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Pierre Léopold: “Why are my two arms the same length?”

To answer this deceptively simple question, Pierre Léopold, Inserm Research Director, head of a team at the Institute of Biology Valrose (Nice), has been awarded two successive grants by the European Research Council (ERC Advanced Grant).

How did your research project on growth come about?

Pierre Léopold © Inserm/P. Latron

I had, and continue to have, a passion for questions about the development of the body. I did my PhD at a time of major discoveries in embryogenesis related to the development of the body. I started working on Drosophila, the predominant model used to study these questions. At the University of California, where I did my post-doc, I tried to find out how cell proliferation is controlled by developmental signals. I then logically went from the question of how cells are organised within organs to the quantitative problem of growth, and the production of tissue mass. 

And you brought your questions back to France... 

Yes. After starting with funding from ATIP-Avenir, in 1998 my team found a favourable environment at the University of Nice. We first wanted to understand how the body adapts its growth to the amount of food available. Using genetic screening techniques, we identified the link between nutritional information and growth (orchestrated by the brain). It is the fat body, the insect equivalent of the adipose tissue and liver in vertebrates. 

Why apply for an ERC grant?

In 2010, it was the right time: we had opened up an area combining genetics and physiology, and published our results in the major journals. Substantial funding such as an ERC grant could give us complete autonomy for 5 years! I therefore wrote a proposal for a project called GroLeo, in two parts. One was to identify the molecular messengers that transmit information between the fat body and the brain. The other asked a new question based on old observations: if the growth of an organ is slowed by an injury or by genetic means, the development of the whole body slows for the time taken to repair it, to maintain consistency in the proportions of the future adult. In particular, metamorphosis – the equivalent of puberty and the time at which adult size is reached – is delayed. Hence a signal leaves the organ buds to modulate the triggering of metamorphosis by the brain. But what is this signal? 

What was the outcome?

Once the proposal was accepted, we acquired instruments, particularly an essential confocal microscope. I was able to recruit PhD students and post-doctoral fellows who did remarkable work. Result: we achieved all our goals! We found signals coming from the fat body in response to nutritional information. The signal that coordinates metamorphosis was also identified: it is a relaxin, encoded by the Dilp8 gene. With the resulting increased visibility of the team, I obtained a second ERC grant in 2015, for a project called Vitruvius. 

What is it about? 

Following GroLeo, it is aimed at identifying the mechanisms by which Dilp8 acts on the brain, and seeing how the signal travels back down to the peripheral organs. We then need to understand how the latter coordinate themselves: for example, why the two wings are the same length, which no longer happens when Dilp8 is absent. 

Do these mechanisms seem to translate to the vertebrates?

Yes, and that is the object of the third part of Vitruvius. We will transpose these questions onto the axolotl, a type of salamander used as a model for tissue regeneration. We already know that Dilp8 is a relaxin, a family of hormones conserved in vertebrates, some of which are potentially active in the stump of an amputated limb.

Find out more about Pierre Léopold and his work
Pierre Léopold directs a team, The Genetics and Physiology of Growth in Drosophila, at Inserm/CNRS/University of Nice Unit 1091, at the Institute of Biology Valrose (Nice). He received an Inserm Research Prize in 2011. 

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