ABSTRACT
First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Marta Grifell-Junyent is first author on ‘ CDC50A is required for aminophospholipid transport and cell fusion in mouse C2C12 myoblasts’, published in JCS. Marta conducted the research described in this article while a PhD student in Prof. Dr Thomas Günther Pomorski's lab at Department of Plant and Environmental Sciences, University of Copenhagen, Denmark. She is now a postdoc in the lab of Tim Cash (CSO) at Senolytic Therapeutics, Barcelona, Spain, a longevity start-up, where she is doing research on senolytic drugs to remove senescent cells involved in age-related diseases.
Marta Grifell-Junyent
How would you explain the main findings of your paper in lay terms?
The generation of skeletal muscle fibers is achieved by cell–cell fusion. Mononucleated myoblasts fuse to form multinucleated myotubes in the primary stages of muscle development. During myoblast fusion, the plasma membrane undergoes lipid topology changes. In our studies, we prove that aminophospholipid flippase activity is downregulated during myoblast differentiation, exposing phosphatidylserine (PS) and phosphatidylethanolamine (PE) on the surface of the plasma membrane. Additionally, we show that the aminophospholipid flippase activity of the myoblasts relies on CDC50A-dependent P4-ATPases. Loss of CDC50A compromises actin remodeling, membrane targeting of the GTPase RAC1 and cell fusion.
Were there any specific challenges associated with this project? If so, how did you overcome them?
The project started in 2015, and from the beginning we planned to prove our hypothesis with knockout cell lines. At the time, the knockout technique CRISPR-CAS9 was very novel, but we lacked expertise. We spent around 2 months talking with professors and expert researchers in CRISPR-CAS9. Next, we struggled for months to generate the knockout cell lines and to demonstrate that they were biallelic knockouts. It was very challenging, but it was also an amazing chance to learn. Luckily for all of us, nowadays there is much more knowledge of CRISPR-CAS9.
When doing the research, did you have a particular result or ‘eureka’ moment that has stuck with you?
As I mentioned, CRISPR-CAS9 was extremely challenging. When we had finally proven that we had knockouts, we brought boxes of chocolate for the whole lab! In the science world, most of the time things are so difficult, we need to celebrate all the small victories!
“…most of the time things are so difficult, we need to celebrate all the small victories!”
Why did you choose Journal of Cell Science for your paper?
We selected Journal of Cell Science for submission because we thought it was a very good journal to explain our story as it covers different fields and aspects of cell biology research. Our studies are based on explaining what is going on during the differentiation from myoblast to myotubes and involved a lot of different levels of cellular biology: from cellular formation, P4-ATPases transmembrane proteins function, lipid arrangement in the plasma membrane, cytoskeleton… JCS was the perfect fit for us.
Deletion of the P4-ATPase flippase subunit Cdc50a results in loss of the aminophospholipid flippase activity and compromises actin remodeling, GTPase RAC1 membrane targeting and cell fusion.
Deletion of the P4-ATPase flippase subunit Cdc50a results in loss of the aminophospholipid flippase activity and compromises actin remodeling, GTPase RAC1 membrane targeting and cell fusion.
Have you had any significant mentors who have helped you beyond supervision in the lab? How was their guidance special?
The research was done in an exceptional lab. For a start, Prof. Dr Thomas Günther-Pomorski was my supervisor but also an extraordinary source of ideas, expertise, and inspiration. Also, Dr Rosa L. López-Marquéz and Dr Sebastian Neumann gave me a lot of feedback and suggestions when I was stuck in my research. Additionally, I was always extremely grateful for the work of the lab technicians and the student helpers. They are the little fairies of the lab! Just magic! Finally, the rest of the PhDs and postdocs, who became my best friends and my family, they were an unconditional personal and scientific support.
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?
When I started to study biology, I wanted to become a marine biologist and dolphin trainer. I always loved nature, animals and the sea. During my studies, I got totally captivated by the complexity of molecular biology and cell biology! All the pathways, mechanisms, genes… and everything working perfectly like clockwork. OMG! I was, and still am, fascinated with all the mechanisms that make us live. My inner curiosity did the rest; I needed to know more about it! I travelled from Barcelona to Copenhagen to do a Master in Biotechnology, and there I met a lot of interesting people. I really liked the university. I enjoyed the lectures and I got more interested in doing research. After a very interesting class about mammalian cells, I approached Prof. Dr Thomas Günther-Pomorski to ask him if he had a project for me in his lab. That simple question started an amazing scientific adventure.
Who are your role models in science? Why?
Actually, I grew up among researchers. Both my parents are university professors and I really admire them a lot. When I was a child, I travelled with them to conferences or when visiting their project colleagues around the world. Since I was a kid, I understood that research is not only done in an office, but that it is also important to be curious, to read, to talk with experts around the world, to travel and to be persistent. They both proved to me that you can be an amazing researcher while also being a good parent. They encouraged me to study abroad and helped me to gain a different perspective when I struggled with my PhD.
What's next for you?
Right now, I have a postdoc position at a small discovery-stage biotech company called Senolytic Therapeutics in Barcelona. Our aim is to develop novel medicines that target senescent cells in age-related diseases. It is a very interesting field and with a lot of potential. I decided to leave academia because I wanted to do more practical research and step into the pharmaceutical world. I felt that in a company, I could get closer to the people that require scientific help. I am looking forward to applying the research and the knowledge in finding solutions for different diseases or health problems.
Tell us something interesting about yourself that wouldn't be on your CV
I am a very creative person and I love art. I have been doing pottery since I was 10 years old and I have been sewing and doing crochet since I was fifteen. Since I was a teen, I have also been experimenting with photography. I use digital cameras but also old cameras like polaroid or 35 mm roll cameras. In recent years, I have started to love drawing and painting with aquarelles. When I was eighteen, I had difficulty choosing between a science degree or a more creative bachelor. I actually did two years of an advertising degree, but I really missed learning more about nature and the world we live in. Studying biology enlightened my life. Now, my free time is full of paint stains and notebooks with new crafting projects.
Marta Grifell-Junyent's contact details: Senolytic Therapeutics, Parc Científic de Barcelona, Carrer Baldiri Reixac 4-8, Barcelona 08028, Spain.
E-mail: [email protected]
