colon cancer. While this is basic research, these findings help improve our understanding of autoinflammatory diseases and suggests PUS10 could potentially serve as a biomarker, benefiting clinical applications.

In addition to this, I also collaborated on work with PUS7, which modifies small RNAs in stem cells and influences translation, with implications for haematopoiesis and leukaemia.

Separately, I contributed to work on ALKBH5, an RNA demethylase involved in a different RNA modification, m⁶A. ALKBH5 regulates RNA splicing and genome integrity during oncogenic transformation, showing that RNA modifications beyond pseudouridine also have critical functions.

Overall, my research revealed new ways in which RNA-modifying enzymes help coordinate cellular responses to immune, genotoxic, and oncogenic stress, highlighting their importance for inflammation, genome stability, translation, and disease."

Can you tell us more about the cover of your thesis?

"The cover of my thesis is an impressionism-inspired depiction of genome disruption and dysregulation alongside the molecular guardians that help preserve proper cellular functions. The partially disintegrating DNA double helix represents the loss of genomic integrity and deregulation events, such as transposable element activation. The surrounding spiral motifs symbolize RNA molecules that play key roles in maintaining cellular homeostasis.

I wanted the cover to capture both the vulnerability and the resilience of the genome – how fragile the balance is, but also how many protective mechanisms exist to safeguard it. To translate that idea into an image, I used DALL·E through Bing Image Creator. It felt like a creative way of visualizing the invisible processes I have spent my PhD studying. 

But you do not want to know how many versions I went through, and how many years I spent working to get it just right. When I began writing my thesis almost two years ago, anytime I needed a break from writing, I would find myself playing with the idea of my thesis cover. Using AI, you really have to know how to prompt it. At one point, I asked ChatGPT to help me refine the prompt for DALL·E so I could get the final image I envisioned. Then came time to choose a color palette, because I wanted something that was colorful and full of life."

How did you end up doing a Ph.D. at Lund University, and the Lund Stem Cell Center?

"I had originally imagined doing my PhD in a German-speaking country, since I had studied there as an exchange student and completed several internships in Germany during my undergraduate education. Also, from my first class of my primary school until high school, I had six hours of German each day. That was also why I thought that studying in a German-speaking country, would be an obvious choice.

However, a close friend of mine began a postdoctoral fellowship at the Lund Stem Cell Center at Lund University, and encouraged me to consider applying there. They spoke very highly of the research environment and of my future supervisor’s group, saying it would be an excellent place for my development. I trusted their recommendation, explored the opportunity further, and ultimately decided to pursue my PhD at Lund University, first joining through the Human Biology Scholarship at the Faculty of Medicine. Looking back, it was the right choice — it has offered me an international, collaborative, and stimulating environment that has helped me grow as a scientist."

What have you found the most enjoyable during your Ph.D. studies?

"What I have enjoyed most during my PhD is the incredible environment at the Lund Stem Cell Center and the many opportunities it offered to stay curious and engaged. I loved attending talks by internationally acclaimed specialists, even in fields outside my own — it was fascinating to see science from different perspectives and think outside the box. I highly recommend researchers from all levels and fields, make use of the opportunities we have to attend these seminars, and join initiatives such as Meet the Expert lunches that are available to us. Coming from a background of reading non-fiction and the history of science, being able to meet and hear from people who are actively creating it has been incredibly inspiring.

I also valued the chance to participate in professional programs, like the Professional Development Program organized by Christine Karlsson and Jenny Hansson, and MentLife by Pernilla Carlsson. These gave me mentors, exposed me to new settings, and helped me grow both professionally and personally.

Finally, living in the Öresund region made it easy to access a wide range of scientific events – from career days to scientific meetings in Copenhagen – where I could always learn something new and meet interesting people. All of these experiences made my PhD journey not just about research, but about broadening my perspective and connecting with the scientific community."

What has been the most challenging aspect?

"One of the most challenging aspects of my PhD came when I faced funding constraints. I had to decide whether to continue working for free while finishing my PhD, or to take on a full-time job and complete my PhD alongside it. I was fortunate to secure a position at the Cell and Gene Technologies Core at the Lund Stem Cell Center, which gave me the chance to learn entirely new operational settings, establish new services, and grow professionally. At the same time, I was working hard to publish my first-author paper. I also dreamed of presenting my PhD work at an international conference, so I applied for several travel grants, fully prepared to fund it myself if necessary. In the end, I secured funding, took time off, and attended my first international conference — which was incredibly rewarding. These last two years were not easy, but they gave me experiences that I hope will continue to shape me as a more resourceful, resilient, and independent scientist."

What are your plans following your Ph.D. defense?

"Currently, I am working full-time at the Cell and Gene Technologies Core at the Lund Stem Cell Center, and I plan to continue in this role after my defence. It allows me to keep learning, contributing, and staying close to the scientific community. At the same time, I want to keep my mind open to future opportunities and see where my skills and experiences can take me."

Any tips or advice for future Ph.D. students?

"I am always cautious about giving advice, because every PhD journey is unique and people are very different. What I can share is what helped me during the most challenging times of my own PhD. I made a conscious effort to keep learning — by attending talks, even (and especially) when they were outside my field, and by expanding my skillset in new directions. I also tried to keep my non-scientific passions alive, because they gave me balance and fresh perspective. For me, nothing has been more valuable than learning to step back, change perspective, and look at things differently" summarizes Magdalena.