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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Best Poster Awards – EMBO|EMBL Symposium: Organoids 2020

The recent virtual EMBO|EMBL Symposium on Organ Development and Disease in 3D Culture saw the highest number of registrations we have had since we launched the format. A total of 880 researchers from around the world got together online to discuss recent developments in the formation and maintenance of organoids and their use in disease studies and regenerative medicine.

Out of the 200 digital posters that were presented at the three poster sessions, four were distinguished with a poster prize by a committee appointed by the scientific organisers. Here are the winners:

Organoids model transcriptional hallmarks of oncogenic KRAS activation in lung epithelial progenitor cells

PHOTO: Antonella Dost

Authors: Aaron Moye (1), Antonella Dost (1), Marall Vedaie (2), Linh Tran (5), Eileen Fung (5), Dar Heinze (2), Carlos Villacorta-Martin (2), Jessie Huang (2), Ryan Hekman (2), Julian Kwan Kwan (2), Benjamin Blum (2), Sharon Louie (1), Sam Rowbotham (1), Julio Sainz de Aja (1), Mary Piper (4), Preetida Bhetariya (4), Roderick Bronson (3), Andrew Emili (2), Gustavo Mostoslavsky (2), Gregory Fishbein (5), William Wallace (5), Kostyantyn Krysan (5), Steven Dubinett (5), Jane Yanagawa (5), Darrell Kotton (2), Carla Kim (1)

Presenter: Antonella Dost (1)

Mutant KRAS is the most common oncogenic driver of epithelial cancers. Nevertheless, the molecular changes induced by KRAS activation in primary epithelial cells beyond activation of proliferation remain elusive. Here, we determined transcriptional changes at single-cell resolution after KRAS activation in distal lung epithelial cell populations. We developed a new in vitro organoid system to define the early oncogenic KRAS transcriptional program and model early-stage lung adenocarcinoma (LUAD) using primary murine lung cells. Alveolar epithelial progenitor (AT2) cells expressing oncogenic KRAS lost their mature identity and acquired a transcriptional program similar to lung development and progenitor cells. Similar changes were observed in an early-stage LUAD mouse model, in human induced pluripotent stem cell derived AT2 cells, and in stage I lung cancer patient samples, validating our organoid model. While these events have been observed in advanced lung cancers in mice and humans, we show that KRAS induced dedifferentiation occurs in early-stage lung cancer. This work provides a new organoid tool to rapidly recapitulate lung cancer progression in vitro and a window into the transcriptional changes that immediately follow oncogenic KRAS expression in epithelial cells, revealing candidate targets for early intervention of KRAS-driven lung cancer.

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View related paper

(1) Boston Children’s Hospital, United States of America
(2) Boston University, United States of America
(3) Harvard Medical School, United States of America
(4) Harvard T. C. Chan School of Public Health, United States of America
(5) University of California Los Angeles, United States of America


Using human pluripotent stem cell-derived organoids to investigate regional-specific features of the small intestine

PHOTO: Guillermo Sanchez

Authors: J Guillermo Sanchez, Heather McCauley, Jacob Enriquez, James Wells, Cincinnati Children’s Hospital, United States of America

Presenter: J Guillermo Sanchez

The gastrointestinal tract is the largest endocrine organ in the body. Specialised nutrient sensing cells, called enteroendocrine cells, are embedded in the intestinal epithelium and secrete over 20 hormones that regulate processes such as satiety, gut motility and gastric emptying. Directed differentiation of human pluripotent stem cells into human intestinal organoids has been used to study and mimic intestinal development; however, most of these models generate intestinal tissue which resembles duodenum and proximal jejunum (Spence, et al 2011). The intestine displays distinct regional functions along the proximal-distal axis, with the ileum being important for unique enteroendocrine hormone secretion, bile acid resorption and interactions with the microbiome. It is known that major signaling pathways such as Wnt, FGF and BMP can affect the regional identity of the developing GI tract. Consistent with previous studies (Munera, Tsai) we found that manipulation of the exposure time of intestinal spheroids to these signaling pathways generated distal intestinal tissue by expression of epithelial markers, nutrient transporters, and hormone expression. These distally-patterned human intestinal organoids retain their regional identity after transplantation in vivo, and can be used to generate epithelial-only enteroid cultures. It remains unknown how diverse cellular types and functions are established along the proximal-distal axis of the small intestine. This model enables us to compare the early transcriptional changes involved in conferring regional-specific features, including enteroendocrine cell allocation, to the GI tract.

Poster currently not available


Recapitulating the somitogenesis in vitro to identify novel causative genes for congenital bone diseases

PHOTO: Marina Matsumiya

Authors: Marina Matsumiya (1), Mitsuhiro Matsuda (1), Nao Otomo (2), Yoshiro Yonezawa (2), Shiro Ikegawa (2), Miki Ebisuya (1)

Presenter: Marina Matsumiya

Somites are periodically formed though the segmentation of anterior parts of presomitic mesoderm (PSM) in embryos. This periodicity is controlled by the segmentation clock gene Hes7, which exhibits a wave-like oscillatory expression in the PSM. The periodical somite formation is a crucial event for body segment formation and abnormal somitogenesis leads to congenital bone diseases.

Spondylocostal dysostosis (SCD) is a bone malformation disease which is characterised by morphological abnormalities of vertebrae and ribs. Mutations in several somitogenesis-related genes, including HES7, are already known as the cause of SCD. As for 75% of SCD patients, however, the causative gene and at what stage of bone development the abnormality occurs are still unclear.

Thus, the aim of this study is to establish a method to recapitulate the somitogenesis in vitro and to identify novel a causative gene of SCD.

To recapitulate the somitogenesis in vitro, we previously reported a simple and efficient method to generate mouse embryonic stem (ES) cell-derived PSM-like tissues (Matsumiya et al., Development, 2018). In these tissues, Hes7 oscillation was synchronized among neighboring cells, the anterior-posterior axis was self-organised, and somite-like structures were observed. We are currently developing a similar method to recapitulate the human somitogenesis by using human induced pluripotent stem (iPS) cells instead mouse ES cells. Furthermore, by using human iPS cell lines that lack the candidate gene of SCD for the in vitro somitogenesis, we are trying to identify a novel causative gene of SCD.

Poster currently not available

(1) EMBL Barcelona, Spain
(2) RIKEN Center for Integrative Medical Sciences, Japan


Heme oxygenase 1 upregulation is induced by stress via alpha-synuclein aggregation in transgenic mice and in Parkinson’s disease derived brain organoids

PHOTO: Silke Frahm-Barske

Authors: Silke Frahm-Barske (2), Sebastian Diecke (2), Franz Theuring (1)

Presenter: Silke Frahm-Barske

Excessive accumulation of alpha-synuclein (a-syn) predisposes to the development of Parkinson’s disease (PD), a disorder characterised by neurodegeneration in the substantia nigra and concomitant motor impairments. It was previously shown that stress-induced release of glucocorticoids accelerates the progression of PD and that the glucocorticoid receptor (GR) is downregulated in several neurodegenerative as well as in stress-related diseases. The impact of altered a-syn protein levels on GR dysfunction and stress-related protein expression is largely unexplored, but may have severe implications for PD manifestation and disease progression. Therefore, we examined the effect of chronic stress in two models overexpressing human a-syn: a transgenic mouse model (h-a-synL62) and brain organoids derived from iPSCs of a PD patient. Wildtype mice that underwent daily restraint for 6 weeks presented typical chronic stress induced features, such as GR-deficiency and increased a-syn protein levels in prefrontal cortex and hippocampus. Importantly, these molecular alterations were reproduced in forebrain organoids generated from healthy donors after treatment with the synthetic glucocorticoid Dexamethasone for 2 weeks. In contrast, glucocorticoid exposure had no effect on GR expression and normalised the level of a-syn in h-a-synL62 mice and PD brain organoids. Accordingly, heme oxygenase 1 (HO-1), an antioxidant protein that can be induced by soluble oligomers and protofibrils and that triggers proteosomal degradation of a-syn, was upregulated. Together, our work provides a new link between a-syn overexpression, GR-deficiency and oxidative stress and their contribution to the development and progression of PD. Further, we established and validated a human 3D tissue culture model that can be used to study stress related diseases, offering replacement of research animals exposed to disturbing procedures.

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(1) Charité – University Medicine Berlin, Germany
(2) Max-Delbrück-Center, Germany


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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EMBL’s Corporate Partnership Programme celebrates 10 years of impact

As EMBL’s Advanced Training Centre passes its 10th anniversary, Corporate Partnership Manager Jonathan Rothblatt reflects on the ATC Corporate Partnership Programme and how it promotes training for outstanding scientists.

Jonathan Rothblatt, Corporate Partnership Manager at EMBL. PHOTO: Jonathan Rothblatt

Since its opening in March 2010, the EMBL Advanced Training Centre (ATC) has served as a forum for the scientific exchange of new ideas, data, approaches and tools. An important component of this is the ATC Corporate Partnership Programme (CPP), which aims to connect companies with the latest developments in molecular biology and build successful long-term relationships between EMBL and corporate partners.

EMBL Advanced Training Centre built in 2010. PHOTO: KARL HUBER FOTODESIGN

Supporting outstanding scientists

The support that industry partners provide through their membership in the CPP, ensures that outstanding scientists – from PhD students to established investigators – are not excluded from attending a course or conference, or working in an EMBL laboratory as a visiting scientist, because of a lack of funds to cover conference fees or travel expenses. Since 2010, CPP funding has provided fellowships covering registration fees and travel costs to more than 2,100 participants from over 90 countries, attending more than 350 EMBL or EMBO courses, conferences, or symposia.

In addition to the significant impact of their financial support, the engagement and collaboration of corporate partners is crucial in the development and delivery of EMBL’s courses and conferences. For example, of the 33 training courses held at EMBL Heidelberg in 2019, 11 were co-organised with CPP partners. Another example is the EMBL Conference ‘Expanding the Druggable Proteome with Chemical Biology’, which took place in February 2020. This conference, co-funded by the CPP, explored advances at the interface between academic and industry research. The scientific organisers included two CPP partners alongside academic leaders in the field (read the interview with one of the organisers Gerard Drewes here and check out the winning posters here).

Building mutually beneficial relationships

The strong involvement of EMBL scientists at all levels is another crucial factor in enabling the CPP to establish and develop mutually beneficial relationships with its corporate partners. The alliance of the CPP with its corporate partners is one facet of EMBL’s engagement with industry – in particular the life sciences business sector. This compliments the activities of EMBL’s technology transfer partner EMBLEM, the EMBL Course and Conference Office, the EMBL-EBI Industry Programme, and direct interactions with industry partners by EMBL group and team leaders and heads of core facilities.

With two new partners joining the CPP in 2019 and another already this year, the CPP has grown to 19 members, bringing together EMBL and global leaders in a range of business sectors, including biopharmaceuticals, diagnostics, information technology, research and clinical instrumentation, and laboratory products.

Members of the EMBL ATC Corporate Partnership Programme

We look forward to seeing the programme continue to evolve and grow in future years, always striving to deliver outstanding value and maintain its impact on the future of science.

For further information, contact Jonathan Rothblatt (jonathan.rothblatt@embl.de, +49 6221 387 8799), or visit embl.org/cpp.

This article was originally published in Issue 95 of EMBLetc. magazine.

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How speed networking could work at your next virtual conference

With events going digital, professional training has become increasingly convenient and accessible. While getting the latest scientific research developments from the comfort of your home has never been so easy, sitting alone in front of a screen significantly diminishes the chances of meeting new people and collaborators – a benefit of on-site meetings that is considered one of their most important assets.

Most meeting organisers realise that and offer various networking opportunities and socialising incentives as part of the programme. One of the methods we have implemented to facilitate social interaction at our onsite as well as virtual conferences is the so-called speed networking – a networking session where people swap conversational partners every 5 minutes with the aim to meet as many people as possible and exchange information about their research or the project they are currently working on. The session is normally scheduled  for the first day of the conference so that participants can later go back to the people they have met during the speed networking session and continue the discussion.

What should you talk about during the speed networking?

5 minutes doesn’t seem like a long time, so it is important that you focus on the essentials. Start by introducing yourself then go into more detail. Are you looking for collaborators? Or maybe a new job or a postdoc position?

How can you do that in just 5 minutes?

  • Prepare a 20 second blurb about yourself
  • Keep aware of the time factor – there should be a countdown on your screen
  • Stick to the vitals
  • Make sure to take notes next to their name so that you can later go back to them for reference
  • Most importantly, have fun and relax! 🙂

What if you don’t finish your conversation within the allocated time slot?

  • Before the time is up, make sure you suggest the next step
  • Message them directly on the available discussion platform with a suggestion for a follow-up meeting
  • After the meeting, be sure to e-mail them with a suggestion for further exchange.

Why not check out our list of upcoming virtual events to see where you can try out your speed networking skills!


For tips on how to do speed networking at onsite events, check out this video.

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How to turn your conference into a virtual event

The current pandemic has forced many event organisers to freeze all ongoing projects with no end date in sight. The impact on the events industry has been dramatic, but it has also provided the opportunity to rethink how we do events and explore other avenues such as virtual conferencing. 

The EMBL Course and Conference Office has just successfully completed its first virtual conferencewhich we managed to put together within a couple of weeks with the tireless work of the scientific organisers, the EMBL IT and AV teams. It has been an interesting experience, not without hiccups of course, but we have learned a lot and are looking forward to applying those learnings to our next online event in May. 

We are happy to share with you some of the steps we followed to quickly turn an onsite conference into a virtual format and how we dealt with the challenges we were faced with.

Commit all your speakers

Once it was clear we were going to try to go virtual with this event, we had to make sure we had all the invited speakers on board to be able to pull together a high-quality programme. Of course, not all of them could join, but if you manage to get the majority of the originally planned speakers, you are good to go!

Explore the technical limitations

One critical thing of course is the technical setup that needs to be tested and working properly during the conference. If you have a dedicated IT and AV team, you are in a good position, as they will be the supporting pillars of your virtual conference. Involve them early on, as they can best advise on and set up the streaming platform. Also, should there be any unexpected technical problems, they will be able to fix those quickly or come up with a working alternative.

Behind the Scenes: The AV team getting ready for the virtual conference.

For instance, in our recent virtual conference, the server crashed due to an automatically scheduled password change on the EMBL media site (talk about bad timing!), and it was only thanks to our great AV team that we managed to migrate the conference to a new platform (Zoom) within the hour.  The programme was adjusted accordingly to accommodate the break and things ran smoothly from then on.

Define the programme

Now that you have the speakers and the software established, it is time to consider the programme. Originally, you would have had 2 or 3 days full of talks with the occasional coffee break and meals in between. However, in a virtual event, it is just not possible to do that. When you define your programme, ask yourself “How long would you sit and listen to online talks?”. Probably not longer than 3-4 hours, so consider this when assigning the speaker slots.

Make it widely accessible

Ideally, your choice of timing of the programme would cover at least 2 time zones so that more participants can join in (e.g. start in the afternoon for CET, which would be morning for ET). For participants in other time zones, you could consider recording and streaming the talks on-demand.

Cover all presentation formats

Live streaming of all talks (invited, short talks and poster presentations) may be what you would expect in an ideal world, but for the reasons we described in the previous two points, it is just not possible. Therefore, in our case, we decided to live stream only the invited talks, while giving the participants the chance to access the pre-recorded short talks and digital posters in a dedicated time slot in the main programme as well as on-demand. Q & A were then taken to the main discussion platform. 

Provide a discussion platform

One of the great benefits of in-person conferences are the peer discussions and networking opportunities which can result in great collaborations and career advancement. 

In a virtual event, these are of course a bit limited, but a dedicated discussion platform outside of the main streaming software can help foster collaborations and knowledge exchange. We chose Slack as the main discussion platform for Q & A which worked very well, but there are many other applications out there that can offer a similar experience.

Involve your sponsors

If you have committed sponsors to support your event, you would want to provide them with opportunities to reach out to the community. Depending on what package they have booked, you can replace the onsite services with online benefits, such as a pre-recorded short talk, a discussion channel, online banners, logo placements or adverts. 

Test, test, test!

Most importantly, before you launch the online conference, make sure to test everything. Schedule test sessions with each of your speakers and chairs to make sure that all works well on their end as well before going live.

Behind the Scenes: The AV team getting ready for the virtual conference.

But remember that even if you follow all the steps and make sure that every tiny detail is thought of, you may still end up having some unexpected problems during the live stream, just as you may encounter difficulties at an onsite event. The truth is that for all of us (both event organisers and participants) this is a new experience from which we can only …

…Learn and improve

For our first virtual conference we are extremely grateful to have received so much constructive feedback that we are currently working on implementing in the future.  Our participants have been amazingly understanding and willing to help us improve. At the end of the day, despite some technical difficulties during this test run, looking at the feedback we realise that we have managed to achieve our goal to connect the community and get the science across.

“Congratulations for organising this very first virtual meeting. It was really great despite some technical issues. It was really good and thus too short.”

“Science and technology help people in good and bad times. This conference was for me a fresh breeze of exciting science and a taste of life normality during forced social distancing. Thanks!”

“The Four-Dimensional Genome EMBL Symposium was great! Many inspiring talks on chromatin & nuclear organization with partially unpublished data. I couldn’t have participated hadn’t it been VIRTUAL: thanks to @EMBLEvents team & all organizers for making it possible!”

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