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. Marielle Saclier is first author on ‘ Interplay between myofibers and pro-inflammatory macrophages controls muscle damage in mdx mice’, published in JCS. Marielle conducted the research described in this article while a PhD student in Bénédicte Chazaud's lab at the Institut Cochin, Paris, France. She subsequently joined the lab of Graziella Messina at the University of Milan, Italy, as a postdoc to investigate the interaction of macrophages with the cellular environment during muscle regeneration, both as a model of sterile inflammation and in the context of diseases such as muscular dystrophy.
How would you explain the main findings of your paper in lay terms?
Macrophages are immune cells that not only eat dead cells and clean the body but also participate in tissue homeostasis. After muscle injury, macrophages push muscle stem cells to proliferate and then differentiate to re-form muscle. Unfortunately, in genetic dystrophic diseases, information sent by macrophages is misregulated and contributes to muscle loss and progression of the disease. We observed that dystrophic muscle fibers themselves participate in the misregulation of macrophages and push them toward a pro-inflammatory phenotype. We found that NaHS (an H2S donor) reverses macrophages from a pro-inflammatory phenotype to an anti-inflammatory phenotype, which in turn rescues dystrophic muscle by decreasing fibrosis and areas of muscle damage. Our work demonstrates that modulating macrophage phenotype can protect dystrophic muscle and could provide another perspective on the treatment of muscle diseases.
Were there any specific challenges associated with this project? If so, how did you overcome them?
We performed co-culture experiments using several cell types. In this type of experiment, the challenge is to find the right balance between the numbers of one cell type (e.g. macrophages) and another (e.g. muscle fibers or muscle stem cells), as exists in the entire body. Moreover, cells need serum to live, and so culturing cells with low serum concentrations causes them to suffer and die, while high serum concentrations can obscure the effect of cellular secreted factors and cellular interactions.
When doing the research, did you have a particular result or ‘eureka’ moment that has stuck with you?
We previously demonstrated that pro-inflammatory macrophages have a negative effect on dystrophic muscle, so we logically decided to push macrophages toward an anti-inflammatory phenotype. I was not expecting such a rescue with anti-inflammatory treatment – it was really exciting to observe that our hypothesis was correct!
Why did you choose Journal of Cell Science for your paper?
This research is about cellular interactions between different cell types and how the modification of the phenotype of one cell type can improve the disease context. Thus, Journal of Cell Science is perfectly adapted to our research, and that's why it was our first choice for this work.
Have you had any significant mentors who have helped you beyond supervision in the lab? How was their guidance special?
This work started when I was a PhD student in the lab of Bénédicte Chazaud. She was always present to drive us forward while doing our research. She discussed technical issues and scientific ideas, and importantly, she let us develop ideas and test new hypotheses.
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 was always fascinated by how perfectly the body functions. How is it possible that all these different cells are working together? And how can one little modification sometimes induce such dysregulation? Cells always talk to one another, even when all is fine in the body. Thus, understanding what happens when all is functioning well is necessary to understand what goes wrong during disease. Moreover, the excitement of scientific results (which could be the validation of a hypothesis, or the opposite) is something really special and priceless!
Who are your role models in science? Why?
I really admire female scientists who for centuries had difficulty finding a place in research and struggled to see their works recognized as their own. They still pursued what they loved doing and did not lose their motivation.
What's next for you?
My plan is to gain an academic position as a research associate.
Tell us something interesting about yourself that wouldn't be on your CV
I love to hike in mountains and forests – this is really relaxing. And sometimes it's nice to just sit and read a book with some homemade biscuits and a hot cup of tea.