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. Artem Fokin is first author on ‘ Inactivating negative regulators of cortical branched actin enhances persistence of single cell migration’, published in JCS. Artem conducted the research described in this article while a postdoc in the lab of Alexis Gautreau at Ecole Polytechnique, Palaiseau, France. His research focuses on investigating the cytoskeleton and everything that moves, both at the intracellular level (vesicular traffic) and at the level of individual cells and cell layers.
Artem Fokin
How would you explain the main findings of your paper in lay terms?
Our body is comprised of zillions of cells, some of which are motile or have migration potential due to the presence of cytoskeleton. The cytoskeleton consists of several systems among which cortical branched actin, which exerts forces at the cell surface, is the main driver of cell migration. We studied the antagonists of cortical branched actin, essentially inhibitors of cell migration, by removing them one by one from cells. Each single depletion resulted in a gain of cell migration, which was not further enhanced upon double depletion, but became much more pronounced when three knockouts were combined in one cell. Additionally, we revealed a checkpoint downstream of cortical branched actin that regulates an epithelial cell state, although the nature of this cell state remains obscure for now. Next, this checkpoint seems to control the level of a cytoskeletal protein called vimentin, which in turn regulates the migration persistence of epithelial cells, but in an opposite manner from its previously understood role in mesenchymal cells. And last but not least, the ‘supermigrator’ phenotype that we observed in triple knockout cells was not the same as the phenotype we observed upon siRNA-mediated depletion of the same proteins, as a result of the involvement of vimentin.
Were there any specific challenges associated with this project? If so, how did you overcome them?
Nowadays, thanks to CRISPR, generation of multiple knockout cell lines is not an insurmountable issue, even though it takes time and requires some patience and meticulousness, while screening hundreds of clones! It was also quite laborious to manipulate many cell lines at once in different experiments, including very complicated ones, but everything was manageable in the end.
When doing the research, did you have a particular result or ‘eureka’ moment that has stuck with you?
Throughout the actual project, we didn't have a particular ‘eureka’ moment during our research, as every new result appeared to be ‘curiouser and curiouser’ to us. But ultimately it was a pleasure to assemble all these seemingly unconnected results into a coherent story.
Why did you choose Journal of Cell Science for your paper?
It was not a difficult choice at all, as I knew that our project, which shows new and interesting aspects of cell migration, and JCS, where cytoskeleton research is traditionally highly represented, were made for each other!
An epithelial cell labelled with antibodies to α-tubulin to visualise microtubules (green), phalloidin to visualise actin (red) and DAPI to reveal the nucleus.
An epithelial cell labelled with antibodies to α-tubulin to visualise microtubules (green), phalloidin to visualise actin (red) and DAPI to reveal the nucleus.
Have you had any significant mentors who have helped you beyond supervision in the lab? How was their guidance special?
When I started my PhD at Moscow State University under the supervision of Elena Nadezhdina, I was infected by her passion for asking interesting scientific questions and looking for the answers. My next supervisor was and is now Alexis Gautreau, to whom I am grateful for a great deal of my success in science and for my professional development. I had also a chance to work for a year in the group of Pascal Silberzan at the Institut Curie, at the interface between biology and physics, through which I learned a completely different way to look at things.
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?
Science is a rare example of an occupation with a high degree of freedom that is not strictly associated with the routine of everyday life. Working in science is a big adventure, which you can enjoy and carry with you throughout your entire life.
What's next for you?
I hope to survive in a very competitive field of academic science and to find a permanent research position.
Tell us something interesting about yourself that wouldn't be on your CV
Despite achieving some modest advances in the field of science, I believe that the most successful experiments I have ever done were with my two children. Making soap from oil, growing butterflies from caterpillars, exploring the physics of the things around us and staring at the distant objects in the sky are already successful experiments whatever the outcome, if I see them curious and full of joy.
Artem Fokin's contact details: Ecole Polytechnique, Route de Saclay, 91228 Palaiseau, France.
E-mail: [email protected]
