The shared emotion behind art and science

The shared emotion behind science and art

 “Art and science aim to unveil the universal perception of the subjects they examine.”

Both art and science seek to impact humanity by  donating a meaningful story. Their efforts are consistently focused in reflecting and understanding the nature of our world. They both move fast, while intending to remain time-less. Art, as an universal language, helps science to be more accessible to a broader public. Science in return, has been a source of inspiration for many artists throughout history. Both have faced, and still do, endless difficulties in their mission to shed a light of truth. They require sacrifice, resilience, and patience.  Both are exciting, unpredictable and consequential. Their resemblance increases the more one thinks about them.

What I just wrote, is nothing new. We have heard of the bright sides of art and science, and we know first hand, how beautiful they can be. To give it a twist, I will dive into some of the common struggles that artists and scientists share during their discovery journey. A small reminder before the next lines: this is of course, an opinion article. Feel free to skip the chapters you don’t see your self reflected into.

The shared emotion behind science and art
Chapter one: self doubt

To create, does not come with ease. To be able to stand out in this journey, is an even more challenging task. The new-born artist, as the new-born scientist,  enter a world where our own self-worth is often at stake. We mostly do so with innocence and a hand full of  ideas, confidence and dreams. Inevitably during the first years of our career, and for as long we  remain being artists and scientists, our  ideas and discoveries will undergo a merciless process of trial and error. Our work will become an absolute reflection of how capable, bright, and resourceful creators we are.

I might be adding some theatricals to embellish this thought. But, wouldn’t you agree? When we are working on an experiment over and over and we do not succeed..  one might start questioning their own capacity to perform it. One might start to fear of what their supervisor or colleagues might think.  Am I good enough?  I presume, you can think of some intrusive thoughts that hunt us in this situations.  I would imagine, that artists go through the same experience when they are trying to figure out, for example, which is their own style. They might doubt themselves. They might get hit by the popular “impostor syndrome”. And sometimes, so do we, scientists.

Chapter two:  uncertainty

Artists and scientist do not only share a goal, but we also face a sense of vulnerability and uncertainty that often threatens our work. The principle behind, is that regardless our efforts, there is no guarantee, to achieve what we intend to.

An artist can have created with an imaginative hand and can have persisted until shaping the exact shade of emotion they wanted to capture. Nevertheless, it is likely, that asides from the closest circle of people surrounding them, no one will ever appreciate their work. Artists need to live with the possibility of their piece never being shown at a gallery or complimented by an expert. In in other words, that their work does not become transcendental.

In the exact shape, only a small percentage of scientists will make it to a big name and will be able to deliver an essential missing piece of information or develop a novel technique. Not every scientist will be able to publish in the highest impact factor journal.  For some of us, a small contribution to a bigger picture will be the work of our lives.

We do know, that uncertainty can be one of the reasons why remaining an artist or a scientist during the years, is considered by many, something to admire.

Chapter three: time

 For artists and scientists: Days are weekends that are months. Evenings are hours that are already mornings.

A lot of time. Not enough time

I think there are no words needed for this chapter.

Chapter four: acceptance

Both artist and scientists have to face this chapters at some point of their career. They have to face many other more, that I have intentionally omitted.

To do so, I think we need to feel fulfilled by our life choice. I have heard that often artists see their creation as a part of themselves. I would say, we scientists relate to our work in a very similar way.  The artist and the art, and the scientist and the science. It is a one of a kind connection that makes us accept all of this facts, with a blink of an eye.

Chapter five: success does not equal fame

And now, a small reflection that might help, when are stuck in one of this chapters.

That artists or scientists do not become a recognized figure, does not mean that they did not have brilliant ideas and a fantastic story to tell. Think of the times, when artists and scientists have brought concepts that the world was not ready for yet. For your inspiration:

 Ada Lovelace (nationalgeographic.com)

Greco (Doménikos Theotokópoulos). Museo Nacional Thyssen-Bornemisza (museothyssen.org)

 

There are difficulties in science that are beyond of our control. Same applies to artists. I am sure you can also think of a couple of examples.  It repeatedly happens that an artist and scientist might have the brightest idea but lack the resources to conduct it. Other times, they might have perfected their story, but not have the opportunity to make it available to the desired public. Or it might not be recognized in the way it deserves. The list goes on and on.

I am under the impression, that success, does not often correlate with the personal capacity of the artist or the scientist to shape a new story into this world. And I think, that keeping this in mind, might actually help us avoid falling into these chapters.

 

With this, the end of my article.

 

An unknown artist for my take on art and science

The shared emotion behind art and scienceO.M.

In my (humble) opinion,

Art and science, to be truly enjoyed, should be done without any higher expectation of fame or greatness. That is why, in my take on enhancers in art, I would like to stay truthful to my thoughts. I intend to give the opportunity that Enhpathy offers to a new artist. I hope that by doing this, I will be able to convince you, that artists and scientists go hand in hand in the journey of creation.

Read more

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Current challenges in understanding the role of enhancers in disease

Enhancers play a central role in the spatiotemporal control of gene expression and tend to work in a cell-type-specific manner. In addition, they are suggested to be major contributors to phenotypic variation, evolution and disease. There is growing evidence that enhancer dysfunction due to genetic, structural or epigenetic mechanisms contributes to a broad range of human diseases referred to as enhanceropathies. Such mechanisms often underlie the susceptibility to common diseases, but can also play a direct causal role in cancer or Mendelian diseases. Despite the recent gain of insights into enhancer biology and function, we still have a limited ability to predict how enhancer dysfunction impacts gene expression.

In this Perspective review published in the Nature Structural & Molecular Biology journal, the ENHPATHY researchers discuss the major challenges that need to be overcome when studying the role of enhancers in disease etiology and highlight opportunities and directions for future studies, aiming to disentangle the molecular basis of enhanceropathies.

Read more

 

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Chronic inflammation decreases HSC fitness by activating the druggable Jak/Stat3 signaling pathway

New publication by Alberich-Jorda M and Sladana Kosanovic in EMBO reports.

Chronic inflammation represents a major threat to human health since long-term systemic inflammation is known to affect distinct tissues and organs. Recently, solid evidence demonstrated that chronic inflammation affects hematopoiesis; however, how chronic inflammation affects hematopoietic stem cells (HSCs) on the mechanistic level is poorly understood. Here, we employ a mouse model of chronic multifocal osteomyelitis (CMO) to assess the effects of a spontaneously developed inflammatory condition on HSCs. We demonstrate that hematopoietic and nonhematopoietic compartments in CMO BM contribute to HSC expansion and impair their function. Remarkably, our results suggest that the typical features of murine multifocal osteomyelitis and the HSC phenotype are mechanistically decoupled. We show that the CMO environment imprints a myeloid gene signature and imposes a pro-inflammatory profile on HSCs. We identify IL-6 and the Jak/Stat3 signaling pathway as critical mediators. However, while IL-6 and Stat3 blockage reduce HSC numbers in CMO mice, only inhibition of Stat3 activity significantly rescues their fitness. Our data emphasize the detrimental effects of chronic inflammation on stem cell function, opening new venues for treatment.

Link on the publication

 

 

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Scientific communication 101: A creative strategy to convey the wonder of your research

Art and science are intuitively perceived as polar opposites: subjective versus objective, creative versus analytical. However, history provides us several examples of pivotal figures in science that have been able to wear the shoes of the scientist and the artist at once.

3 giants of art and science and their works

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

For instance, Santiago Ramón y Cajal (1852 – 1934), Spanish artist, photographer and neuroanatomist, dedicated fifty years to the study of the nervous system, producing a plethora of brilliant illustrations out of his observations. In one of his major writings, ‘The neuron doctrine’, he presented his theory considering neurons as individual cells sending and receiving information. This theory, recognized today as the basis of modern neuroscience, yielded in the assignment of Nobel Prize in Physiology or Medicine in 1906.

In addition, Maria Sibylla Merian (1647 – 1717), today acknowledged as one of the most important female scientists of the ‘Age of Reason’ and pioneer of modern entomology. Her observations helped dispel the popular belief that insects spontaneously emerged from mud. Moreover, her detailed descriptions and paintings of exotic insects, portrayed for the first time in their habitats, registered on-site during her travels to South America, inspired generations of artists and ecologists.

Finally, Leonardo da Vinci (1452 – 1519), among the greatest polymaths of the Renaissance, pursued art and science by following his boundless desire for knowledge and artistic expression. His artistic expression was not limited to drawings for inventions and experiences, but also lead him to the generation of masterpieces appreciated worldwide, such as Mona Lisa and Last Supper.

 

“To develop a complete mind: Study the science of art; Study the art of science. Learn how to see. Realize that everything connects to everything else.”
– Leonardo da Vinci

 

As a young researcher in the ENHPATHY consortium, I am invited to stand on the shoulders of these giants and explore the impact of art on the communication of the value of scientific efforts aiming to unravel the intricate world of gene regulation to the general public.

At the beginning of this adventure, I am looking forward to meet the chosen artist for an initial chat about my PhD project. If you are interested in this challenging experience, you can continue to follow the Enhancer in Art blog, where you will find interesting updates and the final result of this curious experiment.

 

Links for further reading:

 

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ENHPATHY ESRs visit the Novartis Institutes for BioMedical Research (NIBR)

The Novartis Institutes for BioMedical Research (NIBR) is the innovation engine of Novartis. NIBR’s Scientists collaborate across scientific and organizational boundaries, with a focus on powerful new technologies that have the potential to help produce therapeutic breakthroughs for patients.

Visit NIBR

Learn more about the visit program

 

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Science & Art collaboration: the starting up of Enhancer in Art

Encounter with Artist

Zijun is a master student who study in École supérieure d’art d’Aix-en-Provence Félix Ciccolini (ESAAIX), France. Before she switched into art, she was a product manager of IT company in China and Japan. The first time we met happened in the art exposition of Jeff Koons in Europe and Mediterranean Civilization Museum of Marseille. She introduced me an initial perspective on how to view art exhibitions that I had never set foot in. We talked each other about our working field, and realizing the potential collaboration because we both interested in cross-disciplinary collaboration.

Explorer in biological lab

So we started to explore the possibility of collaboration. We arranged a coffee meeting with Davide (ENHPATHY project manager) in the library of campus. We discussed the program plan of Enhancer in Art, what artist need from art part, what we can provide from science part and how to start up step by step. It’s very well and fully-discussed meeting between researcher, artist and manager. For knowing biology working better, I invited Zijun to visit our laboratory to show our daily scientific work. Zijun showed great interest in our daily biological experiment stuff and some materials we always ignored.

Researcher in artist working shop

In a campus opening weekend, I visited Zijun’s art college and working place in Aix-en-Provence, which locate in hometown of the famous Post-Impressionism artist, Paul Cézanne. It’s an impressive and novel conception explosion experience for me, as a person outside of art. The art working direction in ESAAIX involve all kinds of stuffs for material exploring and conception construction, like materials of plastic, wood, steel, silk, paper, ceramics; the conception of human body structure, gender, electronic games, machinery, 3D printing; the form of sound, visual, action, sense of touch. The painting only takes small part of modern art. All of these opened my mind to explore the crossing between biology research and art. And also let me know what kind of materials could be useful for artist and what kind of space and environment condition required by special art work.

Generally, I felt different kinds of working possibility and exciting for the following work. In the next, we are going to write a general proposal and exchange our idea for the concrete material, conception and format of Enhancer in Art.

Artist working shop and art works in creating
ESAAIX campus opening weekend

ESR, artist, KOM agency founder, scientist in Friche la Belle de Mai, Marseille

 

writing and photos: Jing Wan

modified: Zijun Feng

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The collaborative nature of artists and scientists

The truly collaborative nature of artists and scientists lies far from pop illustrations of the double helix in fancy journals. At some point, I had a temptation to create a scientific colouring book for kids that could be even published. However, I believe that talented kids will find another way to Science. I’m intended to dedicate my Enhancer in Art project to a more burning question for me.
In “The Nature of Paleolithic Art”, Dale Guthrie proves that most prehistoric cave arts were created by testosterone-fuelled boys, driven by sex and violent ideas. Interestingly, not much has changed, and we still see the same topics depicted on the street walls by modern young people. No taboos or other limiting factors could stop this ugly (or natural?) and uncontrolled energy from developing in punk rock, industrial and noise music in the 20th century (check “England’s Hidden Reverse: A Secret History of the Esoteric Underground” by David Keenan). What should we expect now from the metamodern era?
While Science keeps accumulating knowledge to move the borders further, Art, often based on poorly supported cultural norms, set up more and more experiments to refuse or even destroy them.

Leon Theremin plays theremin (Moscow, 1954)

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ART OF SCIENCE, SCIENCE OF ART ….

People often perceive science and art are at the impassible spectrum, although it is a matter of observation and interpretation. For humans, the most effective method for interpreting the world around them is Visual Art. From prehistoric to the modern world, illustration has been the most effective way to explain the world around us and comprehend complex information clearly and concisely. Therefore the field of science and art are intimately connected. The detailed illustrations by artists and scientists significantly convey the knowledge and understanding of years of scientific research describing new species, anatomy and behaviour, complex processes, new technologies etc. This blog is dedicated to recognising SCIENTIFIC ILLUSTRATORS, a fascinating intersection between science and art.

 

“Science illustrators are artists in the service of science.”

– The Guild of Natural Science Illustrator

 

The practice of scientific illustration is an accurate and often artistic visual interpretation of a concept or idea aimed at the target audience. Therefore, A Scientific illustrator is an artist who has advanced education and specialised training in art, design, visual technology, media techniques, science, medicine and theories related to communication and learning. They collaborate with scientists, physicians, and other content specialists. They serve as a visual translator of complex technical information to support education, publishing content, medical and life science research, patient care and education, public relations, and marketing objectives. Apart from this, they can often function as content developers, creative directors, consultants to law firms/MNC and administrators within the general field of biocommunication. Many of them work as freelancers and emerge as entrepreneurs in the marketplace.

 

Scientific illustrators’ profession may not be as well recognised as teachers, astronauts or doctors since, after looking at the work of scientific illustration, many people assume that it is just a computationally created piece of art that you see in science textbooks, posters and advertisements. However, creating an illustration is a pretty extensive and complicated process, given they do a lot of reading, research and work with experts from all different fields. Creating an illustration is like starting with an idea, writing everything, thumbnails and brainstorming. It goes through various versions, drafts, corrections, and proofs until it ends with a final illustration.

 

As part of the “Enhancer in Art” science’art program, all the ESR are committed to finding a highly motivated artist to be involved in the project where they have to understand the depth of the project and bring artistic perspective to the edge that everyone can devour. Keeping this motivation in mind, I explored the plethora of scientific art and came across Tejeswini Padma, Professional Medical Illustrator (https://www.tejeswinipadma.com/). She is an award-winning medical Illustrator who creates bespoke and accurate artwork, animation and design for the medical, scientific and legal fields. It was amazing to meet her and be fascinated to see the medical illustration she had worked on. Lastly, here is one of her artwork I would like to present.

 

“When Nano meets Polymer” – Two miscible polymers interacting are shown by the boys playing. When subjected to extreme temperature changes, the polymers’ phase separate’, portrayed by the rift between the boys. The addition of nanoparticles (chocolates, candies and other goodies) helps keep these polymers together for longer, even in harsh conditions. Therefore the boys are back to playing together.

 

A classical Example of Scientific Illustration

Image Credit –
Tejeswini Padma, MS
Professional Medical Illustrator
Website: https://www.tejeswinipadma.com/
Linkedin: https://www.linkedin.com/in/tejeswini-padma-42b4b086/
Instagram: https://www.instagram.com/tpadma_illustration/

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The Link Between Art and Science

Many people believe scientific investigation only involves analytical thinking – a purely logical endeavor that is, unlike fine arts, free of any form of creativity. However, I have always seen scientific research and its integral problem-solving process as an inherently creative process. To me, the laws of nature and the analytical framework given by the scientific method only set the boundaries within which a scientist or engineer can act creatively to answer a question or solve a certain problem – much like artists are limited by their medium of choice. While our imagination may, to a certain extent, go beyond worldly constraints, painters will be limited by the canvas and the colors available to them, sculptors cannot go beyond our three dimensions, and musicians are bound to the tonal range of their instrument; to name but a few examples.
However, boundaries can also give rise to creativity, in art as well as science. The art is to fully express a conceptual idea despite the limitations.

A stunning example of creative thinking in science and its importance are Einstein’s thought experiments, most notably those related to his theory of relativity. At the time, recent developments in the field of electromagnetism (related to the Lorentz transformations) led to a mathematical model which implied that time and space would not be absolute. Inspired by this, Einstein considered various scenarios only using his imagination, with the mathematical model setting the creative boundaries. Without performing any hands-on experiments or setting foot in a laboratory, he formulated the theory of relativity. In his thought experiments he visualized beams of light that he is chasing, moving trains struck by lightning, or accelerating elevators and based on that reasoned out physical consequences. Through creativity and imagination, a scientific theory was born which still helps us in our daily lives (e.g., location tracking on our phones) and predicted phenomena we only managed to observe almost one hundred years later (gravitational waves were first observed directly in 2015).

Thus, I see art and science closely linked, with creative and imaginative aptitude forming the cornerstone for both – but one pertaining to emotion and the other to reason.

With Enhancer in Art, I hope my research will be translated from the world of reason to the world of emotion, therefore making it more approachable. This might help the layman, perhaps deterred by the analytical framework of science, to understand the creative process that science shares with art.

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Role of art in a science-oriented world

Modern industrial and post-industrial societies are increasingly relying on the scientific method for advancement of economy, citizen well-being and even culture. This shift from a more intuitive or, some would say, primitive way of thinking and decision making has undoubtedly benefited human race by accelerating technological progress and giving us an instrument for revealing the truth about the world in an unbiased manner. This understanding of universal usefulness of science is illustrated by the fact that most developed countries invest a great deal of money into various scientific programs without any obvious economic incentive. The explanation for that being the fact that long term positive effects of scientific development far outweigh the contemporary encumbrance of having to support costly research infrastructure. This atmosphere of increasing rationalization seemingly leaves little place for art to be of any significant value in the modern world.

This simplified view of the world, however, ignores major limitations of the scientific method. One being it’s focus on falsifiability, which in conjunction with technological limitations of our times effectively precludes the application of science to most of imaginable questions. Another big problem is the fundamental inconsistency of the mathematical framework that is at the heart of all modern science. This surprising quality discovered by Kurt Gödel in the first half of the twentieth century demonstrates a fundamental flaw in our understanding of logic and shows that no amount of technological or theoretical progress will provide us with a fully consistent view of the world. At the same time there are less metaphysical problems stemming from overspecialization. While overall scientific knowledge consistently grows, the fraction of it that can be internalized by any given person shrinks day-by-day. Each field grows deeper and deeper in it’s understanding of the subject, develops new jargon and narratives. As a result it is often a challenge to effectively communicate this information between the members of different fields, let alone between the scientists and general public.

But even if there are some cracks left to fill, could art be of any use in this endeavour? After all, art often serves a utilitarian function: as simple decoration, meaningless distraction, a profitable investment, a communication tool, at best a medium to share empathy and facilitate psychological support (nothing a future anti-depressant or anxiolytic can’t handle much more easily). The problem of overspecialization is also quite prominent in the art world. As any art form develops in it’s own rich historic and cultural context it acquires (deliberately or otherwise) footprints of the past: references to historic events, callbacks to previous works of art, callbacks to the aforementioned callbacks and so on and so on. A resulting work of art can become overburdened with information that without a substantial prerequisite knowledge is unreadable. To put simply, for a layman these pieces of art make as much sense as a physicist droning for hours about tensor products.

So, is there a role that art can play to help us with our understanding of reality? Does it need one? That I simply do not know. But being involved in the Enhancer in Art project I’m hoping that the process will help me to judge for myself.

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Cell signaling and gene regulation review

 

Cell signaling plays a crucial role in development and organisation of every tissue in a multicellular organism. Signaling pathways tend to result in the activation or inactivation of transcription factors (TFs), often through post-translational modifications of the TF, typically without altering their DNA binding specificity.

The TFs therefore are a subject to research from both fields of cell signalling and gene regulation. However, studying them from either point of view provides researchers with significant challenges largely caused by different technical limitations of each respective field.

Here I want to highlight a review we co-authored with our colleagues from EBI that illustrates many of these difficulties and highlights the importance of multi-omics studies to bridge these two aspects of TF biology in the future.

 

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A Sensory Play

About the artist

 

 

With the bases of my Enhancer in art project in place, the next step was to find an artist whose vision and motivation aligned with not only me but the spirit of the project. When I set out to look for an artist, I had no idea that I would find one, an hour away from me. Soledad is a scientist and artist that has illustrated and designed more than twelve books, scientific dissertations, and journal publications. The trajectory of her life intertwines art and science at a very early age which goes on to diverge as she pursues a career in molecular biology. Eventually, in 2016, she finds solace in harmonising her passion for art and science which defines her brand now.

About the art

Soledad wanted to give the viewers an immersive visual and acoustic experience to convey the gravity of the project. With the installation art, she wants to emphasise how the disease is difficult to spot and analyse due to its intricate complexities. Her installation would encourage viewers to look at the disease from a different perspective.

The art piece encapsulates the serene nature of human development while eerily singling out the deteriorating heart. It introduces the experience with the banality of everyday lifestyle while the imminent detriment creeps in through an audio-ocular sensory play. The piece perfectly covers crucial aspects of the disease and sophisticatedly emphasises the weight of the problem.

The art aims to convey the importance of such research by giving viewers an experience to remember. With Soledad’s enthusiasm and vigour, I am looking forward to seeing everything come together.

 

Website: https://soledad2112.com

Linkedin: https://www.linkedin.com/in/soledadordonez/ 

Instagram : https://www.instagram.com/soledad2112/?hl=en 

 

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Epromoters: The regulation of gene expression is no longer a binary issue

In all mammals, the cellular operation responsible for the maintenance of homeostasis, specifically of all the physiological balances ensuring the vital functions of an organism, is dictated by the reading of information carefully preserved in the genetic heritage or DNA. The expression of a gene that will code for one or more proteins of interest is therefore a strategic step, controlled by the presence on this DNA of regulatory sequences, which in the event of malfunction, can cause the occurrence of serious genetic pathologies, such as inflammation or auto-immune diseases.

 

Listed in two distinct families according to their locations near or far from the genes that they regulate, researchers speak of promoters or enhancers, respectively. These sequences are scrutinized by the scientific community in an attempt to arrive at a better understanding of the complexity of their modes of action. The latest work from a research team within the TAGC laboratory (Theories and Approaches to Genomic Complexity, Inserm/AMU), led by Dr. Spicuglia and published in the journal Nature Communications have recently shed new light on the role of a particular family of promoters called Epromoter that are involved in gene regulation, but this time, without particular location criteria.

Read more

 

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Epromoters: The regulation of gene expression is no longer a binary issue

In all mammals, the cellular operation responsible for the maintenance of homeostasis, specifically of all the physiological balances ensuring the vital functions of an organism, is dictated by the reading of information carefully preserved in the genetic heritage or DNA. The expression of a gene that will code for one or more proteins of interest is therefore a strategic step, controlled by the presence on this DNA of regulatory sequences, which in the event of malfunction, can cause the occurrence of serious genetic pathologies, such as inflammation or auto-immune diseases.

 

Listed in two distinct families according to their locations near or far from the genes that they regulate, researchers speak of promoters or enhancers, respectively. These sequences are scrutinized by the scientific community in an attempt to arrive at a better understanding of the complexity of their modes of action. The latest work from a research team within the TAGC laboratory (Theories and Approaches to Genomic Complexity, Inserm/AMU), led by Dr. Spicuglia and published in the journal Nature Communications have recently shed new light on the role of a particular family of promoters called Epromoter that are involved in gene regulation, but this time, without particular location criteria.

With an enlarged scope of action, Epromoters are forcing scientists to reconsider the origin of certain genetic dysfunctions

For the uninitiated, deoxyribonucleic acid, or DNA, a true emblem of modern biology responsible for the mechanisms of reproduction, mutation and gene expression, is a molecule discovered in the 1940s, whose double helix structure was revealed to the scientific community in 1953 by the famous duo Watson and Crick.

With the advent of ‘Omic’ technologies and new computing powers, researchers have constantly pushed the limits of knowledge on the complexity of this molecule, both organizationally and functionally. Three dimensional models of chromatin, the structure within which DNA is packaged, at the heart of epigenetics research programs, have replaced linear and simplistic models that tended to reduce the regulatory sequences of genes to simple switch boxes, attached to a gene, which the cell just needed to activate its button to influence the production of a protein.

Research work, which has enabled new actors to be characterized that are capable of inducing or repressing the activation of a gene from afar, has taken into account the complex re-arrangements in the space of the double helix, placing in near proximity certain regions that are several thousand base pairs apart, like a thread in a ball of wool.

A pioneer in the characterization of a group of promoters also involved in the regulation of distant genes (ref –> Genome-wide characterization of mammalian promoters with distal enhancer functions https://doi.org/10.1038/ng.3884), Dr. Spicuglia’s research team has taken a new step by confirming in this publication – notably thanks to functional studies involving key cellular players in the immune response, such as macrophages – the particular mode of action of Epromoters during the response of the cell to a stress signal or an inflammatory response.

Triggered by the body following an exogenous (infectious or traumatic) or endogenous attack, the inflammatory response is a component of the body’s immune response to a danger signal. Under normal conditions, it constitutes an adapted and controlled response by multiple regulatory systems, thereby contributing to the natural defense process and tissue repair. When the inflammatory reaction is inappropriate or poorly controlled, it becomes aggressive, doctors then speak of acute or chronic inflammatory syndromes or diseases, the latter being the third cause of death, after cardiovascular diseases and cancers.

Interferons, intercellular communication molecules and key players in the response to a stress signal

During a viral infection, type I interferons (IFNA/IFNB) are produced, proteins of the cytokine family which, by binding to their targets, will trigger an innate or immediate immune response, to limit the spread of the virus in the body. Secreted into the extracellular medium, IFNs are molecular messengers capable of docking in a specific way with membrane receptors to trigger a cascade of signals inside the cell; firstly in the cytoplasm, then in its nucleus, where they induce the expression of interferon-stimulated genes (ISGs).

“An insufficient or inappropriate interferon response will not be able to contain the replication of the virus or may promote a pathological immune response (for example, a runaway immune system, as seen in severe forms of Covid-19),” says Dr. Spicuglia.

Epromoters, multi-function regulating elements

The use in this study, of the so-called “high-throughput gene reporter system” technique for analyzing thousands of genome sequences presenting promoter or enhancer characteristics under different stimulation conditions, enabled Dr. Spicuglia’s team to show that the Epromoters are capable of not only locally recruiting all the factors involved in the regulatory mechanisms of ISG gene groups, but also of establishing connections with other distant genes during the induction of the cellular response to stress signals or during an inflammatory response.

“This observation now requires us to go further in the study of the mode of action of these regulatory sequences involved in inflammation to better prevent and treat the many diseases associated with it, such as atherosclerosis, cancers, auto-immune diseases and infections,” concludes Dr. Spicuglia.

 

Link to Nature Communications November 21 post: https://doi.org/10.1038/s41467-021-26861-0

Download this article here

Editorial: Jean M. Grangeon – KOM Agency
Review: Dr. Salvatore Spicuglia
Translation: David Williams

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EMBO Workshop. Enhanceropathies | 06 – 09 October 2021

Understanding the mechanisms of eukaryotic gene regulation is essential not only from a theoretical scientific perspective. Knowledge of the precise mechanisms driving interactions between regulatory elements of a two-meter long DNA packaged inside a tiny nucleus is crucial for a better understanding of disease mechanisms. The gained insights ultimately may bring us closer to developing targeted strategies and solutions in the clinical setting.

During the EMBO Workshop, the leading scientists presented their recent works covering a broad range of topics in the field of enhanceropathies. Participation in the workshop allowed me to deepen my knowledge of enhancer biology and explore different computational and experimental approaches for studying the role of enhancers in development and disease.

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Enhanceropathies: Understanding enhancer function to understand human disease (EMBO workshop) 6-9th October 2021

During the EMBO workshop “Enhanceropathies: Understanding enhancer function to understand human disease” held in Santander (Spain)I had the pleasure of attending many interesting talks everything related to “enhanceropathies”.

No less important, I showed the recent results of my project during the poster session.
I am pleased to have aroused the interest of many colleagues who asked me interesting question and given above all useful advice.

Very good environment and excellent experience shared with other colleagues of consortium.

 

 

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EMBO Workshop Enhanceropathies, Santander Spain (6-9 October 2021)

I participated in the EMBO Workshop Enhanceropathies: Understanding enhancer function to understand human disease organised in Santander, Spain. I had the opportunity to broaden my knowledge and present the progress of my ongoing project through a poster titled: Dissection of enhancers community regulating the PPARG locus during adipogenesis.

Also, it was a great chance to meet PhD fellows from Enhpathy consortium. 

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Enhancer in Art: The journey of Natsuda’s PhD — Artist introduction

It takes me quite sometimes to figure this project out after I got the topic of “Enhancer in Art” from the ENHPATHY communication team. In brief, we would like to “publish” our research project on “enhancer” to more public eyes through “arts”, instead of a publication as usual.

After sat on it for quite a while, all the pieces of the puzzle were in place. For me, even though I have the concept of what to do since the beginning, doing research is still full of trial, failure, learning, adjustment, and, of course, readjustment. What I would like to present in my enhancer in art is, not only methods and results, but also the journey of my PhD research.

To capture this journey, I cannot think of anyone but my best friend Kalyarat “Farng” Kuropakornpong [@kalyakuropaa]. Drawing is what she has done for as long as we have met at 5 years old. She loves to draw her friends in different manners and occasions. I have had memories of us captured since.

     ||| “Looking forward to record the next chapter of your life”

is what she replied to me after I told her about this project. She is now a tea master and graphic designer in Thailand.

Another bff who will also be a part of this project is Kochamon “Ja-eh” Kanjanajan [@kettomotto]. Ja-eh is a software developer who has videography as a hobby. She just moves to Dubai and has started her own YouTube channel “Kate and Pat in Dubai”. She will record the journey of my research and Farng’s art in her prospective.

We are so excited to work together on this project and curious about what we will build together. Stay tuned for the next update 0f Enhancer in Art: The journey of Natsuda’s PhD with us !!!

Natsuda N    x    kalyakuropa    x    kettomotto

 

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NanoBioTech-Montreux, Switzerland (15-17 November 2021)

The goal of this conference was to present my results achieved with the Elveflow droplet microfluidic platform through my poster contribution and discuss potential applications with other researchers of the nanobiotechnological field, thereby further building my professional network in addition to that.

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NanoBioTech-Montreux, Switzerland (15-17 November 2021)

The goal of this conference was to present my results achieved with the Elveflow droplet microfluidic platform through my poster contribution and discuss potential applications with other researchers of the nanobiotechnological field, thereby further building my professional network in addition to that.

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Blog 1: My EIA Expectations

Being part of the Enhpathy consortium allows me, as well as all the other Enhpathy students, to team up with an artist. The idea is to introduce him/her to our project and participate in the creation of an artistic version of our research. Here, in this blog series I will share my personal progress and experiences on the Enhancer in Art project.

The intriguing combination of Art and Science

In recent years I have heard about many projects that aim to combine science and art. For instance, during my university studies I learned about the ‘dance your PhD‘ competition from the Science journal. For that PhD students record a short video of them dancing their projects. This is not only highly entertaining (i.e., dancing scientists) but also offered an alternative way for me to discover other research projects, I would have probably never heard about otherwise. I was hence thrilled that bringing together art and science is part of the Enhpathy program with the ‘Enhancer in Art’ initiative.

My Expectations

For me there are two main expectations for the Enhancer in Art project:

On the one hand, I am looking forward to learning more about science communication. As a researcher I often find myself being part of a science bubble. Of course, I have many opportunities to present my work, at conferences, meetings, in a publication and so on. Most of these events are however limited to researchers. Yet, we have come a long way from limiting science to a small group of men working on secret projects in their basements. On the contrary, many (non-science involved) people have become more and more interested in knowing about the developments on the forefront of science. We as researchers certainly have the responsibility to communicate our work. I hope that with the EIA I can practice and learn how to talk about my project to non-scientist. This will, without doubt, provide me with a skill, I would largely benefit from in my future career.

On the other hand, I aspire to get attention and excitement for my PhD project from a non-scientific audience. I intend to emphasize the importance of the work we as scientists and as a consortium are doing. I hope that by working together with an artist I will reach a broad audience. After all what better way to convey a message than through art?

Even though the EIA is outside of my normal science comfort zone, I am very excited about getting this part of the project started and hope to soon to be able to give an update on it.

 

 

 

 

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MicroTAS 2021, Palm Springs, California, USA (10-14 October 2021)

As MicroTAS is one of the major international conferences in the microfluidics field, the objective was to connect with other researchers working on similar projects to build an international network that I could benefit from. With my poster, I presented the preliminary results of my single-nuclei ATAC-sequencing project with the aim of receiving feedback and input on this project.

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The EMBO workshop starts today

The new  EMBO workshop co-organized by Álvaro Rada-Iglesias, Salvatore Spicuglia and Susanne Mandrup and involving 6 Enhpathy’s students starts today. Please find more information about this event on the EMBO Workshop’s website.

About the Workshop

Due to the current COVID-19 emergency this workshop might need to be cancelled depending on national and local recommendations. In order to give both organizers and participants more time before making any decision, the registration and payment deadlines have been extended. In case of cancellation, registration fees will be reimbursed. We also recommend all invited speakers and participants to purchase their flight tickets with a cancellation insurance

Mutations within coding genes have traditionally been considered the major genetic cause of human disease. However, it is becoming increasingly clear that the genetic, structural and/or epigenetic disruption of enhancers represent major etiological factors in numerous human diseases (i.e. enhanceropathies), ranging from rare congenital disorders to common diseases associated with ageing and lifestyle (e.g. cancer, diabetes). Although changes in enhancer activity are predicted to have broad pathological and therapeutic implications, we currently have a limited understanding of human enhanceropathies. This reflects, at least partly, our still primitive and partial understanding of the mechanisms whereby enhancers can control gene expression. To overcome these limitations, this workshop will bring together experts in enhancer biology, gene regulation and medical genetics that, during three days, will present their latest work. Our invited speakers and participants will discuss the multidisciplinary approaches required to investigate enhancer function as well as debate about the role of enhancers in fundamental biological processes (e.g. embryonic development, evolution) and in the etiology of human disorders. Ultimately, the goal of this EMBO Workshop will be to provide a complete view of how a deep and systems-level understanding of enhancer function can facilitate elucidating the molecular basis of human enhanceropathies.

 

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Enhancers in Art; Post I

 

At the Copenhagen event, I got the opportunity to meet all involved with ENHPATHY, which was a real pleasure.

Among the scientific discussions and lessons, we also spoke about our Enhancer in Art projects.

A defining characteristic of art (I think) is that a piece of art is supposed to provoke thought, or at the very least kindle the imagination. Science, at its core, is aimed at understanding the world around us (or inside us). It seems to me thus that science and art are two different entities when we consider their ‘purpose’.

However, that is not to say that they have nothing in common. For example, to reach the goal of ‘understanding’ the world around us, what is required is thought, and in many cases creativity. In the way that a piece of art may induce serious thought and reflection in a patron such that they start to view an issue in a different way – in this same way can issues be tacked in science.

I will be lazy here and refer to the very famous ‘double slit’ experiment done by Young in 1801, which, together with many efforts from scientists over the globe and across decades, gave rise to quantum mechanics. The point is that the outcome of the experiment (the pattern in the photo) was the same for light, which was thought to be composed purely of waves, and for electrons, which were thought to be particles. This then lead to a lot of thought, and the ultimate conclusion that matter has properties of both waves and particles.

 

I will provide an update on my Enhancer in art project in the next post!

Pictured below is my poster which was displayed at the Copenhagen event, along with its owner. Thanks to Jean-Mehdi for the photograph!

featured image taken from https://ysjournal.com/double-slit-experiment-using-arduino-and-light-sensors/

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GDR Micro-Nano-Fluidics, Toulouse, France (23-24 September 2021)

The purpose of visiting this conference was to present my poster providing an outlook on my project involving multiwise chromatin interaction analysis using our Elveflow droplet microfluidic platform and gain input on my approach to this project. Further, the idea was to network with the French microfluidics community.

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Enhancer in Art: a exploratory way of science dissemination to public

Popular science plays a very important role in scientific research. Not only attracting people to know what we are doing, but also motivating ourselves to thinking the significance of our research.

Recently, I faced a challenge about how to introduce my project to a 13 years old boy with no biology learning experience. I tried my best to let him know what is enhancer, why we research enhancer and how it can influence human health. The boy didn’t show interesting for my projects, excepting a picture instance I showed about mutation in enhancer influences human finger development.

           

          Visel et al. Nature, 2009.                                        Jeff Koons’ exposition in Mucem

It reminded me science in art format maybe impress people better if we find a good way. But how to link my research and art? And what is art? Occasionally, an exposition visiting experience in the Europe and Mediterranean Civilization Museum of Marseille made me understand art differently. It’s an art exposition of Jeff Koons, who is a very famous modern pop artist in the world. As a zero-level person in art, I was confused when I looking at Jeff Koons’ art works. Because many of his art works look like very common daily life product. A student who study in art explained to me, “Art could be anything. According to visiting an exposition of artist, you can know who is him, what is his story, what do he want to say. Sometimes art attracts people and becoming popular. Sometimes art shocks people and full of controversy. That is art! Always brings new idea and lead people to think”.

It opened my mind to art somehow. I’m still thinking how to coincidence my research with art. But cooperating with artist must be very interesting and exciting. We can provide materials and inspirit for artist. One tube of DNA or one DNA sequence also could be art source for them. And artists create art works attracting more attention from people to science research, even leading us to think the deep and far significance and influence of our research in the future.

As a part of ENHPATHY network program, Enhancer in Art is a novel and challenging work to introduce our work to outside world. I’m looking forward to linking enhancer study with art creating!

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1 PhD position available, join the ENHPATHY Innovative Training Network today!

One position is available for a 2-year PhD program funded by the Marie Sklodowska-Curie Innovative Training Network (ITN) ENHPATHY.

Candidates with bioinformatics, genomics and/or molecular and cellular biology backgrounds are encouraged to apply. The host lab offers opportunities to extend this period for one or two years to complete a full PhD thesis in the Centre for Genomics Regulation and Universitat Pompeu Fabra.

Application deadline: September 30th

Organization: Centre for genomic regulation

More information on this link 

Download the full description

 

 

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Starting my PhD!

 

Hello everyone! Thank you for the warm welcoming from all the members from the amazing ENPATHY consortium!

This is, my very first blog post (ever).

Our lab, the lab46

You might have read my introduction, where I wrote about how I have been moving around for most of my life. Finally, I have truly found my place, in the group of Hematooncology at the institute of molecular genetics (IMG), in Prague, led by Meritxell Alberich Jorda (Or as we call her, Meri). By the way, the picture featuring this post, is the logo of our group. It was designed by Maria Kuzmina, one of the PhDs in our team.

How would I describe the lab 46? Well, we have the kind of people that, without doubting and as many times as necessary, will help you with anything that you will need. Moreover, I feel that we all really support each other, not only when it comes to experimental questions. This group is comprised the kind of people that will make pancakes when you have to wake up at 5 in the morning for an experiment, or that will bring champagne to thank you for the support through a hard time. That will make sure your birthday is something special even when it falls on a Monday full of work. That will text you to check if you are okay after a hard day at work.

I think, that within us and thanks to Meri, we have created a perfect research microenvironment. And I am looking forward to expand it, thanks to the wonderful opportunities that ENPATHY consortium gives us.

Our project, HSCs under Chronic Inflammation – the CMO mouse model

You might have also read a bit about my project. Maybe even our recent publication by Grusanovic et al. If not, here you have the link! I promise you will like it   (nih.gov)https://pubmed.ncbi.nlm.nih.gov/36341527/

Here we have shown, how chronic inflammation decreases HSC fitness via hyperactivation of the druggable IL-6/Jak/Stat3 signaling pathway, and how the CMO model accurately recapitulates sterile chronic inflammation.

There are two things to highlight about this mouse model. The first one, is that it contains a point mutation in the Pstpip2 gene, causing Chronic Multifocal Osteomyelitis (CMO). The second, that this model resembles a human disease know as chronic recurrent multifocal osteomyelitis (CRMO), a progressive autoinflammatory disorder that leads to sterile chronic inflammation.

Using the CMO murine model we were able to bypass the artificial setup of externally inducing inflammation. This allowed us to assess the interactions of an inflammatory BM niche, immune cells and HSCs.

Effects of chronic inflammation in AML progression

Previously, we have reported that the chronic inflammatory environment expands the HSC compartment and induces functional defects in HSC. There are many similarities between HSCs and leukemic stem cells (LSCs). Therefore, will now characterize the effects of chronic inflammation in Acute Myeloid Leukemia (AML). If you would like to know a bit more about AML, read this: Uncovering drug-adaptive epigenetic response in Acute Myeloid Leukaemia (AML) – ENHPATHY Francesco Leonetti has a wonderful blog post about it!

In my project, we would like to determine how chronic inflammation might influence LSCs, and thus alter Leukemia development. Moreover, we will explore the possible role that chronic inflammation has in the deregulation of enhancers in certain (critical) genes. With this, we will gain more mechanistic insight of the correlation between chronic inflammation and Leukemia development.

The results of this project will contribute to a better understanding of the mechanism driving  chronic inflammation and AML.

I will keep you updated about the process!

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CC BY María Mariner Fauli

All Eyes On Enhancers

My name is Sarah, I obtained my bachelor and master’s degrees in Molecular and Cellular Biology from the University of Rennes 1, France. During my last year of studies, I had the opportunity to work in the laboratory of Alvaro Rada-Iglesias, my actual supervisor. It was a wonderful experience; I had the chance to discover a new country and new people. I also discovered what is like to work in a laboratory and get my hands into more concrete biological questions.

A week in research is never the same.

It can be challenging and frustrating. Hard work, long hours in the cell culture room, fails… All this become worthy whenever I get new progresses in my project. In this blog, I will try to share my advances, new concept, and techniques I will learn during my PhD journey.

A day spend in the laboratory is not only about experiments and work but also about the people we get to meet and exchange with. I have the fantastic chance to share the lab with Spanish and international people. If you walk around in the lab, you will have great chance to hear all about Greek etymology, or me asking for Pastéis de nata to our great Portuguese post-doc in the lab.

I am really proud to be part of the ENHPATHY network, that will raise intriguing and relevant questions about enhancers, their functions, mechanisms and relevance in human diseases.

I want to thank the ENHPATHY consortium for this challenge and to offer me a space where to share my thoughts. My future self will with no doubt be thankful to find a trace of the baby researcher that I am today.

Joining the Rada-Iglesias laboratory.

I have the opportunity to work on the interplay between gene expression control and exposure to environmental factors and how it might contribute to human disease. More specifically, my project focuses on unravel potential gene-environmental interactions involved in the etiology of ZIC2-related holoprosencephaly.

Holoprosencephaly (HPE) is a developmental disorder that affects the early development of the brain and is characterized by the failure of the separation of the two hemispheres; ZIC2 is a member of the ZIC family and encodes a zinc finger transcription factor that, when mutated causes HPE in both, mouse and human.

Intriguingly, humans but not mice are haploinsufficient for ZIC2. In addition, patients carrying the ZIC2+/- genotype show different level of severity of the disease and reduced penetrance. How can these differences be explained? Rather than a specie differences, we hypothesize that because mice live and reproduce in the laboratory in well-controlled conditions and humans live in a non-controlled environment, environmental factors could explain, at least partially, the haploinsufficiency observed in patients carrying ZIC2+/- genotype.

To tackle this question, I will implement a work plan combining genetic engineering, culture of mouse and human embryonic stem cells, genomics approaches… I will be happy to share my advances in the next posts!

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All Eyes on NN’hancers : Greeting

 

This is my very first blogging !!!

        Hi from Copenhagen, Denmark! My name is Natsuda Navamajiti, a PhD fellow at University of Copenhagen (also known in Danish as København Universitet), under the supervision of Prof.Robin Andersson. I am a part of ENHPATHY project (Link to the program here) which basically gathers supervisors and PhD fellows in both academia and industry who are interested in specific part of DNA called “ENHANCER.” 

“Stay tune on my blog, 
and also on people-in-the-program’s, 
to know more about what the enhancer is 
and our projects related to the enhancer!”

        My own project will be related to a blood disease called acute myeloid leukemia (AML) in children. Regulatory activities of enhancers and promoters in blood cells will be mainly explored using techniques called CAGE and ATAC-seq. Computational methods will be a key part in investigating how these can be used to understand clinical data such as disease subtypes or prognosis.I will write more about these interesting techniques in the upcoming blog. 

        It has been 6 months since I arrived here, just before the lock-down period due to the corona crisis. Even though it is not so lively as usual, Copenhagen is still charming. Can’t wait to explore the full version of this “City of Hygge” soon. 

        Inspired by Mickey Mouse Lego Art I am ensemble right now, 

“Miska Mouska Mickey Mouse, 
Welcome to My Blog!”

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Uncovering drug-adaptive epigenetic response in Acute Myeloid Leukaemia (AML)

I am very grateful to ENHPATHY consortium for giving me the opportunity to be part of this PhD project.

 

In my view, it is fascinating to understand how further genetic regulation may occur through chemotherapeutic drug stimuli that can increase the activity of specific enhancers.

In my PhD project I will be involved in studying genetic adaptations taking place after exposure to standard-of-care drug and their association to resistance in acute myeloid leukaemia (AML).

 

The AML is the most common acute leukaemia in adults. The disease is characterized by an uncontrolled clonal proliferation of undifferentiated myeloid precursor cells in the bone marrow and usually their presence in peripheral blood.

With a median age of 68, the World Health Organization (WHO) system divides AML into several groups:

  • AML with recurrent abnormalities;
  • AML with myelodysplasia-related changes;
  • therapy-related AML;
  • AML not otherwise specified.

Although the discovery of the most recurrent genetic mutations (i.e. FLT3-ITD, NMP1 and CEBPA) has certainly helped to provide better treatment support, to date the standard of care remains the intensive chemotherapy treatment with anthracyclines and aracytidine but with poor results. Indeed, responses are not durable, and majority of patients relapse with acquired drug resistance and die from the disease afterwards.
AML remains a clinical challenge and both a better understanding of the resistance mechanism and new therapies are urgently needed.

 

Doubtless drug resistance is related to the gravity of genetic mutations underlying AML, but it is also related to the alterations in the epigenetic regulation of proximal promoters and distal enhancers. In this field, a better understanding of the epigenetic regulation underlying resistance to chemotherapy treatment in AML could respond to the need for new therapies.

Accordingly, the main aim of this project is to study regulatory elements that are directly targeted by anticancer drugs in order to analyze in depth associated with drug resistance.

 

The human ALDH gene superfamily consists of 19 isoforms from 19 genes in 11 families and four subfamilies. Physiologically, the major function of ALDH enzymes is cellular detoxification via the NAD(P)H-dependent oxidation of toxic aldehydes into carboxylic acids. Aldehydes are produced naturally as by-products of the metabolism of glucose, amino acids and lipids, but also may come from exogenous sources like exposure to chemicals, including chemotherapeutic agents.  Importantly, the oxidation of aldehydes is not the only catalytic function of ALDHs. Some members of the superfamily are known to have esterase or nitrate reductase activity and other various functions notably in cell differentiation and cell signalling.

Consequently, in cancer cells, where metabolic demands are elevated, and/or genetic mutations lead to an aberrant metabolism, the formation of endogenous toxic aldehydes is often exacerbated. In this contest, ALDH may represent a key survival adaptation and a marker of malignancy.

In particular, the ALDH subfamily 1A is associated with tumor progression and refractoriness and are elevated in multiple cancer types. These isoenzymes have been widely associated to poor prognosis, high tumorigenic potential and drug resistance.

In the context of AML, multiple studies suggest that ALDH1A1 is strikingly associated with drug resistance and increased risk of relapse.

 

Recent progress achieved by Advanced BioDesign (ABD) have shown that higher ALDH1 activity is characteristic of leukemic cells in refractory patients and in patients with adverse prognosis. More so, using different AML cells lines, they have found that certain chemotherapeutic drugs can modulate gene expression of at least three closely related isoforms of the ALDH family associated to drug resistance, thus supporting the idea of this project.

Currently, ABD develops specific inhibitors against ALDHs. The anticancer activity of these compounds has been demonstrated in prostate, non-small cell lung cancer and melanoma and more recently in preclinical models of AML.

 

The specific objectives of our project are:

  • To map enhancer or promoter regions that are disturbed in AML and normal hematopoietic cells during anticancer drug exposure (namely, Daunorubicin, DIMATE and Ara-C) and identify their putative target genes.
  • To characterise the role that the identified regulatory regions have in drug resistance.
  • To assess the ability of the most prominent factors to sensitize or re-sensitize AML cells to undergo programmed cell death.

We expect to:

  • identify the drug-responsive regulatory elements directly responsible for the severity of AML and their drug resistance traits;
  • discover rational strategies with improved therapeutic efficacies by targeting enhancers with inhibitors that can modulate the transcription of the genes linked to drug resistance.

 

I hope you enjoy my blog, and I am looking forward to sharing with you my first results.

 

Francesco.

 

 

 

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Enhancers

It has become apparent to me that computational biology as a field is vast. It can prove to be very quantitative, and methods and approaches used are susceptible to increasing levels of abstraction. Much of this is a by-product of the advent of Next-Generation Sequencing methods, which are able to generate large amounts of data.

The regulation of gene expression is a complex process involving many factors. It can be seen as the product of the interaction between the DNA sequence itself with proteins, protein networks, RNA, and the so-called regulatory elements – which are segments of the DNA sequence that are functional, in that they interact with, or recruit other factors which facilitate the next steps in the process. I think it is easy to appreciate the elegance of the process as we know it, as well as the fine balance of factors and the internal environment that surely must be maintained for the optimal functioning of such machinery.

I have learnt, thanks to the ENHPATHY consortium, that enhancers are one such regulatory element that are more important than previously thought, having been implicated in many regulatory networks, and therefore in many diseases. I find myself keen to uncover more about their influence over the gene regulation and, in this way, the body itself. I am fortunate to be a part of a motivated group of peers and senior researchers alike, whose research and progress I plan to follow with interest. I hope to share more with you soon!

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Science and art: the fusion of two universes

The picture linked to this article has not been chosen by chance. The “Vitruvian Man“ by Leonardo da Vinci perhaps represents one of the first encounters between science and art.
In this drawing, the great artist-scientist represents how the union between science and art is possible by placing the figure of a man symmetrically within geometric spaces defined as the circle and the square, respectively, Heaven and Earth.

Although the science-art partnership has its roots centuries ago, nowadays science does not enjoy the same understanding as art and it is seen by most as something mysterious.

Seen this, I wondered why.

It is a fact that science is a hard subject to understand, especially for the large number of concepts not owned by common people which cannot be found among the general knowledges of a country.

Well, actually I think that the “Enhancer in Art” (EIA) project within the ENHPATHY program can be a way to bring people closer to science, taking off that mystery dress it wears for common people. Making science more “popular” in its understanding could also increase people’s interest in it.

Plus, the EIA project will be a way to test us as young researchers.

Not by chance, the first difficult purpose will be to make our project and our research understandable to the artist who will follow us, using a language that is not as much scientific as direct. That is why, we would try to address him as friends, turning scientific language into a friendly conversation.

One of the articles I have recently read about science-art partnership published in Nature states that the collaboration between scientists and artists is the most valuable when these “have a shared stake in a project” which can help the scientist so much in stimulating new research work as much as the artist in creating something unique also leading to new career opportunities as desired by Virginia Gewin.

So, what do I expect from this project? My greatest goal is to try to get people feel what we, young researchers, feel about science and scientific research. The feeling, the emotion, the pride that we feel in contributing to the knowledge of a specific topic, hoping that it will be useful to the community.

And in this sense, I feel lucky to be able to tackle the EIA project in Marseille, a city with a deep sense of art, as it was the European capital of culture in 2013, which boasts a multitude of young local artists.

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Millefiori by Fabian OefnerFabian Oefner

Art vs Mystery of Science

We live in the era of technological advancement where scientific contribution is the primary driving force of progress. Despite a rapid decrease in the distance between the achievements of science and their implementation in our daily life, it is still a widespread opinion that research is separated from reality and that scientists live in their own universe. To overcome this prejudice and fear of science, and to increase the general public’s willingness to trust and accept inventions, we have to find ways of efficient communication between scientists and society.

During my undergraduate studies, I was learning some abstract concepts in pure mathematics, so later on, when I started studying computational biology, I thought, “Wow! Now I am finally engaged in solving applied problems!”. The application of mathematics in the interdisciplinary field of Life Sciences fascinates me. And perhaps results of my future research could be used to either improve our understanding of diseases, or facilitate the creation of a new drug, or invent a new therapy. Who knows, right?

And while science is fascinating to us researchers, in a non-academic environment, the word “science” is often surrounded by mystery. It is associated with something distant and incomprehensible. This “fear” of science has a negative impact on society as it weakens the general credibility of scientific discoveries. This, of course, slows down the progress because new technologies’ success depends a lot on the public’s willingness to accept them. We, researchers, can help to reduce the general level of anxiety towards science by making it more inclusive and sharing our knowledge in an understandable form.

Lately, the concept of Open Science has started attracting significant attention from the scientific community, especially in applied fields. This movement aims not only to make research reproducible and accessible but also understandable to everyone, regardless of a person’s educational background. The more I dive into various scientific activities, the more I understand why it is crucial to efficiently communicate and disseminate science. News from the scientific world have to sound less like magic spells but more like intriguing stories*. How can we bridge this gap?

Art, being the universal language of emotions and senses, can serve as a mean of communication between scientists and the rest of the world. Perhaps, the ideas coming from science are easier to understand not logically but through emotions? At first glance, it may seem that science and art are absolutely incompatible. However, if you think about it, these two worlds — both abstract and creative — have a lot in common! They aim at exploring new horizons, providing another perspective on already existing things, and communicating this position to others. Moreover, scientists are often artists as well! A number of great inventors and scientists of the past — such as Leonardo da Vinci, Mikhail Lomonosov, Lewis Carroll, and many others — are known for their works of both scientific and cultural value.

From our side, we can contribute to the creation of things emerging on the edge of the two so different but at the same time so similar worlds. Within the ENHPATHY consortium, there is a program called Enhancer in Art that aims at communicating science (in particular genomics) to the general audience with the help of artists. I will soon contact an artist and tell her about my research. I expect it to be challenging mainly because of the need to “translate” some of the terms and concepts we use in our work to tell a fascinating and understandable story. My research focuses on studying the impact of gene regulatory variation on disease utilizing the concept of Variable Chromatin Modules (VCMs). I hope that in the final artwork, we could show the dynamic nature of the VCMs and the complexity of our genome organization.

 

* One of the examples that I find absolutely adorable is the series of coloring and comic books created by the Cell Press team: “Coloring with Cell” and “Color-In Comics: Neurons at Play”!

 

Photo credit: Millefiori by Fabian Oefner

https://fabianoefner.com

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The Art-Science Kinship

The estrangement of artists and scientists appears to have been a feature of ancient civilisation even before the time of Plato, who deduces that poets are imitators of the world, and therefore far from the truth: “the tragic poet is an imitator, and therefore, like all other imitators, he is thrice removed from the king and the truth.”Even now, the opinion is very widely prevalent that art and science are in some sense mutually antagonistic, where one is considered closer to truth and the other an artefact of one’s imagination. Though there are people who would repudiate such an opinion but, even amongst them, there seems to be very little feeling of any need to establish their essential harmony. In such times, the Enhancer in Art (EIA) initiative by the ENHPATHY program stand unfazed by the criticism and determined to compose an exemplar for the budding scientific art community.

Art and Science

Amongst the most celebrated instances in history of intertwining of art and science, nothing stands closer to that of Marianne North and Charles Darwin in my opinion. Born in Hastings, England, Marianne North was a Victorian plant hunter and prolific botanical painter. She played a key role in botanising, and in the transfer of botanical knowledge, not only as illustrators of the physical characteristics of botanical subjects but also in advancing the ways that scientists (in this case study, those that study plant sciences at Kew) have understood, named, represented, categorised and related to plants. Around the same time, Charles Darwin was studying phenomena like ‘pleasures of pseudocopulation’ in The Power of Movement in Plants, which was believed to be induced by the enticing colours of orchids. Later, she was invited to Australia in 1880, on the recommendation of Darwin to paint their extraordinary flora. Charles Darwin was an avid supporter and considered North’s paintings to be excellent examples of his theory of nature.

Art and ENHPATHY

Continuing the legacy of Marianne North, Charles Darwin and many more, ENHPATHY has created a platform for knowledge dissemination and public engagement in the field of enhancers and associated diseases by the medium of art. In my view, the research community is constricted and often requires a certain level of scientific acumen as a premise to step into. Collaborating with a local artist, I would be able to covert my research of complex biological phenomena to intelligible concepts, bypassing the gatekeepers of the scientific community and reaching out to the general public.

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Functional assay of regulatory elements could aid early detection of Congenital Heart Defects (CHD)

In the world of scientific investigations and innovative research, biomedical research offers a great many opportunities to contribute to improving both longevity and quality of life. An educational background in computer science and numerical computing intertwined with bioinformatics made me more conscious of the importance of the ENHPATHY initiative. ENHPATHY is not only an excellent research endeavour but also a significant step towards the humanitarian cause. During my stay in the UK, I was heavily involved in the COVID research on cancer patients with UK Coronavirus Cancer Monitoring Project (UKCCMP), which further motivated me to work towards health science and genetics-based research.

Congenital heart defects 

Congenital heart defects (CHD) are a varied group of structural and functional disorders that occur in the developing heart of neonates and children. CHD is the leading cause of infant morbidity and is prevalent in about 1-3% of all live newborns. Routine clinical diagnosis of CHD is often performed prenatally to examine the heart structure for defects in the walls, valves, and vessels. Surgical intervention and therapeutic management techniques for CHD have improved significantly over the last few decades and an early diagnosis and subsequent treatment have the potential to drastically improve perinatal outcomes. However, studies have found that a number of these CHD diagnoses are missed in the birthing clinic and thus infants are later diagnosed upon hospital admission for critical symptoms such as cardiac shock.

The advent of next-generation sequencing made prenatal genetic diagnosis possible. However, the underlying genetic architecture suggested that the causal CHD variants were found to be those identified on a family-by-family basis rather than identified statistically at a population level with GWAS (Genome-Wide Association Study). In conclusion, the theory of CHD aetiology became that many common variants, as detected by GWAS, add to the risk of CHD, but these exist alongside rare variants which carry a much higher contribution. Therefore, an unbiased whole-exome sequencing (WES) approach started to be utilized to identify rare causal sequence variants in familial or sporadic CHD cases. Unfortunately, due to poor diagnostic success rates of both CHD gene panels and WES, along with the limited genome-wide coverage of both methods, the focus is now turning to whole-genome sequencing (WGS) to investigate whether non-coding sequence variants can lead to an improved diagnostic yield for CHD.

Introducing SuRE and its potential role in new CHD variants identification

However, identification of variants is just the first step, major challenges lie within identifying causal variants amongst them. Due to the intricate spatial-temporal regulation of transcription-factor binding to non-coding cis-regulatory elements, the functional effect of these variants is not predictable just from the sequence. Functional assays are commonly employed alongside WGS to determine whether a variant has a functionally significant effect on gene expression. Survey of Regulatory Elements (SuRE) is a massively parallel reporter assay platform that can identify and assay novel promoters/enhancers at high throughput. Additionally, SuRE can assay CRE activity in any transfectable cell line and previous applications have found differing cell types to have unique regulatory profiles. We hypothesize that using SuRE technology, we would be able to detect some of these causal variants while establishing a database with millions of non-coding sequence variants – all functionally annotated for their effect on enhancer and promoter activity in several disease-relevant cell types. This database of non-coding sequence variants and causal variants would not only be a major accomplishment of the project but also an important resource for strategies aiming to link genotypes to phenotypes like the GWAS and eQTL (Expression Quantitative Trait Loci) studies.

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EMBO workshop, October 6-9, 2021 | Santander Spain

The new  EMBO workshop co-organized by Álvaro Rada-Iglesias, Salvatore Spicuglia and Susanne Mandrup is now open for registration –> register here. 

About the Workshop

Due to the current COVID-19 emergency this workshop might need to be cancelled depending on national and local recommendations. In order to give both organizers and participants more time before making any decision, the registration and payment deadlines have been extended. In case of cancellation, registration fees will be reimbursed. We also recommend all invited speakers and participants to purchase their flight tickets with a cancellation insurance

Mutations within coding genes have traditionally been considered the major genetic cause of human disease. However, it is becoming increasingly clear that the genetic, structural and/or epigenetic disruption of enhancers represent major etiological factors in numerous human diseases (i.e. enhanceropathies), ranging from rare congenital disorders to common diseases associated with ageing and lifestyle (e.g. cancer, diabetes). Although changes in enhancer activity are predicted to have broad pathological and therapeutic implications, we currently have a limited understanding of human enhanceropathies. This reflects, at least partly, our still primitive and partial understanding of the mechanisms whereby enhancers can control gene expression. To overcome these limitations, this workshop will bring together experts in enhancer biology, gene regulation and medical genetics that, during three days, will present their latest work. Our invited speakers and participants will discuss the multidisciplinary approaches required to investigate enhancer function as well as debate about the role of enhancers in fundamental biological processes (e.g. embryonic development, evolution) and in the etiology of human disorders. Ultimately, the goal of this EMBO Workshop will be to provide a complete view of how a deep and systems-level understanding of enhancer function can facilitate elucidating the molecular basis of human enhanceropathies.

 

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Supervisors

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COORDINATION BOARD

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INFOS ESRs

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Marie CurieThis project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 860002. The information contained in this website reflects only the authors’ view. REA and EC are not responsible for any use that may be made of this information.