symposium – EMBL Events

Best Poster Awards – Metabolism Meets Epigenetics

In its first edition, the EMBO|EMBL Symposium: Metabolism Meets Epigenetics brought together 289 world-leading researchers who examined how metabolites and metabolic networks impact gene regulation, what their roles are in disease and how this opens novel therapeutic avenues.

In addition to the 21 invited speakers and 22 selected short talks, 142 posters were presented during the two poster sessions. Today we present three of the five award-winning posters decided by popular vote.

Citrate carrier links intermediate metabolism to histone acetylation upon ageing of mouse mesenchymal stem cells (MSCs)

Authors: Andromachi Pouikli (1), Monika Maleszewska (2), Swati Parekh (1), Chrysa Nikopoulou (1), Maarouf Baghdadi (1), Linda Partridge (1), Peter Tessarz (1)

Chromatin and metabolism interact in a reciprocal manner; on one hand metabolism-related genes are subjected to epigenetic modifications, which regulate gene expression. On the other hand, intracellular metabolism provides metabolites which can serve as essential co-factors and substrates for chromatin-modifying enzymes, affecting their activity. Although, it is well established that the process of ageing is accompanied by changes in metabolism and by chromatin alterations, their interplay in this context remains still poorly understood. In this study we sought to determine how ageing impinges on the relationship between cellular metabolism and the epigenome, using mouse mesenchymal stem cells from the bone marrow (BM-MSCs). In brief, our data suggest that there is a strong and direct link between the metabolic and the epigenetic states of the cell, with ageing-driven changes in metabolism regulating gene transcription and BM-MSC’s stemness, via alterations of the chromatin structure. We conclude that physiological ageing elicits changes in metabolism, resulting in suppressed glycolysis and impaired lipid biogenesis. Moreover, we demonstrate that during ageing there are lower levels of histone acetylation, despite the higher acetyl-CoA levels. We provide a solid explanation for this apparent discrepancy, pointing to the impaired export of acetyl-CoA from mitochondria to the cytosol. Indeed, the protein levels of the citrate carrier Slc25a1 decrease dramatically upon ageing. Using inhibition and supplementation experiments we provide a causal relationship between Slc25a1 function and the levels of histone acetylation, which directly influence chromatin accessibility and plasticity. Collectively, our data establish a tight, age-dependent connection between metabolism, epigenome and stemness and identify citrate carrier as the responsible protein for the mitochondrial-nuclear communication.

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(1) Max Planck Institute for Biology of Ageing, Germany, (2) Personalis Inc, Germany

Epigenetics meets metabolism through histone acetyltransferase NAA40

Authors: Christina Demetriadou (1), Anastasia Raoukka (1), Agathi Elpidoforou (1), Constantine Mylonas (2), Swati Parekh (2), Peter Tessarz (2), Antonis Kirmizis (1)

N-alpha-acetyltransferase 40 (NAA40) is distinct among other histone acetyltransferases (HATs) because it deposits an acetyl moiety on the alpha-amino group at the very N-terminal tip of histones H4 and H2A, instead on the lysine side chain. The biological function of this evolutionarily conserved enzyme remained unexplored for several decades because it was thought to mediate an inert modification. However, we previously showed that NAA40-mediated N-terminal acetylation of histone H4 (N-acH4) crosstalks with an adjacent arginine methylation mark to regulate yeast cellular aging in response to caloric restriction through transcriptional control of several metabolic genes. Therefore, we are currently interested in deciphering the function of human NAA40 in carcinogenesis. We recently showed that NAA40 is frequently upregulated in primary human colorectal cancer (CRC) samples. Remarkably, depletion of NAA40 and its accompanied reduction in N-acH4 blocked colon cancer cell proliferation and reduced cell survival in vitro and in xenograft models. We also found that loss of NAA40 expression or of its HAT activity markedly induce global histone methylation. Additionally, whole transcriptome analysis showed that NAA40 knockdown leads to upregulation of key enzymes involved in one-carbon metabolism. Intriguingly, silencing of methylenetetrahydrofolate reductase (MTHFR), which links the folate to methionine cycle, rescues the induction of global histone methylation and loss of cell viability triggered by NAA40 depletion. Hence, this recent work implies that NAA40 may transcriptionally regulate vital metabolic enzymes to control the flux of carbon units into the methionine cycle influencing S-adenosylmethionine (SAM) levels and triggering epigenome reprogramming of cancer cells. Overall, our findings thus far propose that NAA40 and its associated N-acH4 are crucial epigenetic modulators in tumourigenesis and implicate these factors in rewiring cancer cell metabolism.

Poster currently not available.

(1) University of Cyprus, Cyprus
(2) Max Planck Institute for Biology of Ageing, Germany

Role of MOF acetyl transferase in mitochondrial homeostasis

Authors: Sukanya Guhathakurta (1), Christoph Martensson (2), Alexander Schendzielorz (3), Bettina Warsheid (3), Thomas Becker (2), Asifa Akhtar (1)

Mitochondria lies at the centre of cellular and organismal energy homeostasis, housing a large repertoire of enzymes that are required for the synergy of various metabolic pathways. Mitochondrial gene expression and protein acetylation are two important fundamental processes situated at the crossroad between mitochondrial function and metabolic status of a cell. Gene transcription in the mitochondria has been studied over several decades, but enzymatic acetylation of mitochondria proteins has stayed so far enigmatic. MOF acetyl transferase and its KANSL complex members dually localize to the nucleus and the mitochondria in mouse and human cells. The MOF-KANSL complex regulates metabolic gene transcription in the nucleus and expression of Electron Transport Chain (mtETC) components from the mtDNA, in a cell type dependent fashion. Regulation of nuclear gene transcription by MOF is well understood, however, its control of mitochondrial function remains elusive. Here, we report that loss of MOF leads to severe mitochondrial dysfunction in Mouse Embryonic Fibroblasts (MEFs), sprouting from a stalled oxidative phosphorylation. We address the mechanisms by which the enzyme maintains mitochondrial function in these cells by using a multi-omics approach. We discovered that the role of MOF-KANSL complex in the mitochondria of aerobically respiring cells could be decoupled from its regulation of steady state RNA levels, and could further be attributed to the acetylation of mitochondrial proteins. We characterize the role of acetylation on these proteins through generation of acetylated and non-acetylated mimics. Collectively our data, along with previously published works, suggests that MOF has emerged as a moderator to strike a harmony in the context of communication between the nucleus and the mitochondria. Recent progress on the project will be discussed.

(1) Max Planck Institute for Immunobiology and Epigenetics, Germany
(2) Institute of Biochemistry and Molecular Biology, Germany
(3) Institute for Biology II, Germany

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Generating meaningful images – a report from Seeing is Believing 2019

By event reporters Liz Haynes @actin_crazy and Stephan Daetwyler @Daetwyler_St

Seeing is Believing event reporters Liz Haynes & Stephan Daetwyler, PHOTO: Liz Haynes/Stephan Daetwyler

The field of biology owes some of its most compelling discoveries to careful visual observation. From Van Leeuwenhoek’s use of new microscopes to describe microscopic “animalcules” in the late 1600s, to Ramon y Cajal’s pioneering 19th century work illustrating beautiful and complex neuronal architecture. Images inspire us, help us generate new hypotheses, and shed light into the tiny worlds yet unexplored. Indeed, these observations uniquely help us understand the structures and dynamics of life, something that would not be achievable with approaches like biochemistry alone.

The images are only as valuable as the amount of information that we can deduce from it.

Generating meaningful images, however, is not an easy task. There have always been limits to what we can observe, due to the properties of the sample or the techniques that we can apply to it. These are the boundaries that microscopists seek to push. A successful imaging experiment requires an amenable sample, a contrast agent to reveal the structures of interest, and a microscope that is capable of capturing an image at a relevant scale. Moreover, the images are only as valuable as the amount of information that we can deduce from it. Therefore, image storage, accessibility and analysis are crucial. Each one of these steps offers opportunities for optimisation and new technologies.

Co-organiser Jan Ellenberg opens the Seeing is Believing symposium, PHOTO: Liz Haynes & Stephan Daetwyler

The EMBO | EMBL Symposium “Seeing is Believing: Imaging the Molecular Processes of Life” (9-12 October 2019) presented us with exciting new developments in all of these fields, coupled with a drive to make new progress available as quickly as possible to the community through preprints, open-source initiatives, and resource sharing.

Advances in sample preparation

At the heart of every imaging approach is the sample. Even the best microscope is ineffective with dim or improperly prepared samples. At Seeing is Believing, we saw an emphasis on using expansion of samples to help overcome the resolution limits of microscopy and solve some traditionally difficult problems. In particular, we were impressed with expansion-based approaches to study centriole structure (Paul Guichard, Ultrastructural Expansion Microscopy) and resolve microtubules tightly packed within axons (Lukas C. Kapitein). By far, the biggest emphasis in sample improvement was on the development of new fluorescent probes and biosensors. Kai Johnsson presented design strategies for the improvement of live cell dyes, and introduced new MaP dyes that are SNAP and HALO compatible, and importantly require no wash to clear unbound probe. Periklis Pantazis presented a mechanosensor based on the Piezo1 stretch activated ion channel, allowing users to visualise mechanical stress within a live cell. Atsushi Miyawaki wowed the audience by meeting the challenge to “be better than a firefly” with a new variant of luciferase named AkaBLI, which his lab generated through targeted evolution. This improved luciferase allowed them to visualise neuronal activity within freely behaving mice and marmosets.

Advances in microscopy

New imaging methods on show at Seeing is Believing, PHOTO: EMBL Events

The features of our microscopes directly determine which questions we can address. Seeing is Believing highlighted exciting new development in building cutting-edge microscopy tools. Reto Fiolka presented a novel single-objective light-sheet microscope enabling imaging of live cells in microfluidics devices or 3D environments with 200 nm lateral resolution. Kevin Dean complemented novel light-sheet development by presenting an axially swept light-sheet microscope ideally suited for all clearing techniques that provides an unprecedented field of view enabling whole tissue imaging with sub-micron resolution. With her imaging approach, Alexandra Pacureanu surprised the audience with how X-ray holographic nano-tomography is capable of resolving the fine, dense and complex neuronal circuitry in large tissues or even organism providing a new route to understand how the nervous system processes information.

Nobel Prize winner Stefan Hell spoke on how to attain 1 nm resolution with super-resolution microscopy, PHOTO: Liz Haynes & Stephan Daetwyler

Further impressive advances were presented in fast volumetric imaging (Lars Hufnagel, light field imaging) and high-resolution imaging, e.g. MINFLUX by Stefan Hell, correlative EM imaging by Harald Hess and Lucy Collinson, GI-SIM/LLS-SIM by Dong Li, and 3D-STED deep in a tissue by Joerg Bewersdorf.

Advances in data analysis

All acquired data is meaningless if we cannot extract information from it. At Seeing is Believing, it became obvious how artificial neuronal networks have become important for image analysis. Applications range from segmentation to denoising an image (BGnet, W.E. Moerner and Noise2Void, A. Krull/Florian Jug). Particularly, the convolutional network architecture U-Net has become an important tool. To provide a user-friendly environment to apply those state-of-the art image analysis tools, Anna Kreshuk presented the iLastik platform as an easy to use tool. A new fundamental approach to handle, visualise and process the large amount of data coming from the microscopes was presented by Ivo Sbalzarini. Instead of using pixels to save an image, adaptive particles approximate the image content. Furthermore, Gaudenz Danuser gave a thought-provoking talk on how current perturbation-based approaches in cell biology can mislead us in our analysis. Danuser emphasised that the observed phenotype from a perturbation of a system (e.g. loss of a protein’s function) is not equal to the real function of the gene. For example, cutting a wire from the battery to the electronic board of radio would lead to the “phenotype” loss of sound. However, the function of the wire was simply to provide power to the radio, not to produce sound! As a better perturbation-free alternative, Danuser introduced a concept used in econometrics known as Granger causality.

Advances in biology

All of these new developments culminated in impressive new insights into biological processes. There were many talks on mitochondria and endoplasmic reticulum dynamics revealed by novel live-cell super-resolution techniques. Suliana Manley gave one of the most intriguing of those talks, on modes of asymmetric and symmetric mitochondrial division.

Co-organiser Jennifer Lippincott-Schwartz presents how RNA moves around the cell and is translated at different locations, PHOTO: Liz Haynes & Stephan Daetwyler

Jennifer Lippincott-Schwartz also gave a stunning presentation on how RNA granules can hitch a ride through an ANXA-11 mediated connection to lysosomes, and how ALS associated mutations in ANXA-11 break this connection. Furthermore, an intriguing new mRNA reading frame sensor (Moon and Sun tags) was presented by Sanne Boersma of the Tanenbaum lab to understand stochasticity of mRNA translation.

To conclude, the field of microscopy has grown so much that some may feel we have solved all the theoretical problems, and only engineering challenges are left – hardware improvements, new materials, new engineering solutions. At the closing dinner of the conference, however, Atsushi Miyawaki from RIKEN beautifully summarised how he felt about the future of microscopy, and of Seeing is Believing. Standing in the banquet hall of the Heidelberg Castle, he told us that castles in Japan remain unfinished. This state of incompletion is not due to any fault of the architects, but a feature of beauty, as it was believed that things that were incomplete had room to grow, and that growth is valuable. No matter how high our achievements are in the field of microscopy and image analysis, there will always be unforeseen avenues of growth. Attending Seeing is Believing has hopefully prepared us to follow those avenues, and to share what we find so we may all grow together.

For a more comprehensive summary of all talks presented at Seeing is Believing, and to get links to preprints, publications, and resources, visit our blog at https://seeingbelievingweb.wordpress.com/

Best Poster Awards – EMBO|EMBL Symposium: Systems Genetics: From Genomes to Complex Traits

The first EMBO|EMBL Symposium: Systems Genetics: From Genomes to Complex Traits (29 Sep – 2 Oct 2019) brought together over 150 international researchers to discuss how genetic variation alters molecular mechanisms to cause phenotypic changes amongst individuals, including quantitative traits and human disease.

From the 77 posters that were presented on-site, 3 were selected as the winners after a shortlist round by popular vote, followed by a selection round by the conference organisers.

Resolving noise-control conflict by gene duplication

Michal Chapal is a PhD student in Naama Barkai’s lab at the Weizmann Institute of Science in Israel. PHOTO: Michal Chapal

Authors: Michal Chapal, Sefi Mintzer, Sagie Brodsky, Miri Carmi, Naama Barkai, Weizmann Institute of Science, Israel

Gene duplication promotes adaptive evolution in two principle ways: allowing one duplicate to evolve a new function and resolving adaptive conflicts by splitting ancestral functions between the duplicates. In an apparent departure from both scenarios, low-expressing transcription factor duplicates commonly regulate similar sets of genes and act in overlapping conditions. To examine for possible benefits of such apparently redundant duplicates, we examined the budding yeast duplicated stress regulators Msn2 and Msn4. We show that Msn2,4 indeed function as one unit, inducing the same set of target genes in overlapping conditions, yet this two-factor composition allows its expression to be both environmental-responsive and with low-noise, thereby resolving an adaptive conflict that inherently limits expression of single genes. Our study exemplified a new model for evolution by gene duplication whereby duplicates provide adaptive benefit through cooperation, rather than functional divergence: attaining two-factor dynamics with beneficial properties that cannot be achieved by a single gene.

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Deep learning on single-cell ATAC-seq data to decipher enhancer logic

Ibrahim Taskiran is a PhD student in Stein Aerts’ lab at the VIB & KU Leuven Center for Brain & Disease Research. PHOTO: Ibrahim Taskiran

Authors: Ibrahim Ihsan Taskiran, Liesbeth Minnoye, Carmen Bravo Gonzalez-Blas, Sara Aibar Santos, Gert Hulselmans, Valerie Christiaens, Stein Aerts
KU Leuven – VIB, Belgium

Single-cell ATAC-seq provides new opportunities to study gene regulation in heterogeneous cell populations such as complex tissues or dynamic processes. We recently developed a probabilistic topic modeling approach, called cisTopic, to predict regulatory topics and sets of co-accessible enhancers from scATAC-seq data. Here, we apply deep learning approaches to analyze these sets of co-accessible enhancers, with the goal to predict the spatiotemporal pattern of enhancer accessibility directly from the enhancer sequence. We trained different types of Artificial Neural Networks, including a hybrid model that combines Convolutional and Recurrent Neural Networks. By applying this approach to a cohort of melanoma patient samples and Drosophila eye disc, we show that key transcription factors can be identified from the convolutional filters. In addition, we use the trained model to analyze the motif architecture in enhancers, such as motif combinations and relationship to nucleosome preferences. We furthermore exploit network explaining methods to predict the impact of somatic mutations, using publicly available SNP databases and in-house whole genome sequencing of inbred fly lines. Currently, to validate our models we are testing (mutated) synthetic cell state specific enhancers using massively parallel enhancer reporter assays (MPRA). In conclusion, training deep learning models on single-cell epigenomics data sets has multiple applications to understand the underlying enhancer logic and decipher gene expression programs.

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ROADdt: Regulation network remodeling along disease development trajectories

Celine Sin is a Postdoctoral Fellow in Jörg Menche’s Group at the CeMM Research Center for Molecular Medicine, Austria. PHOTO: Celine Sin

Authors: Celine Sin, Jörg Menche
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Austria

The human body is comprised of over 200 different cell types varying in size, shape, and function. The differentiation and subsequent maintenance of these different phenotypic states are governed by complex gene regulatory networks that dynamically orchestrate the activation and deactivation of genes. Abnormalities in these networks may lead to dysfunctional expression programs, e.g. uncontrolled cell proliferation. In order to understand the conditions resulting in disease, we must understand the underlying gene regulatory networks governing
the gene expression program. As cells move through the differentiation space, the networks that govern gene regulation are remodeled in order to achieve the appropriate gene expression program. While statistical physics and network theory have demonstrated numerous relationships between the structure of networks and the dynamic processes that act on them,
few studies link these mathematically rigorous principles to gene regulatory networks, none at the level of cell-trajectory-states. The overall goal of this project is to understand the fundamental architecture of gene regulatory networks associated with cell differentiation processes in disease. We hypothesize that the gene regulatory networks of different
cell-trajectory-states along the differentiation trajectory – e.g. transitory, branching, or terminal states – are each characterized by distinct structural features. I will present our first steps in this direction, starting from single-cell RNA seq profiles of tumors. Ultimately, we expect that detailed characterization of the gene regulatory networks in these disease processes will reveal basic principles applicable to other diseases and cell developmental processes.

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How does the environment play a role in biodiversity?

Biodiversity – in all its forms and interactions – is the variety of life on Earth. Climate change is exacerbating biodiversity loss, and vice versa. Ahead of the EMBO | EMBL Symposium ‘The Organism and its Environment’ (1–4 March 2020), we talk to Scientific Organiser and EMBL Director General Edith Heard about the impact the environment has on biodiversity and the role of research in solving global challenges.

Does the environment play a large role in the creation of biological diversity?

Biodiversity is the variety of life on Earth. This life, in all its shapes and sizes, occurs in the context of ecosystems: it relies on and interacts with other organisms and the physical environment. Biodiversity represents the collective ‘knowledge learned’ by evolving species over millions of years, about how to survive the vastly varying environmental conditions Earth has and is experiencing. These varying environmental conditions cause natural variations in biodiversity, as well as genetic and epigenetic changes, within and between species over time. Today, scientists are trying to understand the basis of these natural variations, as they will allow us to understand how life evolves.

Fish populations have declined at an alarming rate, and half the world’s shallow water coral reefs have been lost in just 30 years.

But biodiversity is also a measure of the health of any ecosystem. Recent trends in biodiversity loss show very clearly that humans are destroying ecosystems on a massive scale. According to the Director General of the World Wildlife Fund (WWF), increased pollution, deforestation, climate change and other manmade factors have created a “mind-blowing” crisis. The WWF Living Planet Report 2018 (WWF LPR, 2018) also states that freshwater fish populations have declined by more than 80% on average since 1970 and half of the world’s shallow water coral reefs have been lost in the last 30 years (WWF LPR, 2018). Alongside this, deforestation of tropical rainforests means we are currently losing more than 100 species of plants and animals a day (Holley, 2017). In short, human’s influence on the environment greatly impacts biodiversity and we are currently burning the library of life.

How can you determine the effect of the environment on an organism?

The environment can affect an organism in a multitude of ways. The impact can be transient or longer term; within an individual or across generations. The environment can also lead to molecular, cellular, physiological or behavioural changes. For example, the expression of genes in an organism can be influenced by the external environment, such as where the organism develops or factors associated with where it is located. Gene expression could also be influenced by an organism’s internal environment, including hormones or metabolism. Finally, the genome itself – genetic factors that vary between individuals in natural populations – could also influence gene expression.

Research groups at EMBL look at how variety in organisms comes about

Untangling the impact of genetic and environmental variation can be very challenging and for a long time, scientists have tended to focus on minimising variations in the environment in order to understand how changes in genotype affect phenotype. This, alongside the deeply embedded “one genotype = one phenotype” metaphor, has meant that environmentally induced phenotypic variation has been ignored in favour of ‘‘more useful and precise’’ study of genetic polymorphisms. This is despite the fact that from as far back as the early 1900s, scientists have known that the phenotype of an individual depends on the interaction between its genotype and environmental cues! Today, we finally have the power to consider the impact of the environment on phenotype. We can make precise measurements at the molecular, cellular and organism scales in controlled environments that can be varied and we can sequence genomes at the same time.

We can also take human data paired with environmental data – for example in the context of some of EMBL’s research interests such as infectious disease and microbiomes – to understand the quantitative effects of the environment and its influence on human biology. Pioneering projects such as Tara Oceans have also allowed us to research the interactions between organisms and the environment by generating reference data, discovering emergent ecological principles and developing predictions about how ecosystems will be affected by a changing environment. Understanding how organisms exist together and in changing environments is of fundamental importance for our understanding of biological principles and our knowledge of life.

What challenges are currently being faced in this field?

Studying organisms in their environment will become increasingly important.

Understanding the behaviour of individual molecules, cells or whole organisms is already challenging. Understanding how the environment influences an organism – or populations of organisms – represents a whole new scale in complexity. This is an area that I think EMBL could uniquely contribute to in the future. It will be necessary to shift from researching organisms mainly in the laboratory to studying them in their environment. We will also need to ensure the rapid development of technologies and tools to meet these scientific needs. Alongside this, we need new approaches to integrate large, complex data sets and make sense of them. To rise up to this challenge, we need theory. We are now in a unique position to address the dynamics and complexity of living matter across multiple scales and in the context of changing environment. But we need theory to address societal and planetary issues too. We must aim for a rate of scientific discovery that outpaces the rate of calamity such as biodiversity loss, ecosystem degradation, epidemics and climate change.

What can be done to prepare for the future with regard to biological diversity, the organism and its environment?

Research, research and more research! Environmental problems such as the hole in the ozone layer or acid rain were solved by sound scientific approaches. We need to learn from these past scientific and societal successes. Today the ever-increasing numbers of new technologies are allowing us to collect, measure and store data at unprecedented scales. We also need to bring ecologists, zoologists, population geneticists and environmental experts together to address these research questions. Together we can apply cutting-edge technology with rigour, attract new scientific talent and disseminate knowledge to global communities.

What inspired you to organise this symposium?

As a geneticist and epigeneticist, I have explored the intersection between genotype and the environment and how that produces a phenotype. From observing many areas of research – ranging from social insects such as bees and ants, to plant vernalisation and variations between identical twins – I felt that the time is ripe to bring together scientists from many different areas. I also wanted this to be a symposium that would attract scientists from different areas to EMBL.

At EMBL, we want to understand the molecular basis of life. Until now, EMBL has been known for exploring genomic, molecular, structural and cell biology at the level of individual organisms. Looking ahead, we want to study organisms in the context of their physical and biological environments – not just in isolation. In order to truly understand life on Earth, we need to study organisms in nature, not just in the lab. One way to understand life at the molecular level will be to try to bring relevant ecosystems back to the lab, to measure and perturb them under controlled conditions. The speakers we’ve invited are experts from many different areas of biology or ecology, and will bring exciting new perspectives to our research.

The EMBO|EMBL Symposium: The Organism and its Environment will take place at EMBL Heidelberg, Germany, from 1-4 March 2020

What is the greatest benefit of this symposium for the scientific community?

The symposium is an opportunity to address how organisms are influenced by a changing environment. It will bring together different research disciplines and go beyond pure genetic or ecological perspectives of phenotypic variation. Geneticists, molecular biologists, evolutionary biologists and ecologists do not necessarily meet under ordinary circumstances. This meeting will enable such interactions and cross-fertilisation.

What will be the main highlight of the symposium?

Today we are in a unique position to address the complexity and dynamics of life at multiple scales, from molecules to ecosystems. We also need to consider the idea that change – including in the environment – is not necessarily a bad thing. After all, without change, evolution could not occur and none of the amazing biodiversity of life on our planet would exist! I hope that a highlight of this symposium will be some wonderful new insights into evolutionary processes.

References

Holley D., (2017). General Biology II, Organisms and Ecology. Indianapolis: Dog Ear Publishing, 898.

World Wildlife Fund, (2018). Living Planet Report: Aiming higher [PDF] https://wwf.panda.org/knowledge_hub/all_publications/living_planet_report_2018/ [Accessed 25 July 2019].

https://wwf.panda.org/knowledge_hub/all_publications/living_planet_report_2018/

However the WWF DG is quoted by several articles as describing the crisis as mind-blowing, for example: “https://www.voanews.com/science-health/report-earth-has-lost-60-percent-its-wildlife-1970

Organoids: Modelling Organ Development and Disease in 3D Culture

EMBO | EMBL Symposium – Heidelberg, 10-13 September 2018
Meeting report by Veronica Foletto

Following the huge success of the 2016 symposium ‘Organoids: Modelling Organ Development and Disease in 3D Culture’, Hans Clevers, Jürgen Knoblich, Melissa Little, and Esther Schnapp joined forces to organise a second such symposium this year. On the afternoon of 10 September, 460 scientists from all over the world gathered in the auditorium of the EMBL Advanced Training Centre (ATC) in Heidelberg.

Hans Clevers, a leading expert on organoids, welcomed everyone and led the opening session. The first keynote lecture was given by Jürgen Knoblich, who reported on progress in his lab using cerebral organoids to model the complexity of the human brain and, in particular, to study microcephaly. The subsequent talks showed how organoids derived from different tissues provide useful models for the recapitulation of certain diseases – such as Helicobacter pylori infection and secretion of the VacA toxin in the stomach, as discussed by Xuebiao Yao – or models of early development, with Nicolas Rivron introducing the blastoid: a type of organoid similar to an early embryo, which can be used to study developmental processes in 3D.

The second day began early with an interesting ‘Meet the Editors’ session, in which scientists had the chance to talk directly to editors working for many scientific publishers (Springer, Nature, The Company of Biologists, Wiley, Cell Press and EMBO press) and to understand their vision.

Afterwards, Meritxell Huch chaired the session ‘Stem Cells and Development’, in which scientists presented advancements in the use of cerebral (Wieland Huttner) and pancreatic (Anne Grapin-Botton) organoids for deciphering cellular mechanisms during human development, and of gastruloids for studying the patterning of the antero-posterior axis (Denis Duboule). Near the end of the session, Bon-Kyoung Koo described how to efficiently use CRISPR technology to perform genetic studies in intestinal organoids. The session ended with a series of 2-minute flash talks, after which networking and interactions were encouraged during lunch, where there was an opportunity to meet the day’s speakers.

The beautiful helices of the ATC then provided the venue for the first poster session, where around 90 presenters had the chance to discuss their research with fellow scientists, editors, and a scientific evaluating committee. It was absolutely inspiring to see how many people work on organoid research!

The afternoon session, ‘Organoids from tissue stem cells’, included talks on organoids derived from taste stem cells (Peihua Jiang), cochlear cells (Albert Edge), and intestinal cells (Hans Clevers). Madeline Lancaster explored the possibility of studying differentiated human cerebral organoids which self-assemble in the stereotypic organisation of the early human embryonic brain and have functional motor-neuronal circuits.

Among this ‘zoo of organoids’ – as humorously defined by Jürgen Knoblich – there was room for organoids derived from snake venom glands (Yorick Post): the organoid toolbox seems to be extendable to non-mammalian cultures as well!

On Wednesday morning, James Wells introduced the session ‘Recreating organs from pluripotent stem cells’. This addressed cell fate decisions in the developing mouse thyroid gland or lung (Sabine Costagliola), the human lung (Jason Spence and Hans-Willem Snoeck), the human salivary gland (Cecilia Rocchi), and the human forebrain (Flora Vaccarino), studied primarily through single-cell transcriptome and enhancer analyses. Finally, it was the turn of Mathew Garnett, who started by showing that the worldwide number of new cases of cancer each year is around twice the population of Switzerland.

Interested in using precision organoid models to study cancer and patients’ responses to treatment, Garnett is now contributing to the development of the Human Cancer Models Initiative. Its goal is to create a new generation of molecularly annotated cancer models, which will be widely beneficial to the scientific community.

After the second poster session, there were talks on ‘Organoids and disease modelling’, introduced by Anne Grapin-Botton. Among the topics covered were the use of 3D organoids to model liver regeneration and disease (Meritxell Huch), and to study cancers of the bladder (Michael Shen), pancreas (David Tuveson), breast (Martin Jechlinger), and colon (Henner Farin).

The day ended beautifully with the conference dinner in the EMBL canteen and the delightful live music that brought together the diverse group of researchers once again.

The final day of the conference was dedicated to ‘Cells and materials in regenerative medicine’. Matthias Lutolf discussed some of the ongoing efforts in his research group to develop next-generation organoids through tissue engineering. Meritxell Cutrona reported advances in nanoparticle tracking in 3D structures, which is particularly useful for drug delivery. Lakmali Atapattu described 3D bioprinting of tumoroids. Henrik Renner presented a high throughput-compatible workflow for the generation, culture, and optical analysis of neural human organoids. Rob Coppes and Melissa Little reported on promising progress in improving cancer treatment, using glandular and kidney organoids, respectively. James Wells gave a talk on the applications of gastrointestinal organoids, concluding with some food for thought for the audience: “It is better to collaborate, than to compete.”

The Symposium ended with the poster prizes, sponsored by EMBO Reports, EMBO Molecular Medicine, and Sartorius. Personally, I found these four days extremely stimulating, full of opportunities for interaction and discussion. I believe most of my fellow researchers got the same feeling: 3D organoid systems are revolutionising molecular biology and driving the development of better clinical therapies, and we are all contributing to this revolution.

What will we be able to achieve with organoids in two years’ time?

Stay tuned, the meeting will be back in 2020!

@LunardiLabCIBIO