‘From Functional Genomics to Systems Biology’ shines virtually

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.

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Meet the EMBL Events Team: Raili Pall

In the middle of 2020, Raili Pall joined the Course and Conference Office (CCO) team. She was the first member to start working with us remotely and it was quite a journey to get everything in place. Despite all this, she was a total hero, learned everything so quickly and started talking the CCO “language” (yeah, we kind of talk in codes for our events) within a few weeks!

Check out her interview to the end, you might want to read her favourite book🙂.

Railli Pall PHOTO: Railli Pall

At EMBL since: June 2020
Number of organised conferences/courses: 4

Favourite place in Heidelberg: 
Altstadt (Old Town). I find it really cute, full of nice cafés and restaurants.

Old Town Heidelberg Marktplatz (2017). PHOTO Achim Mende/Heidelberg Marketing GmbH

First thing you do before a conference/course starts and first thing you do after it finishes:
Before the conference/course starts I’ll go through my checklist to be sure I didn’t forget anything. After a conference/course finishes I say a big thank you to the scientific organisers, speakers and the participants for making it all possible.

What are the challenges/differences of organising a virtual conference or course?
The most challenging is probably the social aspect – working out how to increase the audience interaction and keep them engaged during the virtual event.

What do you miss most about life before the pandemic?
Travelling. I love travelling and discovering new cultures, food and people. I can’t wait to start planning some trips & travel as soon as it’s safe again.

If you weren’t an event organiser, what would you be?
I’d love to be an interior designer. I can spend hours in design shops and reading design & décor magazines. I find it incredible how simple elements can change the look and feel of a space.

If you were a superhero, what power would you like to have?
I would like my superpower to be able to speak all the languages in the world. I find languages fascinating and it would be amazing to be able to communicate with anyone in their language.

Favourite:
Recipe: I love Indian food, so I’d probably choose butter chicken. I recently learned how to cook it myself and am very proud of it😊 .

Book: „On nagu pole“ (“It is like it isn’t”) by Estonian author Alan Adojaan. I read it quite long time ago, but it’s one of the most funny and inspiring travel-books I’ve ever read.

Film: I love to watch movies, so it’s difficult to choose one. I like Paolo Sorrentino (‘La Grande Bellezza’, ‘Youth’, ‘Loro’) and Quentin Tarantino movies. One of the recent highlights was ‘Parasite’ by Bong Joon-ho that I finally managed to watch.

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Best Poster Awards – In Situ Structural Biology Workshop

The EMBO Workshop: In Situ Structural Biology: From Cryo-EM to Integrative Modelling was our final virtual conference of 2020, but there was no trace of Zoom fatigue amongst the 466 participants who joined us from 6 – 8 December!

80 international researchers presented their posters during the two posters sessions on the following topics:

  • Biophysical analysis in cells
  • COVID-19
  • Imaging across scales
  • Integrative modelling
  • Molecular sociology
  • Structural analysis in situ
  • Structural biology

Each of the participants had the chance to vote for their favourite poster, resulting in two posters winning the Best Poster Award kindly sponsored by EMBO Press.  Here are the winners:

New insights on the catalytic mechanism of arsenite oxidase

PHOTO: Filipa Engrola

Authors: Filipa Engrola, Márcia Correia, Teresa Santos-Silva, Maria Romao, (UCIBIO@FCT-NOVA, Portugal)

Arsenic (As) and antimony (Sb) are two metalloids that, due to anthropogenic and natural causes, pose an environmental  threat, considered as priority pollutants by the World Health Organisation and the United States Environmental Protection Agency. Although the safety guards recommend a maximum of 10 μg/L of As and Sb in drinking water, these values are exceeded in many regions worldwide, with no remediation approach that is simultaneously effective, clean and economically sustainable [1,2]. The ancient bioenergetic enzyme arsenite oxidase (Aio), from microorganisms Rhizobium sp. NT-26 (NT-26 Aio) and Alcaligenes faecalis (A.f. Aio), is currently being studied for its use as a biosensor and in bioremediation processes. Both Aio enzymes contain a large subunit (AioA) that harbours a molybdenum centre and a [3Fe-4S] cluster, and a small subunit (AioB) that possess a Rieske [2Fe-2S] cluster and have demonstrated to oxidise AsIII, as well as SbIII, into the easier to remove and less toxic forms of AsV and SbV, respectively [3,4]. Aiming to elucidate the catalysis mechanism of the enzymes, a combination of expression and purification of the proteins, crystallisation, structural analysis, enzyme kinetics and affinity tests were conducted. X-ray structures of the ligand-free form of the enzyme had been previously determined (PDB: 4AAY, 5NQD and 1G8K [3,5,6]). In our work, Aio crystals in complex with two different forms of the substrate analogue – Sb oxyanions, with a reaction kinetic 6500 times slower than AsIII [6] – diffracted up to ca 1.8 Å resolution. The structures show the reaction intermediates bound at the active site, with a μ-oxo bridge binding Sb to the Mo atom. Analysis of bond lengths and geometry of the ligands at the Mo active site allowed us to revisit the catalytic mechanism of As oxidation [7], contributing to the understanding and future biotechnological application of this family of enzymes in water treatment.

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Allosteric hotspot in the main protease of SARS-CoV-2

PHOTO: Léonie Ströhmich

Authors: Léonie Strömich, Sophia N Yaliraki, (Imperial College London, UK)

Since the beginning of 2020 we have seen the coronavirus SARS-CoV-2 causing a global pandemic with almost 34 million cases and over 1 million deaths worldwide [as of 01.10.2020] [1.] As a result, we have seen a surge in research efforts to develop effective treatments for the underlying disease, COVID-19. One approach is to target the main protease (Mpro) of SARS-CoV-2 as it is essential for virus replication in an early step of the viral life cycle [2.] Most efforts are centred on inhibiting the orthosteric binding site of the enzyme. However, considering allosteric sites on the protein allows for more selective drug design and widens the chemical search space. Here, we report an allosteric hotspot in the SARS-CoV-2 Mpro dimer by using novel atomistic graph theoretical methods: Markov transient analyses follow the propagation of a random walker on a graph and have been shown to successfully identify allosteric communication in catalytic proteins [3.] We further score the so identified allosteric hotspots against random sites in similar distances and thus identify a statistically significant putative allosteric site in the SARS-CoV-2 Mpro. We then simulate a binding event at this hotspot region using data from a recent XChem fragment screen by the Diamond Light Source [4.] which provides a starting point for rational drug design. This study uses highly efficient network theoretical models to shed light on allosteric communication and uncovers putative allosteric sites in the SARS-CoV-2 main protease. This provides a valuable contribution to the ongoing efforts to find a cure against COVID-19 by broadening the horizon for drug discovery efforts.

Image: Léonie Ströhmich

References:
[1.] Official World Health Organization COVID-19
dashboard: https://covid19.who.int (Accessed: 01.10.2020).
[2.] Hilgenfeld, R. (2014). FEBS Journal, 281(18), 4085-4096.
[3.] Amor, B., Yaliraki, S. N., Woscholski, R., & Barahona, M. (2014) Molecular BioSystems, 10(8), 2247-2258.
[4.] Douangamath, A., Fearon, D., Gehrtz, P., Krojer, T., Lukacik, P., Owen, C. D., … Walsh, M. A. (2020) Nature Communications, 11, 5047.

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Working on your own conference poster? Then check out these 8 tips for preparing a digital poster that stands out from the crowd.

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