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. Ignasi Casanellas is first author on ‘ Substrate adhesion determines migration during mesenchymal cell condensation in chondrogenesis’, published in JCS. Ignasi conducted the research described in this article while a PhD student in Josep Samitier's lab at the Institute for Bioengineering of Catalonia, Barcelona, Spain. He is now a postdoctoral scholar in the lab of Medha Pathak at University of California, Irvine, USA, where he is developing in vitro systems to understand how mechanical environmental inputs guide stem cell functions during tissue formation.
Ignasi Casanellas
How would you explain the main findings of your paper in lay terms?
Our bodies are composed of tissues, such as cartilage, which are formed by stem cells during development. In the early stages of cartilage formation, stem cells move and accumulate into multicellular structures called condensates. This is an important step that sets the structural foundations of the tissue. We know that the way in which cells move over a substrate can be dictated by environmental signals – the stiffness, structure and chemical composition of their surroundings. In our work, we look closely at how the level of adhesiveness provided by the substrate (the ‘floor’) on which cells move mediates the formation of condensates during cartilage formation.
We made 40-h-long videos of stem cells moving (migrating) on substrates that provide different levels of adhesiveness, and we found that cells move very differently depending on how adherent the substrate is, presenting different velocities and directionalities. Moreover, as cells progressively collide and form multicellular condensates, substrate adherence can promote cell–cell attachment (leading to a faster formation of condensates) or detachment (with cells continuing to move individually). This means that, although cells collide more often on substrates of intermediate adherence, condensates grow more quickly on highly adherent substrates.
Our study helps improve our understanding of how tissue development is regulated by the level of adherence between cells and their environment, and can potentially contribute to the development of treatments and regenerative therapies for injured or diseased cartilage.
Were there any specific challenges associated with this project? If so, how did you overcome them?
I had imaged fixed samples before using fluorescence and confocal microscopy, but this was my first time doing live-cell imaging. It was hard to find optimal imaging conditions that would not harm the cells. This all came with technical challenges using the microscope, which took several months to optimize.
After that, perhaps the most challenging aspect was the image analysis. Again, I had previously worked with static samples, but I had never looked at videos in which my subject of study was completely dynamic – not only were cells moving around, but they were colliding, interacting, and changing their shape and structure. There was so much information that could be obtained from these movies, which felt a bit overwhelming. I did a lot of research to determine which parameters would be interesting to look at and did my best to find them out. This was at the height of the pandemic, which came with hurdles (not having as much contact with my lab mates and supervisors) but also advantages (being able to attend the online meetings that started to pop up, such as the Cell Migration Seminars, which were a great learning tool and put me in contact with the wider community).
When doing the research, did you have a particular result or ‘eureka’ moment that has stuck with you?
Every time we managed to make a whole 40-h live video with no issues! After that, progressively getting better with new software and being able to calculate the parameters that we were after.
Why did you choose Journal of Cell Science for your paper?
I had previously read several interesting articles in JCS and loved that the journal is part of a not-for-profit organization. In the end, it really came down to finding a journal with a scope that suited our study, which was somewhere between cell biology and biomaterials, with some bioinformatics.
Have you had any significant mentors who have helped you beyond supervision in the lab? How was their guidance special?
My wife! She's an environmental engineer and scientist. We both finished our PhDs at the same time, almost in parallel. She was not only a great emotional support, but also helped me with R programming and critiqued my writing and presentations. It was hard being almost locked at home for two years (between the pandemic and thesis writing), so I was lucky to be able to share that with such a brilliant person and scientist.
Sequence of mesenchymal stem cells forming multicellular condensates under chondrogenic stimuli. The same two cells are marked with a red and a yellow arrow in each frame. Scale bar: 200 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 think I was drawn to a path where my main job would be producing knowledge for humanity, just trying to understand the underlying mechanisms that essentially rule our everyday life. I never saw myself in an industrial setting or part of a large for-profit corporation. There's a lot that needs to improve in academia, but you can find truly enjoyable experiences in it too, if that's where your interests lie.
It's been 13 years since I started university, and every step has had its highs and lows, but it's hard for me to imagine a more fulfilling line of work. I love working through every aspect of science: from thinking about what questions would be interesting to investigate and what type of experiments would be useful, then figuring out the technical aspects and making it work, to analyzing the data, understanding what it means, writing and – hopefully – publishing.
Who are your role models in science? Why?
I think supervisors (be they PIs, postdocs or even PhD students supervising undergrads) hold a lot more power than they realize when it comes to mentoring. Over the years, I have experienced supervisors who were largely absent, or projected their personal issues and professional frustrations onto their mentees. When you're so young and new in academia, that can have a real negative impact on your career and mental health. On the other hand, I have found excellent supervisors who were actually invested in teaching and helping me to improve. They are my role models, and I think of them whenever I mentor students!
What's next for you?
I just moved across the pond and started my postdoc at University of California, Irvine. I'm working on the mechanobiology of Piezo channels during neural development, while exploring other projects in the lab as well. I do envision staying in academia in the long term and becoming a PI, although that can always change.
Tell us something interesting about yourself that wouldn't be on your CV
I'm a big cinephile, and I almost went for a career in the movies. Finishing high school, my top two choices were science and film school. I might have ended up moving to California either way!
What advice do you have for up-and-coming scientists?
Follow your brain, but also your heart and gut! Pursue the subjects that really interest you, regardless of what is ‘trendy’. Don't be blinded by big names or big papers. Surround yourself with people who will make your life in the lab a good experience and allow you to get better in every aspect of science. Over time, you will build an invaluable set of skills and find the space where you feel comfortable and able to contribute.
Ignasi Casanellas's contact details: Gross Hall (Room 2215), University of California, Irvine, 845 Health Sciences Rd, Irvine, CA 92617, USA.
E-mail: [email protected]
