Author: Rianne

Marketing expert by day, cheese lover by night.

Return to onsite: our first in-person meeting in 2 years

A little over 100 participants from over 20 countries attended the first on-site meeting since the COVID-19 pandemic hit Europe in March 2020. And since then, we have been preparing for this moment. We just didn’t have a clue when it would come. And the rules of the ‘game’ kept changing.

Railli Pall

Raili Pall was the conference officer for the EMBO | EMBL Symposium ‘Biological oscillators’. She was in charge of the logistical side of the meeting.

“There were many last-minute changes and cancellations due to the ongoing pandemic and travel restrictions, and we had to adjust rapidly to the changes in the programme. In addition, there was an extra layer of complexity as we had to accommodate a mix of safety protocols and added regulations.”

But then the moment was there. Nervously, we were waiting for the first bus to arrive. Checking the screens, the rooms, the badges. We have done this countless times. But this time was different, after two years of only virtual events, we were back onsite.

Having started her position in 2020, at the beginning of the COVID-19 pandemic, this was also Raili’s first on-site meeting

“I was very excited, but definitely a bit nervous before the event began. As it was the first on-site conference for many participants after more than 2 years, I wanted everything to run smoothly.”

And it did! The atmosphere was great and everyone was in high spirits. The overall feedback from all the participants and speakers was extremely positive as well. Everybody was happy to be finally back to in-person meetings. The symposium helped delegates to discuss and develop new ideas together. There was plenty of interaction and space for interesting and inspiring discussions. In addition, the programme consisted of outstanding talks by leading experts, covering a broad range of topics. The on-site poster session was highly appreciated, with a lot of lively informal chats about science.

With this event, we adapted for the first time to a new hybrid format. Apart from the 100 participants attending in person, we also had around 70 virtual participants logging on to our virtual platform. Hybrid events open up participation to a broader group of people that otherwise would not have been able to attend due to lack of resources, busy schedules or difficulties travelling across the world. But like everything new, it also brings challenges. For us, that means trying to integrate things like poster sessions and networking sessions into the virtual event. So, we accept the challenge and look forward to welcoming more scientists to our events, both onsite and virtually.

Raili: “I am looking forward to my next hybrid event to bring together scientists from across the world. Build up my knowledge organising hybrid events with new ways of interaction and exploring more opportunities to create virtual options for in-person events.”

Group photo Biological oscillators, photo by Stuart Ingham/EMBL

The EMBO|EMBL Symposium ‘Biological oscillators: design mechanism and function’ took place 6 – 9 March 2022 at EMBL Heidelberg.

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Poster prize winners of ‘Biological oscillators: design, mechanism and function’

A buzzing helix at The Advanced Training Centre. Scientists holding a beer or a soft drink, pointing at the poster, discussing, laughing. It might have been a bit awkward initially, but soon enough it felt like the old days. And not only was it fun to be around peers again, but the organisers were also highly pleased with the exceptional quality of the posters.

Out of 107 onsite participants and 52 posters, four won an award for best poster by popular vote. We would like to introduce to you the winners and their research:

  1. Katharina Sonnen / Sonja Weterings, Hubrecht Institute, the Netherlands
  2. Victoria Mochulska, McGill University, Canada
  3. Laurent Jutras-Dubé, McGill University, Canada & Joshua Hawley,  the University of Manchester, UK

Signaling dynamics in the homeostasis of the small intestine

Sonja Weterings / Katharina Sonnen, Hubrecht Institute, the Netherlands

Sonja Weterings, Hubrecht Institute

Abstract:

How information is transmitted between cells to govern development and tissue homeostasis in time and space remains a central question in biology. In particular, the role of signaling dynamics in this control is still largely unknown. While signalling dynamics during embryonic development have been studied extensively, such as in the control of mesoderm segmentation, the role of signalling dynamics in adult tissue is less well
understood. In the small intestine, a network of multiple signalling pathways coordinates homeostasis of the tissue. Here, I will present our latest findings on signalling dynamics in
the small intestine.

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Modelling the entrainment response of the somite segmentation clock

Victoria Mochulska, McGill University

Victoria Mochulska, McGill University

Abstract

In this study, a coarse-graining, entrainment approach is used to gain new insights into the dynamic properties of vertebrate segmentation clock from dynamical systems perspective. We entrain the mouse segmentation clock to various periods and extract information about the dynamic phase-locking behaviour, including the range of entrainment periods, entrainment phase, and the convergence route towards the entrainment phase. Using the entrainment quantification data, we derive the segmentation clock phase response curve (PRC). The inference of the PRC reveals two properties: a highly asymmetrical, mainly negative PRC, and an adjustment of the intrinsic period during entrainment.
We next construct a minimal model of the segmentation clock. We build upon the simplest non-linear phase oscillator, the classical Radial Isochron Cycle (RIC). We perturb it into an Elliptic Radial Isochron Cycle with Acceleration or ERICA. We then use Monte Carlo optimization to find parameters best fitting the experimental PRC. The results from this
optimization put the oscillator far from the standard RIC.
From the optimized ERICA model, we derive numerically the Arnold tongues of the system and the phase/detuning curves for all entrainment parameters. We correctly capture the entrainment range and the unusual sigmoidal shape of the entrainment phase as a function
of entrainment period. Our minimal model thus captures all the essential features of the segmentation clock during entrainment and reveals its underlying dynamical properties.
Combined, this coarse-grained theoretical-experimental approach reveals how we can derive simple, essential features of a highly complex dynamical system and hereby provides precise experimental control over the pace and rhythm of the somite segmentation clock.

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Or read the publication

Dynamic switching of lateral inhibition spatial patterns

Joshua Hawley, the University of Manchester

Abstract

Notch-Delta signalling, which forms a lateral inhibition loop between cells in direct contact, typically generates a population of alternating high and low expression. However, HES5 which is a downstream target of Notch has been found to exhibit interesting non-stationary spatial patterning of similarly expressing clusters of cells in the developing neural tube (Biga
et al., 2021; Manning et al., 2019). Theses clusters organise into an average spatial repetion of higher and lower expression every 3-4 cells, and crucially do not form stationary patterns over time, instead the peaks and troughs persist for an average of 6-8 hours before switching states (high-to-low or low-to-high) (Biga et al., 2021)
Our initial investigation into how the dynamic spatial pattern might be generated started by adapting a previously parameterised single-cell HES5 model (Manning et al., 2019) to a multicellular model, whereby HES5 dynamics are coupled between cells by a lateral inhibition Hill function. With this relatively simple model, we found that intermittent
coordination of neighbouring HES5 dynamics emerges from time-delayed Notch-Delta interactions, but that this model did not explain the regular switching (every 6-8 hours) and only infrequently formed spatial patterns of 3-4 cells. We are now building on this modelling work, focussing on additional mechanisms that generate dynamic switching and longer spatial periods. Specifically, we perform explorations of gradient-induced travelling waves inspired by somitogenesis studies (Sonnen et al.,
2021) the inclusion of protrusions to extend interaction distance between cells consistent with recent reports from (Hadjivasiliou et al., 2016), as well as investigating how perturbation from altered Notch signalling, cell cycle, or cell movement may enable the regular switching
between high and low expression. Overall this work aims to understand the function of this type of dynamic patterning in the context of differentiation decisions both spatially and temporally.

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Rectified Kuramoto synchronization in an embryonic oscillator ensemble

Laurent Jutras-Dubé, McGill University, Canada

Laurent Jutras-Dubé, McGill University

Abstract

During vertebrate embryo development, presomitic mesoderm (PSM) cells tightly synchronize their genetic oscillations in time and space to form somites. To model this synchronization process, early theoretical studies, as well as recent studies combining experimental observations and numerical simulations, have used the framework of coupled
phase oscillators. To represent the coupling of these phase oscillators, most studies employ the Kuramoto model, which predicts that two coupled oscillators will reach the average phase as they synchronize, a phenomenon called phase averaging. With the aim of testing this prediction, we develop a novel experimental assay to culture mouse PSM cells that are stably oscillating for an extended period of time, with a narrow period distribution and a wide phase distribution. Our experimental evidence is in disagreement with the Kuramoto model’s phase averaging prediction. To explain the observed coupling dynamics, we devise a new synchronization model, the rectified Kuramoto model. We extract predictions from our model and verify them with our experimental assay. Thus, we propose our rectified Kuramoto model as the best current alternative to the Kuramoto model, which we falsified, at least for mouse tailbud cells.

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Biological oscillators: design, mechanism and function took place at EMBL Heidelberg from  6–9 March 2022

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Best Poster Flash Talk winners of the Mobile Genome

This year, the virtual EMBO Workshop: “the Mobile Genome: Genetic and Physiological Impacts of Transposable Elements” centered around the broad impacts of TEs on organismal biology. It turned out to be a diverse meeting with interesting cross-disciplinary discussions, assembling experts from diverse fields including genomics, epigenetics, structural biology, developmental biology, immunology, cancer biology and neurobiology.

Over 90 posters were available on the virtual platform and three presenters stood out with their poster flash talks. An extraordinary accomplishment in the virtual format. With no further ado, we are introducing the winners and their research!

The repressive SCAN zinc-finger protein family targets transposable elements

Presenter: Wayo Matsushima

Wayo Matsushima, École Polytechnique Fédérale de Lausanne, Switzerland 
Wayo Matsushima, École Polytechnique Fédérale de Lausanne, Switzerland

Abstract

Transposable elements (TEs) contribute to genome innovations through insertions of coding and non-coding elements. KRAB zinc-finger proteins (KZFPs) function as sequence-specific repressors by recruiting KAP1/TRIM28, a scaffold protein of a heterochromatin-inducing complex, to TE-derived sequences. An ancestral KZFP gave rise to another family of transcription factors through the exonisation of the gag gene from the Gmr1-like transposon family as the SCAN domain. This SCAN zinc-finger protein (SZFP) family experienced multiple rounds of segmental duplication events, resulting in the presence of ~300 family members in diverse amniote genomes. Despite its abundance and evolutionary proximity to KZFPs, the functions of the SZFP family are still not well understood.

To analyse evolutionary conservation of SZFPs, we compared the DNA-contacting zinc-finger amino acid sequences of the human SZFPs to those of 65 other amniote species. This revealed that the zinc finger signatures of SZFPs are under rapid lineage-specific selection, and that several human SZFPs harbour primate-specific zinc finger sequences.

To characterise the genomic targets of all of the 55 human SZFPs, we performed ChIP-seq on 293T cell lines, each expressing one of the SZFPs with an HA-tag. We found that the binding sites of a number of SZFPs significantly overlap with specific TE subfamilies, and further observed that the evolutionary ages of SZFPs and their TE targets often matched, suggesting the TE-driven positive selection of this transcription factor family.

We next performed luciferase assays to study the regulatory function of SZFPs. We discovered that SZFPs act as transcriptional repressors owing to their SCAN domain with its conserved C-flanking 15 amino acid residues. Similar levels of repression were obtained in KAP1/TRIM28 knockout cells, demonstrating that, in contrast to KZFPs, SZFPs act independently of this master corepressor.

Together, this study identifies SZFPs as putative controllers of the regulatory potential of TEs, through their lineage-specific zinc finger repertoire and the repressive domain derived from the co-opted retroviral gene. Future work will explore the potential impact of SZFPs and their TE targets on species-specific gene regulatory networks.

The poster contains unpublished data and can therefore not be published. Follow Wayo Matsushima on Twitter for more information on his projects.

A natural transposon affects gene regulation and fitness related traits depending on the developmental stage and environmental conditions in D. melanogaster

Presenter: Miriam Merenciano

Miriam Merenciano, Institute of Evolutionary Biology (CSIC-UPF), Spain

Abstract

TEs have been considered a genome-wide source of regulatory elements capable of regulating nearby gene expression. In Drosophila melanogaster, the FBti0019985 natural TE insertion has been previously reported to add a transcription start site to the Lime transcription factor. In this work, we performed invivo enhancer assays and gene expression analysis with CRISPR/Cas9 mutants and natural populations to explore the effects of FBti0019985 on Lime expression under different stress conditions and different developmental stages. We found that this insertion acts as an enhancer in the adult stage under immune-stress conditions. Indeed, the deletion of predicted immune-related binding sites in the TE significantly reduces its enhancer activity in infected conditions, confirming that it harbors functional cis-regulatory elements. We also found that the TE upregulates Lime in embryos, however, in this case we could not pinpoint the molecular mechanism. Finally, we found that TE-induced Lime upregulation was associated with tolerance to bacterial infection and with increased egg-to-adult viability. Our results suggest that different developmental stages and environmental conditions should be tested in order to fully characterize the molecular and functional effects of a genetic variant.

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An ATPase filament bridge: How a transposon and CRISPR stick together

Presenter: Irma Querques

Irma Querques, University of Zurich, Switzerland

Since the discovery of bacterial adaptive immunity, CRISPR-Cas systems have been mainly regarded as a mechanism to counteract horizontal transfer of mobile genetic elements including transposons in prokaryotic genomes. Conversely, a distinct family of Tn7-like elements co-opted CRISPR-Cas RNA-guided machineries to direct transposon insertion into specific target sites. In type V CRISPR-associated transposons, RNA-directed transposition relies on the cross-talk between the pseudonuclease Cas12k, the transposase TnsB, the zinc-finger protein TniQ and the ATPase TnsC. Yet, the molecular mechanisms underpinning this interplay have remained unknown. Here we present a cryo-electron microscopy structure of DNA-associated TnsC in its ATP-bound state. The structure reveals that the AAA+ ATPase forms an ATP-dependent helical filament that encloses and remodels the underlying target DNA. One strand only of the duplex is tracked by consecutive TnsC protomers with an unexpected two-nucleotide periodicity, resulting in a DNA helix with 12 base pairs per turn. Biochemical studies show that TnsC polymerization is a critical aspect of the system that enables the coupling of RNA-guided target recognition by Cas12k with the downstream recruitment of TnsB by direct protein interactions. In turn, TnsB triggers filament disassembly upon ATP hydrolysis, establishing target immunity. We also show that TniQ directly interacts with TnsC, restricting its polymerization. A crystal structure of TniQ reveals structural diversity within the TniQ protein superfamily, further suggesting a role in TnsC regulation rather than DNA targeting. Together, our data point to a mechanistic model whereby TnsC oligomers bridge between the RNA-guided target selector Cas12k and the transpososome, promoting target DNA remodeling and ultimately transposon integration. This work discloses first mechanistic insights into targeting and regulation of type V CRISPR-associated elements and will guide the rational design of these systems as programmable, site-specific gene insertion tools.

View the poster

The EMBO Workshop: “The Mobile Genome: Genetic and Physiological Impacts of Transposable Elements” took place from 29 August – 1 September 2021. 

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Record attendance at New Approaches and Concepts in Microbiology

Written by event reporter Magdalena Wutkowska.

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.

A table with a laptop, a thermos with coffee or tea and a notebook on a desk.
My setup for the symposium

Pre-symposium sessions

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.

Scientific sessions

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?

Unexpected perks of attending online meetings from a favourite place!

This blogpost was written by Magdalena Wutkowka, Postdoc in Anne Daebeler’s Group, Soil and Water Research Infrastructure, Biology Centre CAS, České Budějovice (CZ).

Learn more on how to become an event reporter for EMBL Events.

 

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Zooming into the PhD Symposium: “It’s about different scales of life, and not even just life on earth.”

Each year, a bunch of PhD students from EMBL join forces to organise a large symposium for their fellow PhD students across the globe. This year’s (virtual) PhD symposium is the 23rd of its kind. The Big Picture: Zooming into Life is taking place from 16 -17 December.

Around 30 first year PhD students are part of the organising committee for the symposium. Amandine and Dewi, both in Heidelberg, are two of the main organisers. Amandine is a joint PhD student at the University of Heidelberg (Kuner lab) and EMBL (Alexandrov lab)  on neuroinvasive cancer, and Dewi is working at EMBL in the Steinmetz lab, where she is working on developing a CRISPR/Cas9 screen in primary immune cells.

Dewi Moonen
Amandine Prats

How did the team come up with the theme of this symposium?

Amandine: “We wanted to have an interdisciplinary topic that is interesting for a lot of people. We all have such different research backgrounds, but it should be interesting for everyone. We tried to include more than just biology.”

Dewi: “I really like that this topic is about different scales of life, and not even just life on earth, we also have a talk about astrobiology.”

Amandine: “It is a very broad topic, but the talks themselves are not general. They are accessible, but they will be in-depth and connected to the bigger picture at the same time. We are hoping the talks will spark ideas and new collaborations.”

What are you personally excited about?

Dewi: “For the talks, amongst others, I am looking forward to Christoph Bock. His group performs interdisciplinary research at the interface of immunology, cancer and precision medicine, and develops new technologies to support this. This technology development is especially an interest of mine.”

Amandine: “We selected really great speakers for this symposium. Not just because of the research topics, but also because they are really good at giving talks. I am very enthusiastic about the astrobiologist Dr. Lynn Rothschild. It is not my field at all, and I never thought about it before, but I am very curious to find out more about bringing life to other planets.”

You are calling for abstracts for short talks and posters. What topics are you looking for?

Dewi: “This symposium is really made by and for PhD students, so we are giving PhD students the opportunity to share their research. We will have a virtual poster session and selected short talks, divided into different categories. It can be about any topic related to life science, but it would be great if you are able to place your research into the bigger picture.”

Can you tell us a little bit more about the programme elements?

Dewi: “We want the symposium to be interactive, so besides the talks, we are organising different workshops and social activities, like virtual lunches and coffee breaks. Because the organisers are all PhD students, the workshops reflect our interests. We have a career workshop and a scientific workshop on imaging. We also have a workshop on mental health that I am looking very much forward to.”

Amandine: “With regard to the workshop on mental health: it can be hard being a PhD-student, as we can be under a lot of stress. Not just due to the current pandemic, but also just in general. The pandemic just made it more visible.”

What was your experience with organising this virtual symposium?

Amandine: “In the beginning, we had to figure out a lot. Most of us have never met each other in real life due to the pandemic. We’ve never organised a large-scale event like this before. But it feels really good now that it is all coming together.”

Dewi: “I think working together in teams is going really well. We have eight different committees, but there is also overlap between them, so we stay connected and up to date.”

A group picture taken on Zoom, with the organisers of this years PhD Symposium. Around 20 people are on screen, with the visual of the symposium as their background.
The PhD Symposium Organising Committee

You have put a lot of effort and time into organising this symposium. When do you think it will be a success?

Dewi: “For me, it will be a success if the participants are actively engaged, and not just having their computers open and listening to the talks. We want to organise a truly interactive meeting.”  

Amandine: “I am hoping that people will talk to each other and make some longer-term connections, and maybe even collaborations.” 

The Big Picture – Zooming into Life takes place on 16 – 17 December 2021.
Submit your abstract by 10 October. 

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