Charlotte François, who obtained a permanent position in Bruno Hudry’s team last year, has a long-standing interest in scientific questions relating to the reproductive system and cell sexualization. She first took a Master’s degree in Reproduction and Development at Paris 7, with a gap year between the 1st and 2nd to perfect her English in Aberdeen, Scotland. Then she joined the lab of Joelle Cohen-Tannoudji in Paris 7 for her PhD, where she developed two projects in parallel. In the first one, she found that while estradiol had no effect on the proliferation of cells from a rare tumor of the ovary, Granulosa Cell Tumor, it decreased their migration through a non-classical signaling pathway involving ERK kinases. “For the second project, I worked on mouse mini-puberty, defined as a post-natal hormonal peak, with FSH and estradiol production, but no follicle growth and maturation, and no ovulation”, she explains. “This poorly-understood stage, which also occurs in many mammalian species including our own, is important to study as it is believed to play a role in sexualizing the brain”. In an effort to understand why elevated concentrations of FSH were unable to support follicle growth during this infantile period contrary to adult stage, Charlotte found that FSH could not induce cyclin D2, a major driver of granulosa cell proliferation but increase the expression of steroidogenic genes to sustain the production of estradiol. Her works thus revealed a decoupling in common regulatory pathways of FSH during the infantile period.

Then Charlotte thought for a while that she would go into the private science sector. One way of seeing things more clearly and gaining the necessary perspective for life choices is to go away for a while. For example, to a school in Antsirabe, Madagascar, to do humanitarian work.  “It was a rich but sometimes discouraging experience, given the limited resources available”, she admits. It was also at this time that a French start-up contacted Charlotte and offered her the chance to work on a promising project, in collaboration with a major Parisian cancer institute. “I learned a lot during this year and a half, about the specific needs of the private sector and about project design, but I also found out that it was not for me”, says Charlotte, who was eventually and once again attracted by fundamental scientific themes related to reproduction and cell sexual fates. This is how she was recruited as a post-doc in Bruno Hudry’s team.

Here at the iBV, Charlotte began work on an exciting project linking metabolism and spermatogenesis in the fly. At the time, several studies had revealed that metabolism is much more than a question of energy resource use and mitochondrial function. Certain metabolites, secreted by the cells that produce them, are capable of influencing the destiny and differentiation of other cell lineages. This may be of particular importance for the reproduction of organisms, as fertility is largely dependent on diet and environmental factors in general.

“Before I arrived in the lab, Bruno had shown that gut-derived citrate, a product from intestinal carbohydrate metabolism and found in the extracellular milieu, contributed to fly spermatogenesis. During my post-doc, I characterized the regulatory cascade leading from citrate transformation into acetyl-CoA, which causes in turn the N-terminal acetylation of proteins specifically involved in spermatid differentiation”. In this work, published in Nature Communications in 2023, Charlotte also found that N-terminal acetylation shields these key proteins from proteasomal degradation. “This means that acetyl-CoA does not only impact transcriptional programs through epigenetic modifications but also directly and quickly changes cellular proteome stability”. Charlotte’s findings, that define coupling mechanisms between the metabolic state of an organism and the dynamics of spermatogenesis, are especially important as they help to understand how fertility can quickly adapt to environmental changes. Finally, she found that this role of acetyl-CoA was male-specific, as functional disruption of the cascade in female gametes did not modify female fertility.

Since the beginning at the iBV, Charlotte has also been involved in passing on knowledge to the public, and in particular to young people, with the Déclics operation in high schools, and soon a participation to the “Cordées de la Réussite” at Drap’s high school, with Nathalie Billon.  At last, Charlotte has another major passion, outside science, and that is sport. A long history of running (including a 45-minute personal best on the iconic Prom Classic), endless swimming pool lengths and sunny Nice’s region naturally led her to the practice of triathlon, as a member of the famous Cavigal club in Nice. “I just need to really and seriously get on the bike this year!”

We wish Charlotte every success in research and sport!