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Prof. Philippe Sansonetti: Winner of the 2012 Grand Prix Inserm

Philippe Sansonetti
p. 22

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Source: La lettre, no. 35, December 2012

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1I would like to address special thanks to my colleagues. Throughout all these years, they have made the Microbial Molecular Pathogenesis Unit what it is, and I dedicate this INSERM prize to them.

2Junior researchers’ careers are particularly important to me. Their role in society lacks recognition – and remuneration –, yet they show exemplary qualities: passion, curiosity, rigour, honesty, critical thinking, selflessness, universality and modernity, and trust in the future, for science is no short-term affair. Education and research are the only real guarantors of our future.

3I would also like to thank microbiology and say a few words about it; more precisely about the human-microbe interface which corresponds to the INSERM. More than ever, micro­biology is a crucial model in fundamental biology and its capacity to interface with other disciplines: cellular biology, immunology, and now the biology of development. These interfaces have seen the emergence of many recent discoveries, as they have their full role to play. As Theodosius Dobzansky said, “nothing in biology makes sense except in the light of evolution”. As multicellular eukaryotes, we are born from bacteria and have evolved with them. All the phyla, from protozoa to higher mammals, host a microbiota. In light of co-evolution, the maintenance of these floras makes sense. Symbiosis models­ in primitive organisms attest to this and there is little risk in thinking that what holds true for calamari, flies or earth worms also does for humans.

4Recent research has shown the crucial role of the microbiota in nutrition and the maturing of the immune system of mice. Yet who would have thought it was involved in the late stages of the brain’s maturing, or as we have just shown in our laboratory, in the protection of adult stem cells ensuring the regeneration of my favourite epithelium, the most noble of all, the intestinal epithelium?

5A new page of microbiology is being turned which is going to reveal the breadth and depth of this symbiosis, which makes us a eukaryote-prokaryote hybrid. This is also a new page of medicine, for the dysfunctions of the homeostatis of this symbiosis seem to hold the etiology of diverse diseases: insulin resistance, obesity, diabetes, inflammatory bowel diseases, allergy/atopy, or even certain colon cancers. These all provide new interface opportunities for microbiological research.

6We are also looking at pathogenic microbes, in these times of infectious emergence. While they form a tiny minority next to microbiota, it is nevertheless an active one.

7As I rewrite War and Peace, I am trying to draw a bridge between symbiosis and pathogenecity, but on the mucosal surfaces, in order to understand better how our immune system differentiates between pathogens and symbionts. How does the host sense the microbial danger and adjust its response accordingly? This has a corollary: pathogens’ manipulation of this perception of danger and of the immune response through molecular strategies which we are deciphering and that never stop amazing us.

8Shigella is a superb study model, due to the range of effectors devoted to the subversion of the host’s defences that it expresses to invade the digestive tract. Recent examples of such strategies which my group has revealed include: blocking­ the secretion of ATP, a major danger signal, by closing the connexin hemichannels of the infected epithelial cells; post-translational modifications of the inflammatory response channels’ key proteins, both in the cytoplasm and in the nucleus, by taking control of the regulation of pro-inflammatory genes on the transcriptional and epigenetic level; immobilization of the T lymphocytes travelling towards the T zone of the lymph nodes.

9Pathogens know us perfectly well, especially our immune system. In fact, better than we do. Let us therefore let them educate us, through the analysis of their subversive strategies. Let us use knowledge of these strategies to develop new treatments, new vaccines. That is what we are currently doing, faithful in this way to the Pasteurian tradition.

10I would like to conclude by thanking my friends and my family gathered here today, my mother, my brother, my children, my wife Nicole, and particularly by reassuring them that in spite of appearances, I do love them more than microbes.

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Philippe Sansonetti, « Prof. Philippe Sansonetti: Winner of the 2012 Grand Prix Inserm  », La lettre du Collège de France [En ligne], 7 | 2015, mis en ligne le 29 octobre 2015, consulté le 23 mai 2017. URL : http://lettre-cdf.revues.org/2598

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Philippe Sansonetti

Microbiology and Infectious Diseases

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