Congratulations to Marie Goret on the acceptance of her thesis!

Summary of Her Research Work
Mutations in DNM2, a key regulator of membrane trafficking, cause two neuromuscular diseases: centronuclear myopathy (CNM) and Charcot-Marie-Tooth neuropathy (CMT), which are thought to result from gain- and loss-of-function mechanisms, respectively.
While reducing DNM2 expression has been shown to improve phenotypes in CNM models, the pathophysiological mechanisms and therapeutic strategies for DNM2-related CMT remain largely unexplored.
Here, genetic modulation of DNM2 and its negative regulator BIN1 in a mouse model of Dnm2-CMT demonstrated that increasing DNM2 activity or reducing BIN1 significantly improved CMT features, thus revealing an opposite mechanism compared to CNM.
However, early or late AAV-mediated Dnm2 delivery, as well as tissue-specific expression designed to assess cell-autonomous mechanisms, did not provide therapeutic benefit and in some cases induced adverse effects.
These results highlight opposing mechanisms between DNM2-CNM and DNM2-CMT, provide the first proof of concept for DNM2 targeting in CMT, and underscore the challenges of clinical translation.

Skills Acquired at IGBMC
During my PhD, I learned to independently conduct a research project from start to finish, to organize and coordinate several projects simultaneously, and to supervise internship students.
I strengthened my technical expertise at the bench and my scientific knowledge through literature reviews, conferences, and seminars.
I also had the opportunity to investigate the pathological mechanisms of two diseases (CMT and CNM) in different tissues (peripheral nervous system and muscle), while testing various therapeutic approaches such as CRISPR-based genome editing and AAV-mediated gene therapy.
These projects helped me develop my ability to formulate hypotheses, collaborate with partners and service providers, write and publish scientific papers, and present my results at conferences.

Life at IGBMC
What I particularly appreciated at IGBMC was the stimulating scientific environment, characterized by the diversity of research topics and the richness of scientific exchange.
The numerous technological platforms available allowed me to broaden and diversify my experimental approaches.
Finally, the regular opportunities to present my results during seminars were both formative and highly motivating.

Collaboration
Patricio Aguirre-Pineda & Sylvie Friant
(Medical Genetics Laboratory, INSERM UMRS 1112, University of Strasbourg, CRBS)

Funding and Partners
GIE, AFM-Téléthon, and ANRs

Future Plans
After my PhD, I plan to apply for the forensic biology examination to join the scientific police.
In parallel, I remain open to postdoctoral or R&D positions in private laboratories to further develop my technical expertise and explore new research topics.