ABSTRACT
First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping researchers promote themselves alongside their papers. Fabrizia Zevolini is first author on ‘ Polo-like kinase 1 regulates immune synapse assembly and cytotoxic T cell function by driving microtubule dynamics’, published in JCS. Fabrizia is a postdoc in the lab of Cosima T. Baldari at the University of Siena, Italy, investigating cytotoxic T lymphocyte effector functions, with a focus on their killing apparatus and strategies.
Fabrizia Zevolini
How would you explain the main findings of your paper in lay terms?
Chemotherapy is considered the most effective and widely used modality in treating cancers. Polo-like kinase 1 (PLK1) has a key role in cell division and is overexpressed in many types of both solid and blood cancers. A plethora of studies have provided evidence that targeting PLK1 using selective pharmacological inhibitors blocks the proliferation of cancer cells and promotes their apoptosis. In this report, we provide evidence of a new, mitosis-unrelated role of PLK1. We demonstrate that PLK1 regulates a key step in the assembly of the lytic immune synapse, the specialized cell–cell contact that cytotoxic T cells (CTLs) establish with their targets for precise and effective killing. As a result, pharmacological inhibition or genetic deletion of PLK1 suppresses CTL function, highlighting a potential drawback of PLK1-targeted therapies. Our data not only identifies a new player in immune synapse assembly but also underscores the importance of investigating the immune functions of cancer patients undergoing PLK1-directed therapies.
Were there any specific challenges associated with this project? If so, how did you overcome them?
As any lab scientist would expect, I had to deal with many challenges during the development of this project. The toughest and most frustrating were those related to the transfection efficiency of primary CTLs that we generated in vitro from purified peripheral blood CD8+ T cells for all the experiments carried out for this work. Nonetheless, we never gave up, even when we had to start again and again, as we could not always identify the pitfall in the procedure and had to come up with novel ideas. We give thanks to our collaborators for their brilliant suggestions in this difficult period.
When doing the research, did you have a particular result or ‘eureka’ moment that has stuck with you?
The clearest plot twist in this work was when we found that PLK1-inhibited T cells had impaired cytotoxic capability, as this provided evidence that the effects on T cells we had seen when inhibiting PLK1 had a concrete functional outcome.
Why did you choose Journal of Cell Science for your paper?
The Journal of Cell Science is a prestigious journal with highly valuable contributions covering a wide range of fields, hence we expect to reach a broad scientific community with this publication. It is a great pleasure to collaborate with a journal committed to actively support the scientific community. Therefore, we felt this journal was an excellent fit for our work.
Tracking microtubule growth. Time lapse projections of EB1–GFP-expressing T cells plated over anti-CD3- and CD28-coated glass-bottom chambers. Scale bar: 5 µm.
Tracking microtubule growth. Time lapse projections of EB1–GFP-expressing T cells plated over anti-CD3- and CD28-coated glass-bottom chambers. Scale bar: 5 µm.
What motivated you to pursue a career in science, and what have been the most interesting moments on the path that led you to where you are now?
I did not have a clear idea of what my ‘grown-up job’ would be when I was little, but I always knew I wanted to improve other people's lives. During my bachelor's degree in Biotechnologies at the University of Siena, I felt inspired by what I was learning both in the classroom and in the lab; this then motivated me to obtain a PhD in Biology. Another important turning point in my career was doing an internship in the multi-cultured team of Prof. Salvatore Valitutti's lab at the CRCT in Toulouse. Not only did I receive excellent supervision and learning opportunities there, but I also met amazing people and friends.
Who are your role models in science? Why?
Beyond the eminent scientists whose names immediately raise admiration, I am truly inspired by the people I had the pleasure to work with who were only few years older than me. I saw how they could focus on bad results and yet still have the brilliant intuition to proceed with the investigation.
What's next for you?
Based on my personal experience, the greatest professional growth is achieved when sharing knowledge and expertise with other groups, therefore I hope to be able to take part in new projects and collaborate with as many scientists as possible. The fact that I can take part in the progress of scientific research makes me very grateful and willing to proceed in this direction with the greatest enthusiasm.
Tell us something interesting about yourself that wouldn't be on your CV
I strongly believe in teamwork, both in my professional and personal life. I actively participate in my hometown festival ‘Palio dei Ciuchi’, which is a traditional donkey race in which the main districts (‘Contrade’) of the town. This year not only did my paper get published, but my Contrada also won the race!
Fabrizia Zevolini’s contact details: University of Siena, via Aldo Moro 2, Siena, Italy.
E-mail: [email protected]
