Published on 23.11.2020
Research Acceleration
- Portrait
The first thing that stands out when you meet the two young researchers is the happiness of having passed the entrance exam to Inserm. Because with the number of "competitors", the selection is drastic and the two researchers had to pass the competition several times: 3 times for Emilie Dambroise and 4 times for Benedetta Ruzzenente. While the first time I failed by a very small margin," recalls Benedetta Ruzzenente, "the next two times I didn't even pass the oral exam, so I didn't believe in it anymore ".
"To succeed, you need a sufficiently mature project", says Emilie Dambroise, who will now be able to devote herself more serenely to the research that has been close to her heart since her thesis, namely identifying the physiopathological mechanisms deregulated following the modification of the FGFR3 gene and responsible for craniosynostosis, diseases due to "premature welding" of the skull bones. This poor fusion of the cranial vault has repercussions on the development of the brain.
Craniosynostoses: a fish model for a better understanding
"The mutations in the gene (FGFR3) we are studying are responsible for either dwarfism or craniosynostosis", she describes. During my PhD in Laurence Legeai-Mallet's lab at Imagine, I characterized a mouse model of achondroplasia (which is the most common form of dwarfism) to study the function of this gene during the development of long bones. I then wanted to understand the role of FGFR3 during skull development, but it turned out that what we observed in mice was quite different from what we see in humans.
I therefore went to train during my post-doctoral studies on another model: the zebrafish whose mechanisms responsible for skull formation are close to those described in humans". Then, Emilie Dambroise returned to Imagine and developed a zebrafish model to study the mechanisms regulating skull formation, to understand the consequences of the mutation of this gene responsible for craniosynostosis, but also to identify ways to restore the defective mechanisms.
"With this model, which is better adapted than the mouse model, I will be able to test different therapeutic strategies", enthuses the young researcher.
Even if there is still a long way to go, I have in my possession a large number of tools to get there and this is surely what also seduced the jury for my entrance to Inserm
Mitochondria: a universe to explore
As for Benedetta Ruzzenente, she has been dedicated to the study of mitochondria since her PhD, defended in 2005 at the University of Padua in Italy. So why this interest in what are considered to be the cell's energy factories? "Because much remains to be discovered about these small organelle seats of the reactions that convert glucose into the energy molecule, ATP".
After working on the biology of mitochondria in Sweden and then in Germany, she joined Agnès Rôtig's team at the Imagine Institute in 2015 to study the pathological consequences caused by defects in the expression of mitochondrial genes. "These are very heterogeneous diseases involving more than 300 genes to date", she recalls. "They are also quite difficult to recognize since the clinical signs are often very similar to those observed in other diseases".
For the young researcher, being able to work on these pathologies represents a "golden mine" by offering unique opportunities to discover new mechanisms for regulating mitochondrial function, and the collaboration with the Reference Center for Mitochondrial Diseases from Child to Adult (CARAMMEL) at the Necker-Enfants malades Hospital is an asset for her research.
Among this projects is the study of the tissue specificity of diseases related to the mutation of a nuclear gene coding for a mitochondrial protein involved in the regulation of mitochondrial gene expression. "Although these genes are ubiquitous, mitochondrial pathologies most often affect only one organ," explains Benedetta Ruzzenente. "I am therefore trying to understand where this tissue specificity comes from using mouse models". Beyond these mechanistic approaches, the young researcher is also beginning to develop therapeutic approaches, notably based on gene therapy.
Two young researchers to follow!