Dear Cell (transcriptions)

Perception of Self and Nonself in Life

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Dear Cell (transcriptions)
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Perception of Self and Nonself in Life is a project by Regina Hübner, realized with the collaboration of CIML Center of Immonology Marseille-Luminy and of Inmed Institute of Mediterranean Neurobiology, at IMéRA - Institut d'études avancées d'Aix-Marseille Université, in 2019 in Marseille.  The visual part of the project is entitled Dear Cell and it is composed by the videos Dear Cell (eyes), Dear Cell (letters), Dear Cell (transcriptions) and Dear Cell (cells).  

 

17 Research Directors, Group Leaders, Professors and Researchers of CIML and Inmed are the Protagonists of Dear Cell.

They wrote a letter to their object of research and another letter to themselves, personifying their object of research.

They provided the images of their objects of research. They showed their eyes.  

 

 

Transcriptions of the letters from ME-researcher to you-object and the letters from YOU-object to me-researcher by the Protagonists

 

       Jean Pierre Gorvel, Research Director, Group Leader, CIML

Research on Host Pathogen Interaction 

       Philippe Pierre, Research Director, Group Leader and Director CIML

   Research on Dendritic Cells and Pathogens Sensing 

       Philippe Naquet, Professor, Group Leader, CIML

Research on Immunology

       Pierre Milpied, Chargé de recherche, Group Leader, CIML

Research on Integrative B Cell Immunology

       Sandrine Roulland, Research Director, Group Leader, CIML

Research on Cancer Biology 

       Didier Marguet, Research Director, Group Leader, CIML

Research on Membrane Dynamics and T Lymphocyte Signaling 

       Agnés Baude, Senior Scientist, Inmed

Research on Neuroscience 

       Marc Dalod, Research Director, Group Leader, CIML

Research on Type 1 Conventional Dendritic Cell 

       Dario Armando Leone, Researcher, CIML

Research on Endolysosomal Trafficking in Immune Cells 

       Sandrine Sarrazin, Researcher, CIML

Research on Stem Cell and Macrophage Biology 

       Serge Van De Pavert, Research Director, Group Leader, CIML

   Research on Development of the Immune System 

       Mauro Gaya, Chargé de recherche, Group Leader, CIML

Research on B-Cell Immunology to Infection 

       Françoise Muscatelli, Research Director, Group Leader, Inmed

Research on Function of the Brain during Development 

       Sophie Ugolini, Research Director, Group Leader, CIML

Research on Neuro-Immunology 

        Michael Sieweke, Research Director, Group Leader CIML, Humboldt Professor

Research on Stem Cell and Macrophage Biology 

          Bertrand Nadel, Research Director, Group Leader, CIML

   Research on Genomic Instability and Human Hemopathies 

 

 

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JEAN-PIERRE GORVEL

Research Director, Group Leader, CIML

Research on Host Pathogen Interaction

 

Jean-Pierre Gorvel

Letter from ME-researcher to you-object (Brucella and other bacteria)

13 June 2019

 

Dear Brucella and other bacteria,

We have come a long way you and I. I came from a pure cell biology background and you permitted me to draw a bridge between basic and biomedical research. Instead of studying inert beads, you led me into the complicated war between a pathogen and its host. On the other hand, you, the beneficial bacteria, like the microbiota, blur the division between self and nonself.

 

I now realize how much nonself we are. Indeed, depending on the scale, we are much more nonself than self. Therefore, the idea of self from a microbiological point of view is clearly an illusion. How much of a self can we consider ourselves when microorganisms outnumber human cells ten to one? We are increasingly aware of the pivotal role these microorganisms perform in human health for good or for ill.

 

On the other hand, during an infection, the sense of self is heightened because it results in a war between the organism: in this case the human being, i.e. me and you, the pathogen.

 

Brucella, you are such a worthy and ancient opponent. The relationship between your species and mine is extremely old. You are related, in evolutionary terms, to one of the most outstanding acts of symbiosis, the mitochondria.

 

Virulence decreases as the time of the relationship between the host and the pathogen increases. You come into our bodies, practically unannounced. You fool our immune system. You are incredibly difficult to diagnose as, in the acute stage of the infection, you can disguise yourself as a common cold. You can stay in our bodies for years, and only in the long term, you will camouflage yourself again as arthritis. Your capacity to confound our defences is outstanding. Such capacity has been the focus of study and research for many years of my life. In addition, it is still not resolved. You will continue to surprise me.

 

As to the microbiota, you might turn out to be the real captain of our bodies. In this case, the lines of the self are blurred. How much self-will can we pretend to have if you are the ones who are in charge of our well-being? You can control one of the most human characteristics: our moods. If the balance between the trillions of microorganisms and the cells in our bodies is attained, we can thrive with this perfect symbiosis and we can aspire to become a united self within this cellular and microbial community.

 

 

Jean-Pierre Gorvel

Letter from YOU-object (Brucella) to me-researcher

13 June 2019

 

Dear JP,

I am not sure if I like you. In fact, I think not. You have spent your time trying to decipher the mechanisms in which I, Brucella, can fool the immune system of your species. It is a very ancient battle, I would even call it a war, and to be honest, I am not sure you will win this one… I am very conscious of my self and of your self, you, a host in which I could live for as long as you live, provided that you do not diagnose me and treat me with vaccines (in the case of animals) or with antibiotics (in your case).

 

I have had a very long time to perfect my weapons. The first one is to invade your organism without causing too much alarm. I am able to withstand a huge loss at the beginning of infection making you believe you are winning. I will infect a few cells (macrophages) which will be enough to keep on living for many years in your organism. I am even able to hijack your own cells (neutrophils) as a Trojan horse to disseminate myself in your body. In summary, I am the bee’s knees.

 

At the beginning of the infection, you will think it is a common cold or, in the worst case a flu, both caused by viruses and you will therefore not think of attacking me with antibiotics. Many years later, I will live in your body and you will get confused again thinking that you have arthritis, and again, fail to treat me with antibiotics. In many cases, I will live for a very long time and die with you.

 

I am able to cause havoc in your livestock as well: cattle, pigs, sheep and goats. However, if you think you are safe because in 40 years you will all be vegans, think again. I am able to infect wildlife as well: camels, boars, deer, voles, frogs, worms and even your beloved dogs and dolphins.

You have spent a long time studying my weapons and me. You have made good progress and I salute you for trying. At least you have deciphered my mechanism of entry, how I am able to withstand big losses at the beginning, the cell in which I can multiply while hiding, the blurred messages I am sending to your immune system to keep concealed for many years. In addition, you have an excellent candidate for a vaccine for cattle and sheep. You have won many battles but your war is lost. My capacity for hiding will continue to surprise you. The ways in which I can pass blurred signals to your immune system will still confound you.

 

 

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PHILIPPE PIERRE

Research Director, Group Leader, Director CIML

Research on Dendritic Cells and Pathogens Sensing

 

 

 

Philippe Pierre

Letter from ME-researcher to you-object (Dendritic Cells and Innate Immunity)

22 June 2019

 

Ma vie se confond avec l’objet de ma recherche. Méandres des sentiments humains, où, magie de l’inconnu, volonté de comprendre, et imagination, se rencontrent pour contribuer à ma personnalité. Obsession de comprendre l’inexploré, de résoudre les puzzles de la vie, en décortiquant les cellules à l’envi, en donnant aux molécules des attitudes humaines et en reconstruisant des histoires biochimiques à la façon des romans d’aventures.

 

Te choisir, toi, l’immunité, dans toute sa complexité refoulée, comme sujet de mes interrogations, était probablement un choix narcissique. L’idée même de te comprendre pour rendre la vie des autres moins douloureuse et moins dure face à la maladie est un choix égoïste et arrogant ! Comment penser pouvoir faire seul la différence face à la complexité incommensurable de l’organisation de ta vie ? Poussé par cette envie tellement humaine d’aller là où nul n’est déjà parvenu, je ne peux résister à essayer de te comprendre, comment toi, cellule du système immunitaire, t’organises-tu pour résoudre tant de problèmes et parvenir à tes fins en organisant des actions d’éclats et préserver ton hôte des attaques incessantes de l’autre ?  Comment arrives-tu à distinguer les marques de la sécurité de celles du danger ? Le soi de l’autre, quand leurs différences sont si ténues ?

Ton savoir est tellement ancestral, je suis tellement béotien ! Certes mon attitude, bien que bienveillante, est souvent destructrice à ton égard. Te détruire pour mieux te comprendre, c’est dans la logique de l’approche scientifique, une sorte de psycho-analyse biochimique de tes changements et de tes comportements face à l’adversité de ton environnement. Parfois, tu t’égares et deviens une menace pour ton hôte que tu as juré de protéger. En dépassant tes attributions, tu propulses le système entier dans le chaos et l’autodestruction, pourquoi ta perfection devient-elle si imparfaite ? Ma quête sera-elle donc sans fin ? Probablement ! Mais j’ai compris que cette obsession m’a finalement permis de te comprendre plus intimement, oh, peut-être pas complètement mais suffisamment pour pouvoir t’apprivoiser. Mais grâce à toi, surtout j’ai pu rencontrer d’autres humains ayant la même envie de partager l’aventure et la découverte de la perfection imparfaite, je ne suis plus seul !

 

 

 

Philippe Pierre

Letter from YOU-object (Dendritic Cells and Innate Immunity) to

me-researcher

22 June 2019

 

Dear Researcher,

Many times, I have wondered what was my mission and fate, the origin of my existence and my purpose in life, or was I life itself? Clearly to become the subject of your interrogations, I had to be special! The way I form, I react and carry what seems to be a purpose is clearly of interest for you, but to me! It is simply what should be done without emotions or thoughts.

 

I just obey to my program, integrated deeply in the matrix of other programs that together achieve what you call the host physiology and immunity. You have revealed, that I am multifunctional and spend my time giving instructions to maintain the integrity of the host, I am currently writing from. Indeed, you see me as a conductor, as a General, commanding to multiple fellow cellular effectors, instructing their programs, changing the behaviors of these would be soldiers to canalize their natural aggressiveness, towards the right kind of external enemies and obviously not against my host. My evolution has been long, I know how to adapt, to evolve, to carry my mission in complex and ever changing environments, to make sure that you, my host, lasted as a specie. Of course in the long run, I can make individual mistakes leading to collateral damage and individual drama, that despite what you think, should be disregarded, because I work for your collectivity, not for you as an individual. My task is harder than you think, it is so difficult to distinguish between the enemies and the host, they look so much alike, most of the time I succeed, but sometimes not, this despite my millenarian expertise. From angel, I can then turn into demon, and unleash my wrath to kill indiscriminately, slowly ordering the destruction of my host, instead of its enemies, further creating distress and incomprehension in your eyes. You try to forget that you are also an host and that you indirectly became the object of your own research by investigating me. You, with your simplistic ideas and reductionist views, always missing the big picture of my integration in a larger matrix program. If you want to pierce my deepest secrets, this is where you should start, by forgetting your individuality. You will start to see me as a global entity, I am not human and have no purpose, the survival of my host specie is my priority across the times, and individuality is not my concern.

 

 

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PHILIPPE NAQUET

Professor, Group Leader, CIML

Research on Immunology

 

 

 

Philippe Naquet

Letter from ME-researcher to you-object (The elusive Vanin)

1 July 2019

 

Strange and elusive object you were, a true conundrum. It took us almost 20 years to identify your intimate nature that was in fact written in your birth history but invisible to our eyes. You took us along unknown trails, shortcuts or endless zigzags, always hiding your identity to us. On this uncertain path, it took a few years to realize that you belong to the response to stress. We, as immunologists, were taught that the immune system can discern self from altered self, yet the nature of these alterations have remained quite out of focus for many years. And you were beyond the obvious answers; we sometimes thought that we had quit the trail of immunology to see the problem from another viewpoint. At least some of our colleagues thought so. But we persisted and believed in the rationale of our exploration. Progressively, clouds cleared up here and there. Indeed, your absence in mice influenced so many (too many?) modalities of immune responses. Your history as a protein shouted that you came from the confusing world of metabolism. We had to embark towards new worlds to decipher your contribution to the alteration of self, learn new techniques, meet new scientists from other scientific backgrounds. Their welcome was polite but we were strangers to them and again, arguing in favour of your potential interest required a dedicated and significant effort. A first light started to shine when we found that your expression in some tumours drastically changed their outcome in mice and funnily also in patients. We found ourselves hunting down a crowded path, for a novel regulation of a process that had been discovered a century ago and had been a highly motivating area of research for so many scientists over the world. And suddenly, we could position you in this new frame. You changed the ability of a cell to adapt its metabolism to stress. Not only that, this concept of plasticity could apply to non-tumor cells and ultimately to immune cells. The gap starts to vanish and what was a concept progressively became part of reality. Indeed, stress is a costly metabolic process also in the life of cells and our immune cells knew that much before us.

 

 

 

Philippe Naquet

Letter from YOU-object (a molecule for self-resilience) to

me-researcher

1 July 2019

 

Dear scientist, sorry to have been a burden to your team. As you may remember, my first discoverer Silvestro was a very charming Italian scientist. He named me without knowing me. I was a process for him, a groundless process on a garbage pathway and everything was fine. Then I was forgotten for almost a decade. Thank’s to you! you saw me from another angle although you did not know what was the real story. In fact it was like a new birth and I am happy to say that I was fully responsible for your encounter with Silvestro with whom, as I heard, you got along well. The problem is that suddenly I had two unrelated names, I had two identities and each one totally ignored the other one. Silvestro was a bit frustrated about that and created a chimeric name between the two. You also discovered my little brothers. I know that in order to reconcile everybody, you had to generate a living mouse in which I had totally disappeared as by magic. And yet, this mouse was perfectly alive to your despair. I have been responsible for much suffering in hundreds of mice but what is reassuring was to realize that I participate to mouse comfort and repair. I am a molecule for true self-resilience. That’s fun! Don’t abandon me too early, I still have a few things to teach you, trust me! Keep fighting!

 

 

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PIERRE MILPIED

Chargé de recherche, Group Leader, CIML

Research on Integrative B Cell Immunology

 

 

 

Pierre Milpied

Letter from ME-researcher to you-object (a/the Germinal Center)

2 July 2019

 

Dear germinal center,

I love you. I have loved you from the day I met you, even before that, from the day I learnt about your existence. You are such a fascinating object. I love your shape, I love your dynamics, I love your purpose and determination, I love your mess and uncertainty. I love your transience, your essence and your diversity. There are so many of you yet you all share the same essence, you all carry the same evolution.

I would like to get to know you better, but so far I have been intimidated and shy. For now, I watch you, focusing my molecular lenses on all cells that you harbour and that together make you. It has been enough to satisfy my obsession and get to know you. I know I am not the only person obsessed by you. I am not the jealous type, I like seeing others love you too and expose you in poses that I had not seen through my eyes. You are always beautiful. But maybe in the future I will want more from you. Maybe talk to you, tease you a little, or push you in directions you do not want to go to see how you react.

How did you become so perfect? How will you be in thousands, millions of years? I wish I could see through your past and future evolutions. As much as I am frustrated by my own limitations, I live in the peaceful hope that the next generations, my children and their progeny, will get to know you and love you even more than I do.

Yours sincerely,

Pierre

 

 

 

Pierre Milpied

Letter from YOU-object (a/the Germinal Center) to me-researcher

2 July 2019

 

Dear Pierre,

I love it that you love me. But I am wondering: do you really love me as a biological object? Or do you love the concept of me? The essence of what I do? It seems to me that by watching me, or should I say us since you are observing many of us, you try to understand our commonalities, not our singularities.

You scientists aim for the absolute model, the one equation that governs our behaviour as if there was only one germinal center. Do not forget that what makes us fascinating is our uniqueness, our adaptability, our history, our evolution. In your models, leave enough room for us to move and express our singularities. Look at us as a complex ecosystem of cities. Our inhabitants have stereotyped behaviors but they are all unique. Our streets are paved with the same asphalt but our maps are different. Our number and our complexity is our strength. Don’t you think evolution would have kept us simpler otherwise?

Keep that in mind, and keep watching us, we love it too!

All the best,

G.C.

 

 

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SANDRINE ROULLAND

Research Director, Group Leader, CIML

Research on Cancer Biology

 

 

 

Sandrine Roulland

Letter from ME-researcher to you-object (Lymphoma Cells)

9 July 2019

 

Dear lymphoma cells

 

First time I speak to you directly. I have the impression that you have been part of my life for a while now. We met for the first time more than 20 years ago. At that time, you were just a naive and inoffensive cell travelling around waiting for a signal to get waked-up but suddenly something happens! A break, a failure inside your milieu interieur and your destiny get changed for the rest of your life.

 

From now on, YOU will last forever in the body hidden in obscure niches, circulating within organs waiting to be reactivated, accumulating DNA alterations, growing but still latent and insidious. This situation can persist for a lifetime and will certainly never progress but we have no clues on that and this Epée de Damocles is not acceptable. You are no more part of the SELF. You are not either NON-SELF as you arise from an endogenous part of the immune system. You are an ALTERED SELF that the immune system will have to fight against.

 

For years now, I try to run after you in order to catch you, to understand who you are, where you go, how you communicate with your environment and what you plan to become in the future. I’m fascinating by such a long natural history that makes my day for years now. I wish to thank you for the pleasure you give me to motivate me every day to work deeply on you. Sometimes, I hate you for staying almost permanently in a small part of my brain but this is certainly what we call a passion.

BUT MY HOPE is that one day, I will succeed to capture you and your neighbours, to dissect the deepest I can and finally kill you!

 

If one day, my research saves a Human being life, it will be my victory!

 

Best Regards,

Me – lymphoma researcher

 

 

 

Sandrine Roulland

Letter from YOU-object (B-Cell) to me-researcher

19 September 2019

 

B this is not simply the second letter of the alphabet. I’m also a Cell, a B lymphocyte not to say the BETTER lymphocyte. It’s a bit pretentious but people are used to say that B cells are Boring, which I think is not true!

 

You have been working on me not for what I’m the best (protecting the host) but for what I’m Bad. I’m one of the most tolerant cell with an extraordinary capacity to proliferate, mutate my genome and tolerate these genomic changes to improve my functions.

 

But this has a cost, I can also acquire and tolerate deleterious breaks and mutations, become a transformed cell, stay silent for years in your body and then suddenly cause disease.

 

One single message for you Sandrine: You need to pursue your work and your attempt to fight me to keep people alive.

 

 

 

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DIDIER MARGUET

Research Director, Group Leader, CIML

Research on Membrane Dynamics and T Lymphocyte Signaling

 

 

 

Didier Marguet

Letter from ME-researcher to you-object (The Cell Membrane)

3 September 2019

 

« On a toujours cherché des explications quand c'était des représentations qu'on pouvait seulement essayer d'inventer. »

Paul Valéry, Cahiers, 1933

 

Comme le trait sur la feuille de papier, tu sépares deux mondes, frontière entre le dedans et le dehors. Et pourtant plastique, fluide, solide et liquide à la fois, tu modèles les êtres vivants tout en épousant l’édifice qui t’abrite.

Je ne peux te réduire à ce trait, je veux t’appréhender dans ta complexité, imaginer les mots pour te décrire, t’expliquer et te penser.

Te voir.

Tout reste affaire d’interactions électives, de répulsions, de cohésions et de coopérations. Alors, il me faut réinventer une « camera obscura » pour te figurer dans une image qui restera cependant sans relief. Il me faut sans cesse perfectionner l’outil pour espérer te dévoiler un peu plus, un peu mieux. Il me faut convoquer aussi de nouvelles épistémès pour imaginer l’espace-temps dans lequel tu évolues, mieux saisir les vibrations qui se coordonnent ou s’annihilent, te rendent malléable à tout instant, vivante.

Chemin faisant, avec ceux qui m’ont rejoint et m’accompagnent encore dans l’aventure, en se prenant au jeu des amis devenus, il nous faut expérimenter et comprendre, comprendre et expérimenter, et sans relâche toujours recommencer pour mieux t’imaginer. 

Tu es si simple et pourtant si complexe à saisir. Paraphrasant Edgar Morin dans la Méthode, par ta complexité, tu n’ordonnes pas mais tu organises, tu ne manipules pas mais tu transmets, tu ne diriges pas mais tu amènes à la vie.

Aujourd’hui encore, tu restes insaisissable, tu m’enchantes et me désespères.

Fascination.

 

 

English translation

Didier Marguet

Letter from ME-researcher to you-object (The Cell Membrane)

3 September 2019

 

« On a toujours cherché des explications quand c'était des représentations qu'on pouvait seulement essayer d'inventer. »

Paul Valéry, Cahiers, 1933

 

Like the line on a sheet of paper, you separate two worlds, boundary between inside and outside. And yet plastic, fluid, solid and liquid at the same time, you model the living creatures while embracing the edifice that houses you.

I cannot reduce you to this line, I want to capture you in your complexity, imagine the words to describe you, explain you and think about you.

To see you.

Everything remains a matter of elective interactions, repulsions, cohesions and cooperation. So, I have to reinvent a "camera obscura" to portray you in a picture that will however remain without relief. I must constantly improve the tool to expect revealing you a little more, a little better. I must also convoke new epistemes to imagine the space-time in which you evolve, to better grasp the vibrations that coordinate or annihilate each other, making you malleable all the time, alive.

Along the way, with those who have joined me and are still accompanying me in this adventure, by being caught up in the game friends became, we must experiment and understand, understand and experiment, and relentlessly reiterate this again.

You are so simple and yet so complex to grasp. Paraphrasing Edgar Morin in the Method, by your complexity, you do not order but you organize, you do not manipulate but you transmit, you do not direct but you bring to life.

Even today, you remain elusive, you enchant me and despair me.

Fascination.

 

 

 

Didier Marguet

Letter from YOU-object (The Cell Membrane steaking of the molecules that make it) to me-researcher

3 September 2019

 

“A violent order is disorder; and a great disorder is an order. These two things are one.”

Wallace Stevens, Connoisseur of Chaos, 1942

 

Dans l’obscurité de la nuit. Je suis l’unité, riche des multitudes et des diversités qui me font. Aujourd’hui, quelques-unes d’entre elles, pour l’occasion, revêtues de strass et paillettes, attendent pour briller, pour t’offrir dans l’instant la vision d’un désordre apparent, fruit de leurs gesticulations incessantes.

Pour toi.

Sous tes faisceaux de lumière.

Telles les sirènes émergeant du chaos de la nuit.

Feux d’artifice, tournoiement, transe, ou bien carole, branle, tarentelle, mime ou pantomime, que sais-je encore ? Amour et désamour, faisant et défaisant continument les liens qui les unissent, elles t’offrent au travers de ta « camera obscura » de baroques et insouciants spectacles, complexes et singuliers. Oui, ensemble, gouvernées par d’antinomiques liens, molle matière elles se déclarent, pour mieux s’apprêter entre elles, rester unies. Pour le meilleur et pour le pire.

A toi, maintenant de décrypter leurs ballets incessants. Pour t’aider, ou te désorienter un peu plus, elles ne se dévoileront certes pas toutes au même instant. Interroger chacune qui me compose, les unes et puis les autres, les unes et les autres en même temps. De-ci, de-là.

Alors, patiemment, il te faudra saisir chaque mouvement, le décomposer pour mieux le reconstruire et révéler les lois qui forgent mon tout, actif et communicant, s’accommodant la vie durant à mes sœurs circonvoisines.

Pour que le mystère s’accomplisse – VIVRE –.

 

La lumière les efface. Dans l’obscurité de la nuit, elles retourneront.

Poussières d’étoiles, pour l’éternité…

 

 

English translation

Didier Marguet

Letter from YOU-object (The Cell Membrane steaking of the molecules that make it) to me-researcher

3 September 2019

 

“A violent order is disorder; and a great disorder is an order. These two things are one.”

Wallace Stevens, Connoisseur of Chaos, 1942

 

In the darkness of the night. I am the unity, rich in the multitudes and diversities that make me. Today, some of them, for the occasion, dresses with rhinestones and sequins, are waiting to shine, to offer you in the moment the vision of an apparent disorder, the fruit of their incessant gestures.

For you.

Under your beams of light.

Like the mermaids emerging from the chaos of the night.

Fireworks, whirl, trance, or carole, branle, tarantella, mime or pantomime, who knows what? Amour and desamour, strengthening and weakening unceasingly the ties that unite them, they offer you through your "camera obscura", baroque and insouciant spectacles, complex and singular. Yes, together, governed by antinomic ties, soft matter they declare themselves, in order to better get on with each other, to remain united. For better or for worse.

Now, you have to decrypt their incessant ballets. To help you, or to disorient you a little more, they will certainly not reveal themselves all at the same time. To interrogate each one who makes me, some and then the others, ones and the others at the same time. Here and then.

Then, patiently, you will have to grasp each movement, break it down to better rebuild it and unravel the laws that forge the all, active and interconnected, to accommodate my fellow sisters throughout our life.

For the mystery to be accomplished – been alive -.

 

The light turns them off. In the darkness of the night, they return.

Stardust, forever…

 

 

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AGNÉS BAUDE

Senior Scientist, Inmed

Research on Neuroscience

 

 

 

Agnés Baude

Letter from ME-researcher to you-object (The Neurons)

10 September 2019

 

Thanks Ramon y Cajal to have given me the taste to wander in the neuronal forest. Each time I go to the microscope, it is similar to when I walk in a forest.

In the forest, my eyes follow the giant trees with their huge trunk, their roots, their branches and their leaves. Under my microscope, when I observe pyramidal cells in the neocortex, I also follow their trunk, their basal dendrites their apical dendrites and their spines.

Suddenly, a bird leaves a branch and flies away. I follow it, but I end up losing it. I have forgotten my binoculars.

Suddenly, something arouses my curiosity. An axon comes off and goes away. I have my microscope and I can follow it all along his way through the depth of the brain.

In the jungle of the brain, you can observe new types of cell with different roots, branches or leaves, new species. When, because of neurological diseases, epilepsy or trauma, your jungle is in fire you can lose some cells, some species. It is the same when the amazonian or the siberian forests are in fire, we lost trees and animal species.

When I observe you, small neurons, through my microscope, when I observe you, giant trees, my only conclusion is that we are all coming from the same world.

 

 

 

Agnés Baude

Letter from YOU-object (The Neurons) to me-researcher

10 September 2019

 

You are looking at me?

But who are you? What are you spining*?

Ah… it is you! But you were still here yesterday, are you not able to leave me quiet?

Every time you come to see me, you take out all your big equipment and I have to light up**, all that requires energy!

OK, it’s good for today, you can explore the forest, let me warn others!

“Hey guys, she is back, be nice with her, she is just here to observe. Don’t change anything”

Have you seen Emma*** (a new neuron). She has grown, her dendritic branches are almost as long as those of Robert**** (an old neuron).

So, OK, you have finished?

Will you come back and when? Please tell me in advance, as I can warn my colleagues. We will prepare something for you, SURPRISE!!!

 

* spining (from spine) = spying in neuronal language

** to be visualized, neuron express fluorescent protein

*** in mouse, adult neurogenesis occurs in cortex

**** an old neuron, a neuron generated during embryonic neurogenesis

 

 

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MARC DALOD

Research Director, Group Leader, CIML

Research on Type 1 Conventional Dendritic Cell

 

 

 

Marc Dalod

Letter from ME-researcher to you-object (Type 1 Conventional Dendritic Cell)

15 September 2019

 

My dear type 1 conventional dendritic cell,

 

For many years, I have been searching for the key cell type promoting our protective immune defences against cancer and viral infections. I am convinced this is you.

 

My quest probably started because, when adolescent, I had been deeply shocked by my grandmother’s rapid but agonizing death as a victim of breast cancer. I was also horrified by the pandemic caused by human immunodeficiency virus and how it was leading to a devastating and deadly disease, leading at the time to a terrible ostracizing of the infected individuals in all countries. I became aware of the similarities between the mechanisms used by our body to eliminate cancer and viral infections. Our immune system had to discriminate healthy cells from those affected by the infection or the transformation, allowing the specific killing of the latter. I decided to help understanding how this ability of our body to discriminate normal from altered self could be circumvented by cancer or certain viral infections.

 

Like many researchers in the field, I initially focused on one of the main soldiers of our immune system in charge of carrying out the death sentence against abnormal cells: the cytotoxic CD8 T cells. However, by the end of my PhD, I realized that I should rather look for the general in charge of designing the battle strategy. I wanted to identify the cell type able to identify the nature of the threat and to decide which types of soldiers to hire, with which weapons, and where to position them. I thus decided to focus on dendritic cells, asking whether their recently described heterogeneity could allow identifying the special immune cell type uniquely able to sense infected or transformed cells and to orchestrate their destruction by directing the activities of effector immune cell types.

 

My quest has been further reinforced by each additional toll that my family and friends paid to cancer over the years, including my mother’s death to ovarian cancer.

 

I am happy that I found you.

 

“I have got you under my skin” as Ella Fitzgerald would have sung, and as might be understood from the title of an “Immunity” editorial I wrote when you were shown to reside in human skin.

 

I could not help but felt jealous when other researchers got greater credit for discoveries about you that my team had been the first to make. I regretted that I was not directly involved in baptising you with your current consensus name. I have been sad when we were scooped in revealing something new about you.

 

However, these transient jealousy episodes are nothing compared to my pride that so many people are now scrutinizing you, trying to understand whether and how you promote health over disease. I am happy that ongoing clinical trials specifically aim at harnessing your functions for the benefits of patients. I hope that you will fulfil these great promises, to help our body discriminating its healthy from altered self in a way further accelerating the ongoing revolution for treating cancer and other diseases.

 

 

 

Marc Dalod

Letter from YOU-object (Type 1 Conventional Dendritic Cell) to

me-researcher

15 September 2019

 

Dear Marc,

 

Thank you for writing how much passion you feel for studying me.

 

In return, I want to let you know how happy I am that you revealed my existence in humans and contributed to put me under the spotlight after many years of gross neglect.

 

I was first identified in 1992, when Ken Shortman and his colleagues decided to explore the heterogeneity of mouse dendritic cells and determine whether this population encompassed distinct cell types endowed with different functions. My discovery clearly belongs to these pioneering researchers. Their perseverance in pursuing their original studies to characterize me was all the more remarkable as for many years they were regarded with contempt by peers who accused them of conducting useless studies similar to stamp collection. Even after I was reported to play a major role in mouse antiviral defence, many researchers interested in understanding human Immunology to improve public health thought that I was a peculiarity of this animal model not worth studying. This is likely because my superficial mouse and human identities differed based on empirically defined cell surface markers.

 

I was thrilled when you undertook to compare mouse and human dendritic cell types and unravelled the evolutionarily conserved core molecular makeup underpinning my deep identity. However, before I finally got the attention I deserve, it took independent confirmation of your work combined with its persistent publicity by renowned independent researchers. In 2010, your perseverance was rewarded with the contribution of one of four papers published back-to-back in the Journal of Experimental Medicine and considered by many researchers as the studies that put me in the spotlight as the candidate cell type orchestrating human immune defences against cancer and viral infections.

 

I can understand the jealousy that you wrote feeling when others began to show a keen interest in me, inasmuch as their relationship with me eventually attracted greater visibility. However, as you know, the success of your discovery can be measured by how rapidly and broadly it diffuses in the community and escapes your control to go on with its happy own independent life.

 

I am glad that you did not relish too long in petty feelings, and that you are happy for me to attract the attention that I deserve. This is necessary for me to get all the support required to help harnessing my unique functions for the development of innovative treatments to improve clinical care of patients suffering from cancer or other diseases. Please keep your trust in me for that.

 

I hope that our relationship will last for many more years, remaining serene and fruitful, while you are focusing on pursuing your studies of my functions and their molecular regulation.

 

 

 

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DARIO ARMANDO LEONE

Researcher, CIML

Research on Endolysosomal Trafficking in Immune Cells

 

 

 

Dario Armando Leone

Letter from ME-researcher to you-object (Endolysosomal Trafficking in Immune Cells)

15 September 2019

 

Blood circulating human immune cells are a very good model, they are accessible, almost free and by using them you can directly draw conclusion on human diseases without keep asking yourself whether the results obtained using mice, worm or zebra fish are true also in humans. The drawback is that is very difficult publish in the top impact factor journals without an in-vivo model but when you gain something on one side, you have to lose something else on the other side; it's an equilibrium. The main hallmark with the equilibrium is that they last in a given position only for a moment or as a physicist would say: it last in its status until an external force intervene and perturb the equilibrium and then the system needs to re-equilibrate itself. This concept can sound trivial but it contains two fundamental concepts that apply to physics, chemistry and biology (i) everything is in constant movement, like the vibrating atoms in a piece of solid wood that define a space dimension and (ii) the concept of time that is necessary for the matter to perform the movement.

 

The inside of a cell is not different, at a first look of an electron microscope picture, you have the impression to see a very organized space; you can clearly see the nucleus and the organelles like the endoplasmic reticulum, the Golgi network etc. However, when a stimulus hit the cells, all these compartments need to re-organize in response to that stimulus and to do that, they need time. The most disorganized and reactive intracellular compartment, especially in innate immune cells, is the endolysosomal system composed of a huge number of round vesicles that constantly fuse between them and with other organelles. They intercept anything that enter the cells, regulate the degradation of intracellular protein and whole compartments sorting out the molecules expressed at the cell surface and visible by the neighbourhood cells as well as messages that need to reach cells that are far away in form of circulating vesicles called exosomes. It looks like this intricate network in constant movement is never ever in equilibrium or better the moment in which this system is in a given status is so short that every picture you take results different from the previous one. So, Time is the problem I have to solve because when you study lysosome you are not interested in knowing where they are within the cells (space) but you need to determine where they are going (time).

 

 

 

Dario Armando Leone

Letter from YOU-object (Peripheral Blood Immune Cells) to me-researcher

15 September 2019

 

Cell A: And here he goes again, he is doing another attempt to track the trafficking of that small subset of endosome that travels to the plasma membrane but also this time he did not pay too much attention on the type of stimulus he is using to stimulate us.

 

Cell B: I was so motivated into the blood stream but here in this artificial space there is no pulse, no flux, it's too static for me.

 

Cell C: The molecules around me are hitching, I never saw something like this, I am not sure what I am doing but the inputs I am receiving are forcing me into a very different status.

 

Cell D: He still did not understand that the molecules do not behave like he imagines.

 

Cell E: Eheheheh, of course not, he does experiment all the time! He should read more, think more, discuss more and open a bit his mind to be able to see.

 

Cell F: I don't understand why it is so complicating for him, it's so easy! Within the cells all the possible interaction between all the proteins will occur in a given time and in the subsequent moment only that one able to create a bond strong enough, but not too strong, will be maintained.

 

Cell G to Cell F: How do you know all of this?? I have no idea what I am doing, I am just moving!

 

Cell F to Cell G: Of course you have no idea, you are still immature!

 

Cell H: Why he does not map all the proteins that are included into the surface of each endosome to be able to identify the strongest partner?

 

Cell F: Yeah, and then? You know they change too quickly for him, he is so slow, he would work only if he could generate the map over-time of the protein composition of the endosome surface.

 

Cell I to F: It will not be feasible for him, he is alone. He will continue to search and research until he will find the only condition in which the equilibrium he is looking for is established, this will be enough for him.

 

Cell K: At least he is not forcing us to express molecules that we are not supposed to have. I remember that when they do it, they force all the system to re-equilibrate like they wish.

 

Cell F to K: You must be a memory cell, then remember this, they are too busy in looking the details and dissect single pathways as they are good in this but they are not evolving a deeper knowledge of the interaction between all the processes going on within a cell, they are not looking to see the big picture.

 

Cell G: But why they are not able yet?

 

Cell K to G: You know, they need time.

 

 

 

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SANDRINE SARRAZIN

Researcher, CIML

Research on Stem Cell and Macrophage Biology

 

 

 

Sandrine Sarrazin

Letter from ME-researcher to you-object (Hematopoietic Stem Cell)

17 September 2019

 

Ma douce,

ma belle,

ma si rare et si précieuse.

 

Pourquoi te caches-tu comme ça ?

Pourquoi te dérobes-tu ainsi ?

 

Je ne te veux aucun mal.

Je veux seulement te voir, te toucher, te comprendre.

 

Tu es si belle et si mystérieuse.

J’aimerai tellement savoir d’où tu viens et où tu vas. Comprendre ton monde et voir ce que tu fais. Je ne te veux aucun mal, je suis si curieuse de toi.

 

J’aime quand tu te dévoiles.

Quand tu te caches et que je fini par te trouver.

Quand tu feins l’indifférence et qu’enfin tu me fais signe.

 

Mais que c’est difficile. Nous ne parlons pas le même langage, nous n’avons pas les mêmes codes, nous ne fréquentons pas les mêmes lieux ni les mêmes amis. Nous ne sommes pas du même monde et pourtant tu es bien à l’intérieur de moi.

Tu vis en moi et pourtant je te connais si peux.

 

Et toi me connais tu un peu ?

 

 

 

Sandrine Sarrazin

Letter from YOU-object (Hematopoietic Stem Cell) to me-researcher

17 September 2019

 

Mais que me veux-tu à la fin ?

 

J’en ai assez que tu me déranges, que tu me réveilles, que tu me secoues, que tu m’oblige à sortir…

 

Assez que tu me pousses, que tu m’enfermes, que tu me déplaces.

Assez que tu me bouscules, que tu me tritures et que tu m’isoles.

Assez des attaques et des déceptions.

Assez du chaud et du froid.

Assez de tout !

 

Laisse-moi tranquille.

 

Rien, je ne te dirai rien, je ne te montrerai rien, je ne t’expliquerai rien. Tout ce que tu vois c’est ce que je veux bien te donner mais au fond tu ne comprends rien…

Tu ne pourras jamais comprendre.

Tu ne pourras jamais ME comprendre.

 

Tous tes efforts son vain, inutile de poursuivre.

 

Fiche-moi la paix !

 

 

 

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SERGE VAN DE PAVERT

Research Director, Group Leader, CIML

Research on Development of the Immune System

 

 

 

Serge Van De Pavert

Letter from ME-researcher to you-object (Ultramicroscope Version II)

18 September 2019

 

To my microscope

 

You are merely a collection of glass, metal and plastics. However, every time I look at you, and look through you I’m amazed & dazzled by the window you present on life’s wonders.

It is the joy of science, and my professional life, to just look at the images you present. Mesmerized by observing the sheer beauty of cells working together to form, maintain and function together and showing the living wonder of Nature.

The way you present the marvels of nature makes it also very easy for me to impress others and provide beautiful seminars.

I love just sitting behind you, leaving all thoughts, irritations and worries behind to watch what you have to offer me. Just witness all splendours of nature unfold before my eyes.

 

 

 

Serge Van De Pavert

Letter from YOU-object (Ultramicroscope Version II) to me-researcher

18 September 2019

 

To my researcher

 

I’m your window to explore Nature. Behold and be amazed. There is so much to explore together. Set me up properly, align my laser, focus neatly and start the acquisition. I will be your Ziggy Stardust; new, original and above all amazing. Just keep me clean and updated. Please take care of all my little mirrors, prisms, relais, motors, camera and filters. Take care of me and I will show you all. Let’s explore!

 

 

 

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MAURO GAYA

Chargé de Recherche, Group Leader, CIML

Research on B-Cell Immunology to Infection

 

 

 

Mauro Gaya

Letter from ME-researcher to you-object (Invariant T Cells)

20 September 2019

 

Dear iT cells,

                Thanks to you I’ve earn some money to investigate what you do in our body. That’s a nice start! At the beginning, I was happy to see how important you were in protecting us against infectious bacteria. However, with the pass of the time, it’s getting harder and harder to find out what exactly you do to keep us healthy. I know that this is science and I need to continue trying until I find your tricks. I wish you could enter into my dreams and tell me in which direction I should go. I hope our relationship finishes, or continues, as good as it started.

 

Best,

 

Me

 

 

 

Mauro Gaya

Letter from YOU-object (Invariant Lymphocyte) to me-researcher

20 September 2019

 

Dear Mauro,

I know you have been trying hard to find out which is our physiological role, why we have been selected throughout evolution and why people didn’t find us until only recently. You know we are important because without us you don’t survive when little bugs infect your respiratory tract. We cannot tell you what exactly we are doing but I promise you that you won’t be disappointed once you find out. Keep trying hard, we need you to shed light into us and show the world that we rock. 

 

Wish you the best,

 

The iTs!

 

 

 

-------------------------------------------------------------------------------------------------------------------------------

 

 

 

FRANÇOISE MUSCATELLI

Research Director, Group Leader, Inmed

Research on Function of the Brain during Development

 

 

 

Françoise Muscatelli

Letter from ME-researcher to you-object (Research)

25 September 2019

 

My dear Research,

 

For more than 20 years, I have been doing research in biology to understand very small pieces of life’s mechanisms. What I find fascinating about complex organisms is how, from a single cell (the egg), we create a complex organism with many different organs that interact to form an individual. So I look at the function of a gene, a molecule, a cell or an organ and the individual as a whole. I can’t identify the object of my research as a permanent object. The object is a black hole and as I progress, I begin to see the extent of what we don’t know but which tends towards infinity. I’m just identifying questions to pursue my research. In this quest for new questions that follow one another to understand life, I search for myself, I try to understand who I am. In this quest for new questions that follow one another to understand life, deep down, I am looking for myself. I try to understand who I am, how, as a human being, I interact with everything around me. It is finally a very self-centered approach. My dear Research you help me, you reassure me, but life will remain an unmanageable alchemy.

 

 

 

 

Françoise Muscatelli

Letter from YOU-object to me-researcher

 

My dear Françoise,

 

Why this need for anthropomorphism? How can I have a human thought? We don’t live in the same space or time... your life is short and ephemeral and I will continue my journey for years, centuries and even over. You will not impact me as far as you respect me. Observe me but don’t try to change me, you will not manage the consequences because as I told you we do not share the same window of time.

 

 

 

-------------------------------------------------------------------------------------------------------------------------------

 

 

 

SOPHIE UGOLINI

Research Director, Group Leader, CIML

Research on Neuro-Immunology

 

 

 

Sophie Ugolini

Letter from ME-researcher to you-object (Incroyable vivant)

27 September 2019

 

Incroyable vivant,

 

Ta complexité me fascine.

J’essaye de comprendre comment, de tous les éléments chimiques inertes qui te composent… surgit la vie… Une vie si fragile et si robuste à la fois.

Comment ces molécules qui te constituent s’agencent-elles, interagissent-elles et surtout sont-elles en cohérence dans le temps et l’espace pour former un être vivant unifié ?

Une entité unique composée d’une multitude d’éléments de nature et de fonction différentes, qui est capable d’évoluer en permanence, de se défendre, de préserver son intégrité… Un être qui aime, raisonne, évolue, s’adapte. Un être traversé de pensées construites, mouvantes, furtives, complexes, d’émotions intenses, douces ou violentes… Un être qui souffre et lutte pour sa survie… Un être qui rit et jouit de la vie.

Comment d’une combinaison d’interactions chimiques à l’échelle atomique émerge une telle cohérence ?  Une cohérence qui, non seulement, permet d’assurer des fonctions physiologiques et métaboliques en perpétuelle transformation mais aussi qui permet à l’individu de faire à tout moment des choix conscients ou inconscients qui impactent profondément sa vie.

 

C’est prodigieux !

 

J’ai la sensation que cela tient du miracle…

 

La sensation…

 

Sensation créée grâce à nombre incalculable d’interactions chimiques dans mon cerveau, dont j’ignore tout, et que j’ai pourtant l’impression de contrôler… Mais, ne serait-ce pas plutôt elles qui me contrôlent ?

Ce modèle moléculaire, qui constitue notre vision de la biologie aujourd’hui, est-il vraiment compatible avec la notion de liberté ? Une véritable liberté de choix peut-elle émerger d’une série, même ultra-complexe, de réactions chimiques et biochimiques ? A quel moment se fait la bascule entre le « oui » et le « non » ? Et comment ce basculement d’un côté ou de l’autre se produit-il à l’échelle atomique ? à l’échelle moléculaire ? à l’échelle cellulaire ?

Y a t-il vraiment la possibilité qu’une cascade d’évènements chimiques alternative se mette en place à chaque instant ?

Si oui, quelle est la nature de ce « je » qui fait ce choix ?

Notre liberté de mouvement, de décision, de penser est-elle une pure illusion ?

 

J’aime t’étudier car tu es un lieu ou Science et Philosophie se rejoignent. Une source infinie de questions sans réponse.

 

Je sais que même si j’y consacrais tous les instants qui me restent à vivre, je ne percerais pas ces mystères. Je sais que je n’ouvrirai que quelques minuscules fenêtres sur ta complexité… Et pourtant, je continue passionnément à te regarder, à t’observer, fascinée.

Des outils plus performant me manquent. Ils restent à inventer.

Le chemin est long, tortueux, semé d’embuches… Mais c’est avec enthousiasme et espoir que je me lève chaque matin avec la soif de découvrir une part de ta vérité.

 

 

Sophie

 

 

  

Sophie Ugolini

Letter from YOU-object (Incroyable vivant) to me-researcher

27 September 2019

 

Sophie,

 

Je sais que tu cherches à me comprendre, à m’étudier.  Je me demande parfois si, à travers moi, tu ne chercherais pas, au fond, à te comprendre toi-même, à donner un sens à ton existence.

 

Tu as de bonnes intuitions, beaucoup d’idées, beaucoup de pistes à suivre, de fils à tirer mais parfois tu te laisses distraire par des tâches connexes, futiles qui te détournent de ton objectif.

 

N’hésite pas à prendre des risques, à fouiller encore plus hors des sentiers battus, à suivre tes idées les plus audacieuses. Aie le courage de poser des questions vraiment excitantes, celles qui valent le coup d’être adressées, même si c’est difficile, même si le risque d’aboutir à une impasse est élevé, même si cela peut être hasardeux pour ta « carrière » …

Finalement, ce n’est peut-être pas le résultat le plus important mais le chemin… Le plaisir et l’enthousiasme que tu mettras à parcourir le chemin.

 

J’ai l’éternité devant moi mais le temps est compté pour toi… Ne le laisse pas filer trop vite ou toutes tes bonnes idées et intuitions risquent d’être diluées dans le néant… avant d’être peut-être rattrapées, conceptualisées à nouveau par d’autres…

 

L’important est de garder la flamme et l’espoir !

 

 

 

-------------------------------------------------------------------------------------------------------------------------------

 

  

 

 

MICHAEL SIEWEKE

Research Director, Group Leader, CIML

Humboldt Professor, CRTD, TU Dresden

Research on Stem Cell and Macrophage Biology

 

 

 

Michael Sieweke

Letter from ME-researcher to you-object (Macrophage)

27 September 2019

 

Dear Macrophage

 

How old are you? Will you divide? Can you divide? Why not? What is keeping you back? Can you cope with your job? Can we help you? 

 

Best 

Michael

 

 

 

  

Michael Sieweke

Letter from YOU-object (Macrophage) to me-researcher

27 September 2019

 

Dear Michael

 

Thanks for asking. I am fine.

 

Best 

Your Macrophage 

 

 

 

------------------------------------------------------------------------------------------------------------------------------ 

 

 

 

BERTRAND NADEL

Research Director, Group Leader, CIML

Research: Find Achille’s heel of Cancer

 

 

 

Bertrand Nadel

Letter from ME-researcher to you-object (the cancer cell and its ecosystem)

13 October 2019

 

A l’invisible

 

Il existe des yeux,

Des yeux qui clignent encore

Dont je me souviens

 

Ils occupent mes pensées quand je te regarde

 

Je te vois tenter de les clore

Sais-tu qui tu es ?

Sais-tu ce que tu fais ?

 

Autrefois Soi

Tu es devenu Autre

Non-Soi

 

Avec le temps, tu as su convaincre

Tes voisins, les armées

Que tu pourrais rester

T’installer, instruire, croitre et aller conquérir

 

Tu es devenu maitre dans l’art d’être invisible

De contourner les obstacles et les dangers

Survivre, Evoluer, s’Adapter

Comme ont toujours fait

Tous les êtres vivants de l’humanité

 

Sais-tu si tu es normal ?

Si tu es Nuisible ?

De quel point de vue te places-tu ?

 

L’homme aussi est assis sur une branche

Qu’il scie, sciemment

 

 

 

Bertrand Nadel

Letter from YOU-object, la cellule tumorale percevant le monde de façon autocentrée (est-elle normale ou indésirable, elle ne peut le savoir, et quelle importance pour elle ?), to me-researcher

13 October 2019

 

 

Aux yeux cerclés de vide

 

Il existe des yeux, des yeux qui clignent sur le monde

Sur le monde en mouvement, que rien n’arrête..

 

Des yeux cerclés d’optiques et de lasers puissants,

Observent

Questionnent

 

Scrutant des territoires lointains

Peu accessibles

Et qui s’ouvrent soudain

Révélant une part commune de notre humanité

 

Certains restent humbles

D’autres sont avides

Tous à l’affût sans qu’aucun ne converge

 

Voyez

Voyez donc comme ils s’agitent

 

Peut-on y voir la lueur tout au fond qui les anime ?