Meet Borna Markusic — Visiting PhD student in the Sedlackova lab

Borna Markusic began his scientific journey by earning a Bachelor’s degree in Biochemistry at Saint Joseph University in Philadelphia, USA. There, he secured two scholarships for his early research and received the “Scholastic Achievement” award from the American Chemical Society (ACS) in recognition of his academic excellence. After completing his undergraduate studies, Borna returned to Europe to pursue a PhD at the International Max Planck Research School on Cellular Biophysics (IMPRS-CBP) graduate school, joining the laboratory of Dr. Prof. Ivan Dikic at the University Hospital of Goethe University Frankfurt. Currently, he is a guest researcher in the laboratory of Dr. Hana Polasek-Sedlackova through an EMBO short-term fellowship, where he studies the intersection between DNA replication and autophagy.

• What is your field of expertise? What are you currently working on?

I study cellular quality control systems, which involve a variety of self-regulating activities that maintain a balance between cellular anabolism and catabolism. The two major quality control pathways in the cell are the ubiquitin-proteasome system (UPS) and autophagy. My main focus is on selective autophagy, a form of autophagy responsible for degrading specific substrates or organelles. My current research focuses on elucidating the quality control of MCM helicases during their life cycle to ensure error-free genome duplication. More specifically, I am investigating how selective autophagy influences the biogenesis and recycling of MCM complexes and how this impacts the fidelity of DNA replication in human cells. Our findings will provide insight into the emerging functions of selective autophagy in regulating genomic components and will enhance our understanding of the interplay between cellular proliferation and quality control processes in maintaining homeostasis.

• How did you choose this topic? What do you want to achieve in the future?

I chose this research topic spontaneously, after observing interesting MCM dynamics in a couple of independent proteomic experiments focusing on autophagy. Curiosity led us to explore the potential interplay between autophagy and DNA replication, an area that has been underexplored in the literature. I am now excited to work on this project, as it provides a direct connection between these two biological processes and their implications for maintaining cellular proliferation. In the future, I would like to continue as a researcher in academia and, if all goes well, eventually lead my own research group. At the moment, I am still learning and exploring cell biology, so I am not yet completely sure which field I will specialize in.

• What keeps you fascinated about your work?

I am continuously amazed by the beauty and intricacy of life at the molecular level. It is overwhelming to consider how life took billions of years to form, or to contemplate the countless complex inner workings of the cell. Yet, when research allows us to glimpse even a small piece of this puzzle, it provides an incredible sense of understanding about what we are at the most fundamental level. In this way, working in research never feels boring, as there is always something new to discover each day. Every experiment is another small piece of the puzzle, which can take years to unravel. Of course, patience and persistence are required, and it is easy to become frustrated or discouraged when things do not work out. However, with the right people and environment, the work is usually very stimulating. Lastly, research is a great environment to develop problem-solving skills and creativity.

• Can you briefly share your experience with the application for the EMBO Scientific Exchange Grant?

At the start of my PhD, a colleague in the lab suggested that I consider applying for the EMBO Scientific Exchange Grant, since our lab lacked expertise in DNA replication. After reaching out to Dr. Hana Polasek-Sedlackova, I was grateful that she was enthusiastic about the project and happy to host me in her laboratory. The application process was very clear and straightforward, and the staff at EMBO were extremely helpful in answering any questions that arose.

• Can you share your plans for a research internship at IBP?

During my research fellowship at IBP, we will use state-of-the-art advanced imaging techniques, such as live-cell imaging and quantitative image-based cytometry (QIBC), to study the dynamics of individual MCM subunits. These imaging techniques will allow us to systematically and comprehensively analyze the MCM life cycle and the underlying cellular quality control mechanisms. Additionally, we will use DNA fiber assay experiments to study DNA replication dynamics at the single-molecule level. In this way, we aim to demonstrate the functional consequences of impaired quality control of MCMs on DNA replication and, ultimately, on cellular proliferation.

• How do you maintain your work-life balance? In other words, what do you do when you are not in the lab?

To be honest, I am still in the process of figuring out how to maintain a healthy work-life balance. Nevertheless, in my free time, I enjoy staying active and spending time outdoors by doing various sports. I have also started a band with friends I met in Frankfurt, which I am very grateful for, as I really enjoy playing music.

Photo credit: Dr. Zdeněk Kubát (IBP)