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Could we one day predict which patients will respond well to a specific anti‑cancer drug and which will not? Such predictions could improve care, spare patients intensive treatments, and reduce the emotional impact of treatments that do not work. This question interests researcher Iva Tolić and her collaborators. She aims to address it through her lab’s new research line, which focuses on chemotherapy and the mitotic spindle, a key player in cell division. We met with Iva to learn more about her interest in cell division, her current projects, her connection to synthetic cell research, and much more!

She seeks to connect biology and physics

“Cell division is the most important process in the living world. Without cell division, life as we know it would not exist,” said Iva Tolić.

Iva heads the Laboratory of Cell Biophysics at the Ruđer Bošković Institute in Zagreb, Croatia, where she studies how certain aspects of cell division are orchestrated and regulated. She focuses on the mitotic spindle, a small but essential machine found in the cells of eukaryotic organisms (including yeast, plants and humans), which captures and separates chromosomes before cells divide.

“In our research on the mitotic spindle, we are trying to understand all its parts, how this little machine works, and to connect biology and physics.”

She works in vivo, but has close relationships with researchers working on in vitro reconstitutions

“What we learn from the cell is crucial for selecting its most important parts, understanding them and how they work together, in order to eventually build a synthetic mitotic spindle or an entire synthetic cell.”

Iva collaborates mainly with cell biologists and theoretical physicists, but she is also close to many researchers working on bottom-up synthetic biology (SynCell research). Although her recent projects do not involve in vitro reconstitution, she regularly exchanges ideas with SynCell researchers. It therefore seemed natural for her to join the SynCellEU community.

“I felt I had to be part of this community when I saw the names of people I know and respect, who are my colleagues and who are doing research similar to mine or related to it in some way.”

A new research direction to investigate the effect of chemotherapy on the spindle

“Cell division is an important aspect in cancer research.”

Many chemotherapies target the mitotic spindle. This is the case with Taxol, a drug that stops cell growth. Taxol molecules affect microtubules, which are components found both inside and outside the spindle, but their overall effects on the cell are variable and largely unpredictable. This is also the case with another drug, an inhibitor of the KIF18A protein. The inhibitor preferentially kills cancer cells rather than healthy cells, although it is not yet clear why.

Iva and her collaborators want to understand how chemotherapies that target the spindle actually affect it. “We want to understand what causes cells to die when exposed to these drugs, and what happens to the mitotic spindle in cancer cells that survive. We have several different hypotheses, and we plan to observe directly under the microscope how the spindle behaves under the effect of different drugs.” This new research focus in her lab builds on her ERC Synergy project “Aneuploidy” that she is currently leading together with Geert Kops, Nenad Pavin, and the MIT team.

Iva hopes that her lab’s new findings will support the development of treatments that are better tailored to patients. “Our work could enable us to predict how patients will respond to certain drugs that affect the mitotic spindle, depending on what is happening to their mitotic spindle proteins.”

Recent achievements: a new physical law linking spindle size and chromosome dimensions

“It’s a really exciting discovery, a new law that applies to all spindles.”

With her team and Nenad Pavin as a key collaborator, Iva has proposed a simple model, the Chromosome Crowding Model, which links genome size to spindle size in all eukaryotic organisms.  

“The size of the genome varies among all these organisms, with the largest being 10,000 times larger than the smallest genome, but the degree of compaction remains the same. The spindle must therefore adjust to the dimensions of the chromosomes to capture them all.”

Within Iva’s team: a mentoring style tailored to each individual

“I travel a lot and give talks at conferences, but I try to be present, I follow the work closely, and always brainstorm with my lab members.”

She admits that she doesn’t follow a specific mentoring style. Instead, she tries to adapt to each individual in her team and give them the freedom they need to pursue their own ideas.

“What I look for most in the people I work with is motivation and a genuine love for the work. Everything else can be learned. But if the motivation isn’t there, nothing can replace it.”

Additional information:

• To find out more about Iva, her work and her career, you can read
  • Iva Tolic-Nørrelykke, an interview with Iva in the journal Current Biology (2011)
  • When the Going Gets Tough: Scientists’ Personal Challenges, a short interview in the journal Cell (2014)
  • Who controls the cellular traffic lights? a video created by the Ruđer Bošković Institute
• About the mitotic spindle: Mechanobiology of the Mitotic Spindle – YouTube video