Valérie Gabelica leads a team dedicated to the analysis of nucleic acids using mass spectrometry in the “Nucleic acids: Natural and artificial regulation” unit, in Bordeaux. The chemist was awarded an ERC Consolidator grant to develop a method aimed at uncovering nucleic acid folding mechanisms.
What is your scientific background?
A qualified chemist, I did my PhD thesis at Liège University, in mass spectrometry. It is an analytical tool that is used to very accurately measure the mass of molecules, with a view to deducing their composition.
As a user, I’ve been hampered by the limits of commercial instruments. It was this that first drove me to extend my research to include theoretical aspects and instrumentation, working closely with physicists.
In addition, I was already interested in nucleic acids as research topics: DNA and RNA, substances that carry genetic information. So I met biologists who discussed with me the questions they had concerning these molecules. Having completed my post-doctoral research, I returned to Liège to see how we could use mass spectrometry to address these questions.
Why nucleic acids?
Mass spectrometry focusing on biological macromolecules was being developed for sequencing purposes. Where nucleic acids were concerned, it was soon abandoned to make way for other methods. However, despite the fact that it had become “unfashionable”, my interest continued, but from another viewpoint: I wanted to know how nucleic acids combine to form complexes and bind to ions or small molecules, potentially of interest to the pharmaceutical sector. Our research led to the discovery of unexpected complexes on more than one occasion!
How did you come to join Inserm in Bordeaux?
It was the unique configuration of the scientific environment in Bordeaux that prompted my decision to leave Belgium. My team is based in the European Institute of chemistry and biology (IECB), a project incubator bringing together teams from a variety of backgrounds: chemists, biologists, engineers, etc. Previously, I was working on nucleic acids in a chemistry department. Here, I’ve joined a lab working on these same molecules and I’m contributing my expertise in the field of physicochemistry.
I came to Bordeaux in January 2013 thanks to Atip-Avenir funding and I immediately wrote the research project that enabled me to get the ERC grant because I knew what I wanted to do! The ERC funding allowed me to purchase extremely expensive equipment and recruit PhD students, engineers and post-doctoral researchers.
What does the project entail and how much progress have you made?
The aim is to find out more about the spatial conformation of nucleic acid complexes detectable using mass spectrometry. To do so, it is necessary to develop the instrumentation. One commercially available technique - ion mobility spectrometry - separates molecules injected into the system on the basis of their displacement in an electric field. We’ve already made considerable progress in interpreting these data in terms of spatial structure.
We’re also developing a technique that doesn’t exist in either the market or the literature, which consists in “probing” nucleic acid structures with a laser, everything taking place in the mass spectrometer. We’ve acquired the necessary equipment and assembled it. The task now is to take measurements to prove whether we have been successful. Lastly, we have to apply all of this to nucleic acid complexes of interest to biologists.
So are you a biologist now?
No, I'm a physical and analytical chemist: that’s my core business; it’s what I do, every day. I want to focus on the fundamentals and continue to push back the boundaries in terms of instrumentation. My philosophy is to provide the community - biologists, for example - with the techniques developed, and that is what Inserm and the IECB allow me to do.
Find out more about Valérie Gabelica and her research
Valérie Gabelica leads the Mass spectrometry of nucleic acids and supramolecular complexes team within Inserm/CNRS/Bordeaux University unit 1212 (Nucleic acids: Natural and artificial regulation (ARNA) unit)