The EMBO|EMBL Symposium ‘Cellular mechanisms driven by phase separation’ occurred from 9-12 May 2022. The meeting was held on-site and virtually, with a record of over 500 attendees from all over the world. Seven lucky candidates got fellowships from the EMBO and the EMBL Advanced Training Centre Corporate Partnership Programme. These candidates travelled across the globe from India, the Czech Republic, Saudi Arabia, Poland, and Spain to attend the conference. The four-day program featured seven sessions, 50 talks, discussion panels, and countless posters showcasing the newest scientific advances in the field.
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Join #EESPhaseSeparation to discuss & learn from scientists from different fields about condensates in biology and disease.
It was my first time attending and reporting during a virtual conference organized by EMBO & EMBL. The meeting was scheduled systematically, with links to presentations, posters, chats, and other information provided online on the login page. Moreover, the newly added discussion tab allowed the users to meet editors, talk about articles, and get advice on how to publish them. If you want to collaborate with someone or have a career-related question, this is the right place for you! You could also raise questions that come to your mind and have a fruitful discussion with other attendees.
LUMICKS organized a pre-conference workshop to Unravel the Biophysical Principles Underlying Biomolecular Assemblies Using Optical Tweezers.
The revelation that various intracellular vesicles can be generated without lipid membranes has opened up new areas for research in cell biology and related domains. Transcriptional clusters, stress granules, heterochromatin domains, and DNA repair compartments are all instances of membrane-less compartments. These biomolecular assemblages enable the enrichment or exclusion of specific biomolecules, the spatial organization of nucleic acids, and the acceleration of biological events.
The panelists provided many exciting ideas from decades of expertise in their field, which is typically not readily available, particularly to early-career scientists.
The conference kicked off with opening remarks given by the scientific organizers Simon Alberti, Dorothee Dormann, Edward Lemke, and Tanja Mittag. The schedule was jam-packed with great and diverse talks covering significant aspects and hot topics in phase separation. There were seven sessions, each focussing on a different element of phase separation, thereby beautifully orchestrating a story that can helped one sequentially understand the topics and stay hooked to the presentations.
The highlights from the conference were instantly reported on Twitter using #EESPhaseSeparation. If the data presented during a talk has already been published, there is usually a link to the tweet’s associated paper(s).
Stephen Michnick (Université de Montréal, Canada)
Spoke about Saccharomyces cerevisiae and how, around 1 billion years ago, the genome of the budding yeast Saccharomyces cerevisiae underwent a significant decompaction due to the loss of histone H3 lysine 9 methylation. He explained how this decompaction could have caused a more remarkable ability to evolve due to processes such as highly high meiotic levels, mutation, and recombination rates. As a result of the improved evolvability, unique characteristics have made it an ideal eukaryote model and a biotechnological model.
Dr. Michnick gave instances of how variations in the mechanical characteristics of chromatin reflect locally and globally genome adaptations, indicating phase separation induced by histone post-translational modifications and resulting changes in histone exchange rates.
Rosana Collepardo Guevara (University of Cambridge, UK)
The separation of chromatin and its associated proteins in the liquid-liquid phase separation is gaining traction as a method for explaining the organization of the Eukaryotic nucleus. In this talk, Dr. Collepardo Guevara elaborated on how we can resolve individual nucleosomes within sub-Mb chromatin domains and phase-separated systems using multiscale chromatin approaches that integrate atomistic representations of DNA and proteins. The models presented by her enable us to link molecular and biophysical characteristics of individual nucleosomes to chromatin phase separation regulation. She explained how the variables that keep nucleosomes organized in a disorderly, liquid-like fashion within single chromatin arrays also favour phase separation of a solution of chromatin arrays.
Sara Cuylen-Häring (EMBL Heidelberg, Germany)
The inherently disordered protein Ki-67 covers the surface of the mitotic chromosome, the most enormous membrane-less cellular structure. Previous research has shown that Ki-67 has two functions. Ki-67 acts as a surfactant in early mitosis, preventing chromosomes from collapsing into a single chromatin mass, yet it actively promotes chromosomal clustering towards the mitotic exit. It’s still a mystery how Ki-67 flips between these two opposing activities — chromosomal dispersal and chromosome clustering.
Dr. Cuylen-Häring showed that when all chromosomes combine into a single cluster during anaphase beginning, Ki-67’s biophysical properties alter dramatically. The amphiphilic nature of Ki-67 is lost as the molecular brush structure collapses and the protein’s soluble pool condenses. Her research reveals a cell-cycle-dependent mechanism that regulates the individualization and coalescence of cells.
David Zwicker (Max Planck Institute for Dynamics and Self-Organization, Germany)
He elaborated on how biological cells are made up of thousands of different macromolecules that organize themselves into condensates and other structures. How can numerous distinct condensates reliably develop despite massive composition changes? He presented a novel numerical approach for determining coexisting phases in multicomponent systems. This method helps to maximize component interactions, similar to how evolution may have optimized biomolecule interactions. Random or contrived interactions perform worse than evolved interactions in producing a defined number of phases. The improved interactions also resist perturbations and allow for quick adaptation to new phase counts. He detailed how genetically programmed biomolecule interactions can govern the production of condensates in various ways.
Mrityunjoy Kar (MPI-Cell Biology and Genetics, Germany)
The creation and breakdown of membrane-less biomolecular condensates such as RNA-protein granules are linked to phase separation of RNA binding proteins with disordered prion-like domains and RNA binding domains. DLS, nanoparticle tracking analysis, fluorescence anisotropy, microfluidic confocal spectroscopy, and TEM investigations of cluster size distributions in sub-saturated solutions of phase-separating RNA binding proteins from the FUS-EWSR1-TAF15 (FET) family were presented by him. He elaborated how in saturated solutions, these systems exhibit heterogeneous cluster distributions. While the most prevalent species are small clusters, cluster size distributions appear to be heavily tailed. Furthermore, when bulk concentrations rise, cluster size distributions continue to trend toward bigger values. DLS tests also reveal that these clusters are reversible when diluted and concentrated, and FRET measurements show that protein molecules interchange between clusters and the bulk solution. At and beyond the saturation concentration (csat) of phase separation, these clusters coarsen and produce condensates. These observations are readily explained in terms of associative polymer theories.
Martin Wühr (Princeton University, USA)
He briefed about membrane-bound organelles like mitochondria and membrane-less biomolecular condensates (BMCs) like the nucleolus achieve compartmentalization, which is a fundamental aspect of eukaryotic life. BMCs that have been identified have liquid-like characteristics and are often viewed on a 1 µm scale. He further explained that they’ve largely been investigated using microscopy to look at certain proteins. Several dozen BMCs have been identified so far, each with a different function, such as transcription regulation, RNA management, or signaling, and their dysfunction can result in illnesses. However, it is unknown how BMCs are used in the cellular organization or at what length scale they form. At the scale of 100 nm, he showed his data that at least 18% of the proteome is structured into mesoscale BMCs. They have used differential pressure filtration, size exclusion, and dilution procedures to explore the structure of native cytoplasm on a global scale utilizing quantitative proteomics. By examining protein penetration through porous substrates with known pore diameters, they were able to confirm mesoscale sizes using imaging below the diffraction limit. The results he presented revealed that at unexpectedly short length scales, eukaryotic cytoplasm organizes itself extensively via liquid-like assemblies.
Danfeng Cai (Johns Hopkins Bloomberg School of Public Health, USA)
In 22.5 percent of papillary renal cell carcinomas (PRCCs), the Hippo pathway is dysregulated, resulting in hyperactivated YAP1/TEAD1 activity. However, it is unclear how YAP/TEAD1 contributes to PRCC development. His research group found that transcription factor TEAD1 generates liquid-like nuclear condensates inside PRCC patient-derived cell lines using super-resolution imaging and PRCC patient-derived cell lines. TEAD1 condensates appear in a variety of sizes and functions, which is intriguing.
Smaller, sub-micron-scale TEAD1 condensates facilitate active transcription, whereas larger, micron-scale TEAD1 condensates repress transcription: they lack YAP1, are devoid of active transcription markers BRD4 and H3K27Ac, and are found in different heterochromatic nucleus compartments.
Keynote lecture: A fluid paradigm for biological organization, Clifford Brangwynne (Princeton University, United States of America)
Living cells are frequently misunderstood as machines on a factory floor, operating through a clockwork-like series of interactions among their biomolecular building pieces. However, internal cell activities are far more wet and active than many textbooks would have us assume. Research integrating concepts from materials physics and cell biology has ushered in a new paradigm for understanding how this chaotic intracellular environment is brought to order through the collective condensation of disordered proteins into droplets of living information throughout the last decade. Intracellular condensates are viscoelastic states of biomolecular matter that aid dozens of intracellular processes and appear to be at the root of malignancies and neurological disorders such as Alzheimer’s and ALS.
After an almost four-year-long break, the on-site event resumed at the EMBL campus in Heidelberg. People enjoyed networking and interacting with others which boosted their morale. The pandemic has taught us to come up with new approaches to our actions, and virtual meetings are one of them. Many people across the globe benefitted from the conference being set up in a hybrid format and enjoyed the amount of knowledge that this event showered upon them.
This blog post is written by Ritvik Gupta, Master’s thesis student at Didier Stainier’s Group, Max Planck Institute for Heart and Lung Research, Germany, pursuing BS-MS at IISER Mohali.
This year’s EMBO|EMBL Symposium: New Approaches and Concepts in Microbiology took place 7-9 July 2021. For the first time in its history, the meeting was held virtually, with a record of over 650 attendees from all over the world. The three day programme featured six sessions, 36 talks, discussion panels and countless posters showcasing the newest scientific advances in the field.
This was my second time reporting during a virtual conference organised by EMBL, the first one being the EMBO Workshop: Molecular Mechanisms in Evolution and Ecology. It is interesting to note, even though the two meetings started with quite different scopes and aims, over time they began to resemble one another. Both meetings welcomed topics in microbiology that use cutting-edge techniques to disentangle and unravel microorganisms’ intricate worlds. The two meetings followed a similar format, which included a fairly intuitive online platform with links to presentations, posters, chats and a variety of other information prepared by the organisers.
As part of New Approaches and Concepts in Microbiology, three special pre-symposium sessions explored transitioning to starting a lab, the nooks and crannies of publishing presented from the editor’s perspective and the future of scientific meetings in a post-pandemic world. The panelists shared many insightful ideas distilled from decades of experience in their work, and usually this type of knowledge is not so readily available, especially to early-career scientists.
From my personal perspective, the pre-symposium session on the future of scientific meetings was one of the most interesting, and is also a topic that will affect everyone in the scientific community. Gerlind Wallon representing EMBO shared results of a recent survey in which scientists were asked what they expected from meetings in the future and how did they perceive the online meetings that became a sudden reality for the scientific community, since the onset of the pandemic.
The scientific programme of the conference was fully packed with impressive and wide-ranging talks tackling most of the ‘big’ areas and pressing topics in microbiology. The first day was dedicated to systems biology, followed by the environment and antibiotics. The presentations on the second day dealt with regulation, signalling, protein machines and cell biology. The final day’s sessions covered novel approaches to study pathogenesis, infection, and microbiomes.
A common and reoccurring theme in many talks was the role of viruses in microbial systems and processes. The importance of that topic was strongly emphasised during the 1st day’s panel discussion on phage-microbe interactions, which highlighted some new and exciting perspectives on viruses.
The highlights from the conference have been instantly reported on Twitter using #EESMicrobiology. If the data presented during a talk has already been published, there is usually a link to the associated paper(s) in the tweet.
Onsite to virtual to hybrid?
Pandemics brought many tragic events, but on the other hand, it gave us a chance to rethink many issues and come up with alternatives for our actions. Virtual meetings are perhaps one of the broadly acquired tools, which in my opinion should further be used to make science more available for people and lower our impact on the environment. Will the next “New Approaches and Concepts in Microbiology” be held in a hybrid format?
Event Report by Apoorva Baluapuri, University of Würzburg, Germany
RNA and DNA were first described by the Swiss biologist Friedrich Miescher in 1868. About 150 years later, we stand at crossroads of the two disciplines which have arisen as a result of dedicated research on both molecules. The first EMBL symposium on the connections between transcription and DNA replication/repair research was a major step forward in combining the progress from wide ranging topics, thus generating a consensus on how gene expression and DNA transactions cooperate.
The symposium, which was the second one from EMBL this year, was scheduled just a day after International Women’s Day, and that aligned very well with the equally represented line-up of speakers and organisers!
The titular opening session was dedicated to transcription-associated genomic instability where all aspects of R-loops and ribonucleotide excision repair in transcription coupled DNA double strand break repair were covered. For example, Gaëlle Legube(CNRS – University of Toulouse, France) expanded in great detail on the influence of DSB-induced chromatin conformation and the strong potential of 3C-based technologies, while Elodie Hatchi (Dana Farber Cancer Institute, Boston, USA) explained about her recent publication in Nature concerning the impact of BRCA1, RAD52 and PALB2 on small RNA-driven DNA repair.
Eventually, we switched over to a more translational theme with Rushad Pavri (IMP, Vienna, Austria) who spoke about the relation between DNA replication timing and frequency of oncogenic translocations.
This time around, the poster presentation sessions were equally dynamic with topics being covered from role of RBMX in RNA processing (Sara Luzzi, University of Newcastle) to role of MYCN in reconciling elevated transcription levels with DNA replication (Dimitrios Papadopoulos, University of Würzburg, Germany).
To end the first day, Philippe Pasero (CNRS, France) tried to answer the old question of the chicken or the egg in terms of toxic R-loops, if they are the cause or consequences of DNA replication stress, while Andrew Deans (St. Vincent’s Institute of Medical Research, Australia) explained about fork re-modellers as a general mechanism of R-loop removal.
The second day started out on a high note by a talk on the consequences of DNA damage and heat shock on Pol II from Jesper Svejstrup. Prof Svejstrup recently moved his lab from the Francis Crick Institute in London to the University of Copenhagen (Faculty of Health and Medical Sciences).
To make things even more exciting at the symposium, Martin Eilers (University of Würzburg, Germany) spoke about conflict resolution by MYCN between “friends and foes”, i.e. Pol II and replication fork. This was followed by talk by Marco Foiani (University of Milan, Italy) who showed the role of ATR in nuclear integrity.
In between the breaks, the participants eagerly shared their setup of how they were joining the virtual conference:
Along with this fun, the second day’s poster session continued with equally interesting topics as the previous day. The virtual conference platform provided by Engagez came across as a handy tool in coming as close as possible to the in-person poster presentations.
Frédéric Chédin (University of California, Davis, USA) closed the day by talking about interplay between splicing and R-loops.
In the next two days, a wide variety of topics and methods were covered. For example, Nick Proudfoot (University of Oxford, UK) dazzled with correlation between R-loops and antisense transcription while Petra Beli (IMB, Mainz, Germany) moved the focus from genomics to proteomics with èlan. She spoke about a method called “RDProx” which maps R-loop proximal proteome in a native chromatin environment.
Also, junior group leaders like Marco Saponaro (University of Birmingham, UK) answered what happens to replication when it encounters transcription and Madzia Crossley (Stanford University, USA) showed CytoDRIP-blots to probe RNA-DNA hybrids on gels which showed that SETX and BRCA1 loss, along with splicing inhibition, results accumulation of RNA-DNA hybrids in cytoplasm!
All along the talks, whichever questions (which, by the way, were in majority from younger researchers) didn’t get answered, were posted and responded to in the “Forum” section: this actually became a valuable summary of quite a few topics.
The networking options were also in abundance, be it the Virtual Bar mixer, or Meet the Editors session on the online platform. Given that editors from elite journals like EMBO, PLoS Biology etc. were present, it gave a nice opportunity for the researchers to gauge where their next big story could find a good home.
In summary, the symposium gave the feeling of being cozy without being too small and specific in terms of the topics covered, and benefited both the experienced and young researchers in an equal way. It was a common understanding and expectation among the participants that this symposium would perhaps be held in person next time if possible.
Event report by Jesus Victorino, PhD student at the Universidad Autonoma de Madrid, Spain.
Four Novembers ago, I arrived in Heidelberg on my 24th birthday which I celebrated carrying my first poster as a freshmen PhD student. Back in those days, a hypothesis with an outline of my future experiments was all I captured on that A0 laminated fabric poster. Four years and a PhD later, there could not be a better place to show my results right before defending my thesis than at the very same EMBL conference: From Functional Genomics to Systems Biology. Well, not exactly the same. This time we could not enter the ATC building and walk through its double-helix bridges, since the event took place virtually.
The organising committee managed to set up an online conference, enabling more than 270 participants to share their thoughts and results about genomics, proteomics and imaging. And we got to see everybody’s living room! Although the schedule differed from usual conferences in Europe (13:00-20:00 CET), it broadened the audience by allowing people from other countries to attend. And all that without taking a plane or paying for a hotel room, which significantly decreased the required budget to attend the conference and the carbon footprint we left behind.
I found several additional aspects of attending a virtual conference very exciting. On the one hand, the lack of big crowds in a large room with a single microphone and a line of researchers waiting for their turn, encouraged me to ask questions to the speakers. I simply felt more comfortable. Zoom allowed a record of the many questions asked, and those that were not answered due to time constraints were posted on a Slack channel created to coordinate the meeting. The Slack channel was incredibly helpful not only to increase the feedback with more scientific questions & answers but also to improve networking, especially for the poster session. I hope we keep using a similar virtual space that enables participants to contact other scientists even for onsite conferences.
At least in my experience, the poster session worked out way better than expected, which was a pleasant surprise. I found myself talking with researchers (mainly PhD students) for most of the session, which I never experienced before. I took advantage of the Slack channel to advertise my poster and also to interact with the presenters of other posters I was very interested in. Magically, people were showing up in my Zoom room and I found that breaking the ice virtually was easier than in a real room, since there was no awkward moment in which you hesitate to interact with the presenter, or the presenter does not know whether you might want to know more about his/her research or are just passing by.
On the other hand, I found the platform where we should upload the posters very inconvenient. Instead of uploading our posters in PDF and being able to chat through Slack, Zoom or similar, we had to use ‘iPosterSessions’ and re-shape our posters to fit the virtual and very rigid format of the website. I found the platform non-intuitive and there were incompatibilities, at least with my computer, for the ‘chat’ and ‘contact author’ options within it. Besides, we had to provide a way to virtually meet other participants and present our posters on our own (e.g. a Zoom room or similar), which was not very straight-forward,, and not everyone might have had access to it. Having said that, this was basically the only issue I experienced during the entire meeting – the lectures worked perfectly, we discussed exciting projects and the poster sessions were very fruitful.
Another great choice from the organisers was to schedule ‘meet the speakers’ sessions. I enjoyed meeting three of the speakers together with other early career researchers where we could exchange thoughts and impressions. I think this is very important to train students on how to interact with more senior researchers and I have rarely found a dedicated spot for this at international conferences.
During the conference, all lectures and short talks were divided into four main thematic areas: quantitative genomics, quantitative proteomics, quantitative imaging and single-cell genomics. Here’s my pick from the panel of speakers that I feel represents the essence of each area.
Transcriptional enhancers were the main characters of the quantitative genomics sessions, where different labs addressed the question of how the control of gene regulation affected phenotype in a different way. The fruit fly embryo was one of the preferred model organisms and was used by the team led by Thomas Gregor to study how the spatial organisation of the chromatin affects transcription at the eve locus. Justin Crocker also showed beautiful Drosophila embryos that they used as a test tube to understand the logic of a developmental enhancer and the phenotypic impact of its mutations. With respect to this study of the genotype-to-phenotype impact but in the context of human genome variation, Bart Deplancke told us about how non-coding variants affect gene expression in immune cells unveiling implications in leukemia.
Following with genomics, we witnessed the power of sequencing technology but at the single-cell level to understand physiology and disease. In this thematic area, we learnt with Antonio Lentini about gene expression and silencing at the X chromosome and Dana Pe’er talked about its uses to study development and cancer. The work presented by Henrik Kaessmann was very impressive and stood out not only for the use of thousands and thousands of cells, but for studying spermatogenesis in twelve different mammals providing a valuable resource to study this process across evolution.
The quantitative proteomics sessions taught us about the promising years that we face since improved technology might quickly move the field forward. Bernhard Küster showed how proteomics and in vitro models can be used to investigate drug response to cancer treatments. Although the massive characterisation of the proteome is yet not comparable with the performance of sequencing technologies in the genomic field, Michiel Vermeulen’s talk illustrated how to combine genomics and proteomics to understand cancer biology and identify new important players and therapeutic targets.
The fourth thematic area was quantitative imaging in which Emma Lundberg talked about high-throughput imaging and its use to dissect the human proteome. We could appreciate the potential of the analysis of massive amounts of imaging data in the work presented by Professor Lundberg where they involved hundreds of new proteins in cell cycle and identified new putative roles for proteins they found to localise in multiple subcellular compartments. Super-resolution microscopy could not be missing at this conference and Suliana Manley nicely showed how to use it to study mitochondrial organisation and dynamics.
Outstanding science and fresh data in a very interactive environment summarises the experience at the conference, where I was glad to see that many of the projects presented were shared in the form of preprints. I collected them and included in this list of preprints at the #EMBLOmics for attendees who might want to know more about some of the talks and for those who did not attend and might want to have a flavor of this conference.
Of course, it would not have been a proper EMBL meeting without the final gathering and concert. The event ended with a fantastic concert by Lazy Fur which really put the icing on the cake –the concert is recorded here, so you can listen to their nice voices while you prepare for your next experiment. I really thank the organisers for all the effort to make the screen disappear and feel like in a non-virtual event.
Since 2020 has shaken the way we interact with people, scientists, like everyone else, have had to quickly adapt to the new circumstances. In the academic world, conferences play an important role for scientists to share their recent advances and build their contact network. While it was already under debate how to reduce the ecological impact of such a tremendous flow of researchers travelling all over the world, virtual conferences did not seem to launch. All of a sudden, the global pandemic situation has rapidly turned this will to a necessity, leaving us no other option but to evolve. The good thing is that virtual conferences seem to be reasonably meeting our expectations, providing with a more sustainable way of sharing our data and interacting with each other. They offer both advantages and disadvantages with respect to in-person events but undoubtedly have accelerated our steps towards including more virtual conferences in the calendar once we go back to a ‘normal situation’.
About the author
I’m Jesus Victorino, PhD student working in gene regulation and member of the preLights community, a platform to disseminate science and the role of preprints in Biology.
From our virtual event reporter Magdalena Wutkowska, The University Centre in Svalbard / UiT – The Arctic University of Tromsø, @m_wutkowska
The EMBL conference on Molecular Mechanisms in Evolution and Ecology took place from 30 September to 2 October 2020. The meeting – which had its first iteration in 2008 as a workshop on Evolutionary and Environmental Genomics – has gained a broader context over time not limited to evolution and yeast, which was reflected in this year’s program.
This year for the first time the conference was held virtually. Six sessions over three days encompassed vast topics such as Evolutionary Systems Biology, Systems and Synthetic Biology, Assembly and Evolution of Microbial Communities and Experimental Evolution and Evolution of Complex Traits. Between the sessions, participants could join ‘meet the speaker’ coffee breaks, poster sessions and short talks. Below are just some of the highlights from the main sessions.
SESSION 1 – Evolutionary Systems Biology
The first session on Evolutionary Systems Biology was chaired by Gianni Liti (University of Nice, France), who first outlined the history of the meetings since 2008.
Matthew Goddard (University of Lincoln, UK) spoke about the nature of interactions between yeasts and other organisms through traits. Saccharomyces cerevisiae, just as any other organisms, evolved in the presence of other species. The existence of a trait does not have to be adaptive, and evidence of increased fitness is required to make such a statement. Goddard presented a case study of interactions between yeasts and fruit flies. Yeast produce ferments and volatiles that attract fruit flies, whereas yeast could benefit from dispersal capabilities provided by fruit flies. Some experimental evidence support the notion that the yeast – fruit fly association is mutualistic. However, recent studies showed no supporting evidence, i.e. no clear individual volatile correlated with general attraction of fruit flies. Moreover, the dispersal advantage for yeast is most likely a stochastic by-product of this interaction. Thus, the interaction is not driven by adaptation, but more likely by exaptation, which is a shift in the trait function during evolution. This talk urged us to examine the evidence for increased fitness closely, while looking for adaptive traits.
Anastasia Stolyarova (Skolkovo Institute of Science and Technology, Russia) posed the question whether epistasis shape variation within populations. Many natural populations are characterised by relatively low genetic variability; therefore, it is not possible to see strong epistatic selection between polymorphisms. Thus, to study non-random associations of alleles (linkage disequilibrium), she used the world’s most variable eukaryotic species Schizophyllum commune, which differs by up to 20% of nucleotide diversity at neutral sites. Based on 54 genomes from two distinct populations, she found that in both populations between nonsynonymous mutations were higher than between synonymous ones. Additionally, within-gene linkage disequilibrium between nonsynonymous mutations was higher when compared to that between the genes. Model simulations suggested that this phenomenon resulted from abundant epistasis.
Toni Gabaldón (Barcelona Supercomputing Centre, Spain) talked about ‘origin and evolution of hybrid yeast pathogens’. Novel hybrid lineages may display innovative traits that could facilitate successful colonisation and growth in new settings, including human hosts. Emergence of pathogenesis in hybrids was studied by genomic comparisons of closely related pathogenic and non-pathogenic species within Candida clade that differ in virulence. Hybrids turned out to be not only common among some clades, but they can also survive for a long time.
Aaron M. New (Centre for Genomic Regulation, Spain) spoke about deciphering how genetic variants quantitatively change protein characteristics in a long evolutionary perspective. Predicting the outcome of mutation combinations is high in additive models, but drops in sign epistasis, which is crucial for evolution. This problem was explored in a model paralog pair of yeast genes involved in galactose metabolism and signalling: GAL1 and GAL3, that differ in their biochemical properties. The study identified a mutation in GAL3 that was responsible for sign epistasis by modifying existing destabilising effect to a stabilising one on protein folding. These mutational changes in sensing/signalling proteins are of evolutionary importance for the emergence of new phenotypes.
In his talk, Antonis Rokas (Vanderbilt University, USA) focused on ‘the evolution of the buddying yeast biodiversity’. His lab members and collaborators used buddying yeast (Saccharomycotina subphylum) to decipher genetic bases for metabolic diversity at an unprecedented scale. This research revised current understanding of drivers of evolution in eukaryotes, both in genomic and phenotypic aspects. As it turned out, the gene conservation was shown to be not universal. Losses of genes or traits were pointed out as important evolutionary forces, whereas horizontal gene transfer, although identified only a few times, had an essential effect on evolutionary trajectories.
Pedro Beltrao (EMBL-EBI Hixton, UK) shared novel insights on ‘evolution and functional relevance of protein phosphorylation’. Phosphorylation uses enzymes to catalyse reversible attachment of phosphoryl groups that (de)activate many types of molecules, including proteins. Phospho-regulation is of fundamental importance for post-translational protein modifications, that impacts the decision process in the cells and can be an underlying mechanism in many diseases. His research on ~500 phosphorylation-deficient mutants across 100 stress conditions explained that roughly half of them had no phenotypes and the contribution to fitness is not equal between phosphosites. Relevance of these sites for phenotypes can’t be predicted by using only one variable or feature. Advancements in understanding evolution of function of protein phosphorylation requires more insights from cell biology and mechanistic understanding.
SESSION 2 – SYSTEMS AND SYNTHETIC BIOLOGY
Kiran Patil (EMBL Heidelberg, Germany) held the second session on Systems and Synthetic Biology.
Claudia Bank (Gulbenkian Science Institute, Portugal, and University of Bern, Switzerland) discussed considerations and challenges in the process of using empirical data in fitness landscapes models in predicting evolutionary outcomes. The fitness landscape theoretical framework was proven to be a platform for testing evolutionary hypotheses. Large discrepancies in experimental data have been identified in fitness arose from single-mutations and epistasis across environments. However, it is still not clear how to reliably predict mutation effects across different environments using these models.
Jens Frickel (VIB–KU Leuven, Belgium) explained issues and uncertainties connected to mechanisms buffering mutations and its role in organisms fitness. Some gene products blur the effect of many mutations; therefore, they can act as buffer against genetic variation. The most studied buffering gene is HSP90 that assists accurate folding of mutated proteins. Genome-wide screens of yeast genes in 5000 strains allowed for identification of the gene ontology categories of genes involved in buffering activities that increase the average relative fitness. The most potent categories include chromatin binding, chromatin remodelling and unfolded protein binding. He presented directions of current and future research aiming to understand buffering mutations.
In his talk, Angad Mehta(University of Illinois at Urbana-Champaign, USA) focused to experimental explorations of mitochondria and chloroplast evolution. The endosymbiotic theory has been backed by molecular evidence from sequencing studies. However, the process of entering the cell by endosymbionts and coevolution with the host are not understood. He used synthetic biology tools to test experimentally investigate and evaluate evolutionary scenarios of bacterial endosymbiont evolution and transformation into organelles. Engineered S. cerevisiae (lacking mitochondrial DNA) and E. coli (thiamin auxotroph) were used as host (providing required metabolites) and endosymbionts (providing the ATP). Further research focused on the evolution of yeast – E.coli chimaeras and number of mitochondria maintained within the complex. At the moment he is involved in similar studies modelling the evolution of cells with chloroplasts using S. cerevisiae and cyanobacteria.
Kyle Fowler (University of California, San Francisco, USA) spoke on how regulons can change across evolutionary time. Transcription networks are a source of evolutionary novelty and contribute to plasticity; therefore, research in this field is crucial to understand evolutionary processes. In this talk, Fowler presented some of the results from studies on gain of function in interactions between two transcriptional regulators MATα2 and MXM1. Results showed that functional, cooperative interactions could most likely evolve with ease and explain diversity in structures in regulatory networks. Common intra-molecular epistasis expanded the permissive sequence space allowing for 9% of all sequences to be functional.
Chang Liu (University of California, Irvine, USA) presented ‘synthetic genetic systems for continuous protein evolution in vivo’. Liu Lab and collaborators developed an error-prone orthogonal DNA replication system called OrthoRep. In this system, preselected genes can be mutated at rates 100,000-fold above the genomic mutation rates. In practice it can be employed to carry continuous in vivo evolution of the preselected genes with no off-target genomic mutagenesis. OrtoRep provides countless applications to evolve useful biomolecules (enzymes, biosensors, antibodies and many more), study adaptation (governing rules, uncovering pathways of adaptation) and perhaps predict evolution in natural systems.
SESSION 3 – ASSEMBLY AND EVOLUTION OF MICROBIAL COMMUNITIES
Sara Mitri (University of Lausanne, Switzerland) chaired the first session of the day on Assembly and Evolution of Microbial Communities.
She continued with a lecture, in which she explored co-evolutionary dynamics within small bacterial communities inhabiting highly stressful environments (metal-working fluids). In particular, Mitri elaborated on interactions and stability of these communities as well as the evolution of established interactions. High toxicity promoted positive interactions between species. These interactions, however, were not constant and could be moderated by the addition of amino acids, and interactions of toxicity with food availability. Series of experiments revealed that evolving alone led to competition and genome preservation, whereas co-evolution with other species led to neutral interaction and genetic loss. Species interaction highly depend on the environmental conditions. As species adapt to each other’s presence, these interactions may weaken over time.
Daniel Machado (EMBL Heidelberg, Germany) talked about two distinct strategies developing in co-occurring microbial communities explored by genome-scale metabolic modelling. Microbial communities showed striking polarisation at the trade-off landscape between cooperation and competition. With increasing size of microbial communities, members displaying one of these strategies differed in multiple aspects such as number of metabolic genes, nutrient requirements, metabolic dissimilarity, abundance and phylogenetic distance. Moreover, competitive and cooperative communities were shown to have distinct habitat preferences. Communities displaying either of these strategies respond differently to both abiotic and biotic perturbations in their environment.
Isabel Gordo (Gulbenkian Institute, Portugal) explained some aspects of gut bacterial communities evolution in mice models. She focused on two main topics: evolution of a single dominant strain of E. coli and evolution of an invader strain in the coexistence with resident E.coli. Studies on the first case revealed that both balancing selection and clonal interference were wide-spread within the guts. Coexistence of populations of bacteria with increased mutation rate and population without them can last for a long time. The effect of deleterious mutations in vitro was higher than from in vivo experiments, that lead to a conclusion that probably the deleterious effect of mutations was reduced by biotic interactions and is even lower in species-rich setting. Experiments on the second scenario showed that in the initial stages of the evolution of an invader was dominated by phage-mediated horizontal gene transfer. At later stage, mutations started to accumulate. In the last part of her talk Gordo emphasised the need of long-term evolutionary studies of these scenarios and presented selected unpublished results from her lab.
Jona Kayser (Max Planck Institute for the Science of Light, Germany) described mechanisms in which mechanical forces can affect evolution in dense cellular populations. These populations are found in yeast colonies, but also biofilms, embryos or tumours. Collective motion of cells in the dense colony moves other cells with them. Slow-growing mutant populations with drug resistance can be carried to the rim of the colony by fast-growing yeast that are sensitive to drugs. In case of a treatment during infection application of the drug could stop the growth of neighbouring wild populations and caused resurgent growth of the mutants that were drug-resistant and not outcompeted by fast-growing wild types. These mechanisms may lead to increased understanding of treatment design in antibiotic resistance infections and tumours.
Wenying Shou (Fred Hutchinson Cancer Research Center, USA) talked about disentangling molecular mechanisms causing rapid evolution of new metabolic interactions in cells undergoing nutrient-growth dysregulation. Through conserved mechanisms in eukaryotic cells, nutrients control eukaryotic cell states promoting or ceasing growth. During unnatural auxotrophic limitation(s) this regulation might fail, resulting in nutrient-growth dysregulation. In this state cell growth is not arrested despite of limitation in resources. Shou presented experimental evidence that cells in this state release unusual metabolites. As a consequence, these released metabolites may provide an unforeseen way of rapid evolution of new metabolic interactions with other organisms.
Tami Lieberman (Massachusetts Institute of Technology, USA) spoke on adaptive evolution of skin commensal bacteria. In Liberman’s research tracking evolution, instead of sampling over a long period, many colonies were sampled from different pores in a single time point. Some bacterial species can adapt by de novo mutations in healthy people while in other bacteria inhabiting human face there were no signals of adaptive evolution. Mutational rate was much lower compared to rapid spreading on the face skin. Pores can be seen as separate islands, where location within the pore can predict success more than fitness does. Populations within pores most likely are descendants from a single ancestor. Some of the strains expanded and diversified rapidly on individual humans. People are colonised by multiple lineages, probably coming from multiple independent colonisation events.
In her talk, Rachel Dutton (University of California, San Diego, USA) focused on the ecological interactions in cheese-rind communities. Dutton’s Lab uses cheese rind biofilms to deconstruction and reconstruction of the system in order to understand microbial communities. They found many species-specific effects within these communities; however, some effects were found conserved across species. Over the years, the lab brought evidence for fungi being essential players impacting bacterial biology by releasing enzymes, siderophores, volatiles, antimicrobials and by increasing bacterial mobility.
The next session was a roundtable discussion on Assembly and Evolution of Microbial Communities moderated by Jun-Yi Leu (Institute of Molecular Biology, Taiwan). The participants Maitreya Dunham (University of Washington, USA), Isabel Gordo (Gulbenkian Institute, Portugal), Gianni Liti (University of Nice, France) and Nassos Typas (EMBL Heidelberg, Germany) discussed the past, present and future of the field. They emphasised that although there have been many substantial advancements in high-throughput sequencing, there are some issues that are still lacking full understanding, for instance, mutations, gene copy numbers and its consequences for the fitness of organisms. Experiments on laboratory strains of organisms explore only a small proportion of mechanisms and genetic diversity. Thus, future research should focus beyond that. The complexity of microbial systems is high, they are impacted by many factors, and they themselves impact their surroundings and other organisms. Therefore, there is a profound need for collaboration between different scientific disciplines to produce novel cross-disciplinary approaches, efficient data integration methods and solutions to long-lasting problems. Some of the significant challenges in the field include developing efficient training programmes that would enable students to receive well-rounded education encompassing a variety of disciplines. Finally, current knowledge should be more efficiently transformed into real-life solutions and applications that could potentially tackle some of the critical global issues.
The third day of the conference started with a career development session. Guests Claudia Bank (Gulbenkian Science Institute, Portugal, and University of Bern, Switzerland) and Daniel Machado (EMBL Heidelberg, Germany) discussed critical issues in carrier development and its maintenance. Career paths can be very different and can involve switching between disciplines, between academic and non-academic sectors. Much of the discussion was focused on the application process, its stochasticity and not being discouraged by rejections. They highlighted the importance of mindful and self-compassion approach towards work, especially in academia. Keeping a work-life balance might be often overlooked, although it is an important issue that can affect well-being and also motivation.
SESSION 5 – EXPERIMENTAL EVOLUTION
Chaired by Jun-Yi Leu (Institute of Molecular Biology, Taiwan), the session opened with a presentation on yeasts’ synthetic genomic applications by Lars Steinmetz (EMBL Heidelberg, Germany). The talk started with a summary of discoveries and advancements in genome editing. Manipulating regulation of transcription factors were used to increase understanding of adaptation to heat in yeast. Extensive work on engineered yeast cells able to on-demand reorganisation of their genomes helped to study selection changes in transcript isoforms that can occur after these reorganisations. However, many questions in genome editing and design regarding the location of genes and design principles still remain open.
Sarela Garcia-Santamarina (EMBL Heidelberg, Germany) shared her research on current understanding the interplay of drugs and gut microbiome in vitro. Experimental evidence showed high prevalence of drugs affecting growth of bacterial strains, whereas bacteria can significantly alter concentration of many drugs. It is not clear if these effects observed in monocultures are consistent in communities. Comparing responses of monocultures and communities in response to different drugs showed emerging community behaviours, such as sensitisation of drug-tolerant strains and protection of drug-sensitive strains. These emergent behaviours were concentration-dependent and disappeared when concentrations increased. High levels of these stressors disrupt community protective traits. The protective properties can be partly explained by drug metabolisation.
Sinéad Collins (University of Edinburgh, UK) spoke on the use of experimental evolution to understand microbial response to climate change. Oceans’ phytoplankton is composed of diverse organisms that act as “tiny adaptor plugs” between organic and inorganic worlds. These two worlds undergo shifts due to climate changes, and by using one methodology, it is impossible to predict how would they react in short and long-time perspective. She employed microcosm experiments that provide direct links between cause and effect in manipulation studies mimicking climate change, i.e. temperature and CO2 concentrations. Using these tools, the studies explored epigenetic transmission in adaptation to changing and fluctuating environmental conditions.
Christopher Large (University of Washington, USA) spoke on genomic stability and adaptation of beer brewing yeasts during serial repitching in the brewery. Repitching (using yeast many times over multiple fermentations) serves as a method to perpetually maintain yeast populations in breweries, and it is a suitable procedure to study adaptation to the brewery environment by looking at copy number variation, mitotic recombination single nucleotide polymorphisms and insertions/deletions of bases in the genome. In these conditions brewing yeast continuously underwent domestication at a fairly rapid rate. Many related strains in different breweries adapting over time displayed the same structural variations that included mitotic recombination of specific chromosomes and aneuploidy.
Gilles Fischer (Sorbonne University – French National Centre for Scientific Research, France), talked about transient hypermutator subpopulations in yeast colonies. A continuum model of genomic evolution of cancer predicts three main ways in which aberrations (including mutations) accumulate a gradual, punctuated and catastrophic modes. Often, we think about genome evolution as a gradual accumulation of mutation. Yeast populations contain hypermutator subpopulations that originate from transient phenotypic mutator cells. These subpopulations increased in size under stressful conditions such as oxidative stress and could lead to systemic genome instabilities illustrating the possibility of the catastrophic mode of genomic evolution.
Virginia Cornish (Columbia University, USA) spoke on ‘expanding the synthetic capabilities of yeast’. Cornish Lab uses engineered yeast capable of carrying out in vivo mutagenesis and selection steps of directed evolution. These yeasts have been engineered to perform new functions that made them useful in many applications. For instance, they were used as synthetic biosensors to create cheap colorimetric essays that can be used for detecting pathogens. This and further work in this area can lead to many therapeutic applications in the future.
SESSION 6 – EVOLUTION OF COMPLEX TRAITS
Maitreya Dunham chaired the last session of the conference, which focused on the evolution of complex traits.
Joseph Schacherer (University of Strasbourg, France) talked about S. cerevisiae-wide survey of the evolution of complex traits. Existing knowledge on architecture, inheritance and phenotypic expressivity of complex traits is still poorly understood. Genomes and phenotypic resources generated for over a 1000 isolates of S. cerevisiae served as a platform to select strains for pairwise crossing and examination of complex traits in resulting hybrids. These hybrids were grown under 50 growth conditions in order to obtain phenotypic distribution of the offspring. Most of the cross/condition combinations were shown to have complex inheritance. The complexity across traits was found highly variable. The expressivity of complex traits was both variable and dynamic across strains in different conditions.
Melania Jennifer D’Angiolo (Institute for Research on Cancer and Aging, IRCAN, France) talked on the origin of genomic introgressions from a yeast living ancestor. Introgressive hybridisation is an important mechanism in evolution of species across kingdoms. They were frequently identified in many yeast populations; however, it remains unclear how they appeared in reproductively isolated species. In her research, D’Angiolo found a coexistence of hybrid ancestor and its descendants inhabiting the same ecological niche. It was proposed that the underlying mechanism involved genomic instability that made possible for the hybrids to overcome sterility.
Irene Stefanini (University of Turin, Italy) spoke about research on buddying yeasts’ associations with insects. S. cerevisiae are important components of grape berries microbiota; however, their numbers depend on presence of the grapes and fluctuate according to the seasons. They are rarely found on unripe grapes, but their number rapidly increases towards the end of the season. For a long time, it was not clear where do these organisms overwinter and how do they get back on grape berries. Yet, a complete local variability of yeasts was found in insects’ guts where they could overwinter and be transported back on the grape berries when they formed in a new season. Rarely observed yeast mating in nature was promoted in insect guts, including wasps. Recent genome-wide association of S. cerevisiae from wasp guts started to shed light on mutations important ecologically relevant fungal phenotypes.
Lucy Xie (Stanford University, USA) spoke on a newly described drug resistance mutation-independent mechanism found in Candida albicans. In contrary to mutation-dependent, the new high-frequency drug resistance called pararesistance involves epigenetic modifications. Common antifungal (fluconazole) in low doses induced pararesistance in up to 10% of cells. These numbers increased after addition of other substances. The induced pararesistance was still observed after more than 100 generations cultured in the absence of the drug. Understanding the intricacies of this mechanism could decrease medical treatment failures in fungal infections.
Tatiana Giraud (Evolution et Systématique Laboratoire ESE, Université Paris- Sud XI, France) spoke on “multiple convergent events of mating-type loci linkage through different rearrangements”. Giraud focused on smut fungi beneficial gene linkages called supergenes that provide adaptation advantages. Presented studies on prevalence, formation and evolution of supergenes increased understanding of this little-explored field.
Adam M. Feist (Denmark Technical University) spoke on an ongoing cross-disciplinary automated project for understanding adaptive laboratory evolution. The project consists of two main components hardware for high throughput culturing and complex experimentation procedures to obtain information on mutations and conditions in which they arise and with a customised software for processing the output data. Acquired experimental data are subsequently organised, described, analysed and become part of a database (ALEdb). A multi-scale annotation framework aims to identify critical mutations at different conditions and scales (from binding sites to large aggregated features such as COGs). Feist also explained the current focus on using the data for design and engineering purposes, as well as expanding the breadth and scope in the database. ALEdb is available as a web-based platform https://aledb.org/
After the last session, Kiran Patil held a speech with closing remarks and future outlook. Attendees were given access to all the conference materials, including posters and pre-recorded talks for two weeks after the conference had ended.