From meteorites to multipolar mitosis

An opportunity to join a biology lab to develop their microscopy systems opened a door to this physics Master's student into the world of biophysics research, and has allowed him to start a PhD exploring multipolar mitosis.
From meteorites to multipolar mitosis

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My academic journey started outside of my current lab when I was working on my Master's thesis. Under the guidance of Dr. Sc. Vedran Đerek from University of Zagreb, I conducted research on the classification of meteorites using laser-induced breakdown spectroscopy. This was my first real experience in scientific research, where I got to do experiments, analyze data, and write my thesis. I became captivated by the intersection of physics and biology through the expertise of my mentor, who specialized in bioelectronics.

While I was working on my thesis, I came across a job posting by Prof. Iva Tolić from Ruđer Bošković Institute. She needed someone to take care of and improve various microscopy systems. Drawing from my experience with diverse spectroscopy techniques during my Master's, I envisioned microscopy systems, coupled with biophysics, as an intriguing trajectory for my career. With my mentor's encouragement, I decided to pursue the opportunity.

From the outset, Prof. Tolić was pleased with my eagerness, particularly my enthusiasm for joining a predominantly biologist-led group. While initially considering a job focused on maintaining and developing microscopy systems as per the job posting, my ultimate aspiration was to pursue a PhD in biophysics. I presented this idea to her, and she viewed it as a perfect match for her lab. And so, my journey towards a PhD in the multidisciplinary field of biophysics commenced.

As I lacked sufficient understanding of biology and its application in physics, I attended several workshops to bridge this gap. One of workshops that I could recommend to all students, especially those unfamiliar with biology, is the "Visualising Life – Interdisciplinary Approaches to Biology" workshop at EMBL Heidelberg. This workshop provided an excellent opportunity to gain insight into various interdisciplinary aspects of biology, presented by top experts in the field. Additionally, it served as a valuable platform for networking with students from diverse backgrounds worldwide, which is really important in this job.

Soon it was time for me to start my scientific research. Before I could begin with any research I needed to catch up with the basics on cell biology. I learnt it from various books and papers, and I held journal clubs to get a better understanding of the field, where my colleges helped me a lot with discussions.

Also with the help of my colleagues, I got more proficient with cell cultures and soon after I joined my colleague Monika Trupinić with her project of spindle adaptation to external forces. With her help I went through the whole experimental process, from preparing cell cultures, various cell treatments, microscopy imaging fluorescently labeled cells, image analysis, making different plots based on research interest, etc. In the meanwhile, Monika successfully defended her thesis and moved on from the lab, leaving me and a few colleagues to carry on and expand our work on the subject. We're preparing to publish our findings, so hopefully, you'll soon have the chance to read my first scientific paper.

After this brief detour, to catch up with the fundamentals, I dived into my project on exploring multipolar mitosis. This captivating phenomenon of multipolar division holds significant relevance for the early stages of cancer development. Through various mechanisms, cells determine whether to survive or perish, based on their health status. While numerous mechanisms have been observed, no one truly understands them.

This image depicts a newly formed tetraploid cell with bipolar spindle with 4 centrosome that have already gone through transition from tetrapolar state, captured using superresolution microscopy (STED). Specifically, chromosomes (H2B) and centrins are highlighted in cyan, while tubulin is shown in gray.

When I started working at Prof. Tolić lab there were only two microscopes, but after just a few months we got three new microscopy systems. These were exciting times because all three of them were installed at the same time. For me it was an extremely valuable experience since I got a chance to do assembly and installation with top microscopy experts. Fortunately, one microscope is equipped with a cutting-edge technology known as Lattice Light Sheet, obtained through Prof. Iva Tolić's ERC Synergy grant. This advanced microscope facilitated the imaging of large areas of living cells and enabled the real-time observation of relevant phenomena. Additionally, I've employed various other types of microscopes to gain a comprehensive understanding of centrosome clustering, chromosome congression, and the overall distribution of forces within multipolar spindles. Given the complexity of multipolar divisions, I devised creative methods to visualize them through animations and represented various observed variables using diverse types of graphs, enhancing my skills as a data scientist. Watch microscope footage of a centrosome clustering during metaphase of a newly formed tetraploid multipolar cell with multipolar spindle, and an animation I created to illustrate the concept.

Recently, a new postdoctoral researcher joined Prof. Pavin's group, our close collaborators. He brings expertise in theoretical physics, which will be helpful in modeling of multipolar divisions, complementing my experimental work. With our shared physics background, we're about to sprinkle some much-needed logic onto this bewildering biology buffet!

Throughout this exhilarating journey, I've developed a profound passion for the wonders of science. The potential for discovery and contribution to the scientific community fills me with anticipation for the unfolding chapters of my scientific journey.

Lovro Gudlin presenting his work at a conference.

More information on the research? Watch a recording of the talk that Prof. Iva Tolić gave the FEBS Junior Section on the topic of Mechanobiology of mitosis and its role in mitotic fidelity.

All images by Lovro Gudlin.

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