On mitochondrial DNA research and scientific work in Poland - a conversation with Prof. Carlo Vascotto

For the last weekend of July, we have a very interesting interview with Prof. Carlo Vascotto, one of the group leaders at the International Institute of Molecular Mechanisms and Machines (IMol) of PAN. The professor talks about his research on mitochondrial DNA, his plans for the future, but also about his very positive experience working with Polish scientists, our sense of national belonging and the beauty, modernity and dynamism of Warsaw.

Enjoy your weekend reading over coffee!

How did your cooperation with Poland begin? Was Prof. Agnieszka Chacinskaya the first person you came into contact with?

In 2011, I took a job at the University of Udine as an indefinitely employed scientist, one of the last, since such a position was abolished by the Gelmini Act of 2010, and my research activities focused on the mechanisms of mitochondrial DNA repair. It is not common knowledge, but in our cells, in addition to the genetic material present in the cell nuclei, there is a small amount of DNA circulating in the mitochondria, the organelles responsible for, among other things, energy production in the cell. Mitochondrial DNA can be damaged by endogenous and exogenous substances, leading to malfunctioning of cellular respiration. There are also diseases caused by mutations in mitochondrial DNA. In particular, I was interested in the APE1 protein, which was known to be present in mitochondria and involved in DNA repair, but it was not known how the protein gets into mitochondria. Mitochondria have a complex structure consisting of two membranes, an outer membrane and an inner membrane, separating two distinct spaces: the intermembrane space and the inner matrix, which houses the DNA. So I began to study what we call "intracellular transport mechanisms." I had preliminary data pointing to a possible role for the mitochondrial protein import pathway, first described by Prof. Chacinskaya, in APE1 transport. I wrote her an email, introducing myself, telling her what I do, asking for feedback on my own data and occasionally updating her on my progress. In 2014, I already had clear data pointing to the role of this pathway in APE1 translocation, and only a few experiments were missing to publish a paper about it. That year I had a biotechnology student, Arianna Barchiesi, as an intern in my lab, and I offered her a trip to Agnes' lab for six months to perform these experiments. Arianna won an Erasmus scholarship and was able to go to the International Institute of Molecular and Cellular Biology (MIBMiK) in Warsaw. In June of the same year, Agnes invited me to attend a seminar at the institute: this was my first trip to Poland.

How does collaboration with scientists in Poland compare to your other scientific experiences?

My experience from the beginning was very positive, so much so that we were able to publish a joint paper in 2015. This study could have been the beginning of a new project, and since the topic was of interest to both of us, Agnes offered to host me for a few months to get preliminary data that we could use to write a draft for submission to NCN. I applied for a short-term EMBO grant and worked at MIBMiK from November 2015 to February 2016. Based on the results obtained during this short stay, I submitted a project to the Polonez-3 competition and, to my great satisfaction, it was accepted. The three months I spent at MIBMiK and the following two years, from September 2017 to August 2019, at the CeNT of Warsaw University, gave me the opportunity to meet and interact with many Polish colleagues. This resulted in opportunities for collaboration that led to excellent results. Of the many, I would like to mention in particular the one with my colleague Roman Szczęsny from the Institute of Biochemistry and Biophysics of the Polish Academy of Sciences (IBB-PAN). Roman's lab works on mitochondrial RNA metabolism, and while I was at CeNT we started collaborating on another project, the results of which we published in 2021. Two years ago, I proposed Roman join a consortium of laboratories and industrial partners to present a European project on the study of mitochondrial gene expression under physiological and pathological conditions. To the great satisfaction of all of us, the project was funded (www.mitgest.eu). In addition to this particular case, over the past 7 years I have met many Polish scientists and discovered a scientific community open to exchange and cooperation both nationally and internationally.

What scientific goals have you set for yourself in the coming years?

A recently funded NCN project has given me the opportunity to return to Warsaw and move all my research activities here, including the two European projects in which I participate. IMol-PAN is a modern research institute with high international standards. I am currently just transferring all my research activities and collaborators to IMol, and my main goal at the moment is to get the research group ready to resume all activities from September. We have a number of interesting projects that we are already working on thanks to the funding we have received, as well as some for which I am looking for further funding. More generally, my goal in the coming years is to strengthen my position as a researcher at IMol and expand my network of collaborations both at home and abroad by participating in more European projects.

How is the research related to the latest grant "Quality control of the mitochondrial gene expression system in health and disease" going? What is the goal of the ongoing research?

The project officially began on October 1, 2022. To date, all bureaucratic procedures and the recruitment of 11 PhD students have been completed, and some of them have already arrived at their target laboratories. In the last week of July, the first project meeting will be held with the participation of all project managers, PhD students and other partners. Lectures for students, two technical workshops led by Lumicks and Agilent Technologies, and a professionalization workshop "Engaging in professional development" led by Dr. Helen Hampson of CRAC/Vitae are planned. The goal of this network is to explore the mechanisms involved in the control of mitochondrial DNA quality, homeostasis and expression, and to develop new technical approaches and therapeutic interventions for mitochondrial diseases.

What experience do you have in working with institutes of the Polish Academy of Sciences?

More than positive! In recent years, I have had the opportunity to work with many scientists from the Polish Academy of Sciences both in Warsaw and in other cities. In addition, I have encountered a great deal of openness on the part of my colleagues when it comes to welcoming young Italian students to their laboratories for internships under the Erasmus exchange program. In previous years, I have "facilitated" contacts between students and colleagues at IBB-PAN in Warsaw, and the experience on both sides has been very rewarding.

How do you see your scientific future in Poland? How do you intend to develop yourself?

Poland offers many opportunities both at the national and international level - in particular, I am referring to European funds for so-called "widening countries." In this context, I am preparing a project on ovarian cancer in cooperation with the University of Padova and KU Leuven, which we will present this year in the Horizon Europe Twinning program. The goal of these projects is to increase the institutes' competencies and international visibility through collaboration with renowned foreign universities and research institutes by developing research and training programs for staff. With this project, I hope to support the development of my research group, but also, in a broader context, the institute as a whole.

Did anything surprise you about Poland or the Poles? What was it?

What astonished me from the first time I came to Warsaw, and has also infuriated all those who have visited me here over the years, are the beauty, modernity and dynamism of this city. Being attached to an anachronistic view of Eastern Europe, one is amazed to find oneself in a clean and well-maintained metropolis, where public transportation works perfectly and where it is something normal to see elementary school children riding the bus to school by themselves. Over the years, I have had the opportunity to meet and befriend, many Poles, including those outside my professional circle: they have turned out to be extremely sociable people, in love with Italy and really great experts on my country. One aspect that particularly struck me is the great sense of national belonging and the importance of historical memory. An example is the annual August 1 commemoration of the 1944 Warsaw Uprising - today, several decades later, to honor the event the entire city literally stands still for a minute.