Best short talk winners at New Approaches and Concepts in Microbiology

The popular symposium “New Approaches and Concepts in Microbiology” took place virtually this year. 598 people from across the globe joined from their own time zone. Two presenters impressed the crowd with their short talks, even though the local time for one of them was 4.50 am (that doesn’t count as morning yet, does it?).

Jordi van Gestel and Nitzan Tal were the well-deserved winners. Read about their research below.

Short-range quorum sensing controls horizontal gene transfer at micron scale in bacterial communities

Jordi van Gestel, University of California, San Francisco, USA

Presenter: Jordi van Gestel, University of California, San Francisco (UCSF), USA

Introduction: I am a Postdoc in the laboratory of Carol Gross at UCSF. Being trained as an evolutionary biologist, I was introduced to the fascinating world of microbiology during my PhD and have been working at the interface of both fields ever since. My research focuses on the organisation and evolution of bacterial cell collectives.

Abstract
Inside bacterial communities, cells often communicate through the release and detection of small diffusible molecules, a process termed quorum-sensing.

In general, signal molecules are thought to broadly diffuse in space; yet, paradoxically, cells often employ quorum-sensing to regulate traits that strictly depend on the local community composition, such as conjugative transfer. This raises the question if and how nearby cells in the community can be detected.

Here, we employ a microfluidic platform to determine how diverse quorum-sensing systems, differing in their regulatory design, impact the range of communication. While some systems indeed support long-range communication, we show that other systems support a novel form of highly localized communication.

In these systems, signal molecules propagate no more than a few microns away from signalling cells, due to the irreversible uptake of these signal molecules from the environment. This enables cells to accurately detect micron scale changes in the community composition and engage in local cell-to-cell communication.

Intriguingly, several mobile genetic elements, including conjugative elements and phages, employ short-range communication to specifically assess the fraction of susceptible host cells in their vicinity and adaptively trigger horizontal gene transfer in response. Our results underscore the complex spatial biology of bacteria, where cells both communicate and interact at widely different spatial scales.

Antiviral defense via nucleotide depletion in bacteria

Nitzan Tal, Department of Molecular Genetics, Weizmann Institute of Science, Israel

Presenter: Nitzan Tal, Department of Molecular Genetics, Weizmann Institute of Science, Israel

Introduction: I am a PhD student in the lab of Professor Rotem Sorek at the Weizmann Institute of Science. For the past few years I’ve been studying the interactions between bacteria and their viruses (bacteriophages), and how both adapt to ever changing conditions in order to survive. My research focuses on identifying novel anti-viral defense systems and on understanding the extremely diverse arsenal of microbial immunity.

Abstract

DNA viruses and retroviruses need to consume large quantities of deoxynucleotides (dNTPs) when replicating within infected cells. The human antiviral factor SAMHD1 takes advantage of this vulnerability in the viral life cycle, and inhibits viral replication by degrading dNTPs into their constituent deoxynucleosides and inorganic phosphate.

In this study, we report that bacteria employ a similar strategy to defend against phage infection. We found a family of defensive dCTP deaminase proteins that, in response to phage infection, convert dCTP into deoxy-uracil nucleotides. A second family of phage resistance genes encode dGTPase enzymes, which degrade dGTP into phosphate-free deoxy-guanosine (dG) and are distant homologs of the human SAMHD1.

Our results show that the defensive proteins completely eliminate the specific deoxynucleotide (either dCTP or dGTP) from the nucleotide pool during phage infection, thus starving the phage of an essential DNA building block and halting its replication. Our study demonstrates that manipulation of the deoxynucleotide pool is a potent antiviral strategy shared by both prokaryotes and eukaryotes.

For tips and tricks on how to give a good scientific talk, watch this video. 

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Best poster awards – BioMalPar XVII

This year,  the BioMalPar conference took place for the 17th time, but the second time virtually. Three poster presenters stunned their peers with their visually attractive digital posters, presentations and research insights. Out of 90 posters, they received the best poster award by popular vote. Meet the winners!

Sex-specific genetic screens identify hundreds of Plasmodium fertility genes essential for the transmission of malaria parasites

Claire Sayers, Umea University, Sweden

Abstract

Sexual reproduction of malaria parasites is essential for their transmission by mosquitoes. Biological processes required for Plasmodium fertility include the formation of gametocytes, their transformation into gametes in response to signals from the mosquito, fertilisation in the bloodmeal, meiosis, and the formation of an invasive ookinete. Stage-specific gene expression data suggest that hundreds of parasite genes are uniquely required for sexual reproduction, but previous gene knockout studies have merely scratched the surface of this important aspect of parasite biology. We have mutagenised P. berghei lines that make only fertile male or only fertile female gametocytes, with barcoded PlasmoGEM vectors to screen >1200 targetable genes for sex-specific phenotypes. Our screens identify hundreds of genes with sex-specific roles. The data recapitulate existing knowledge of Plasmodium fertility and assign functions to previously unannotated genes. For the first time, we are gaining an unbiased picture of the molecular mechanisms of Plasmodium fertility at genome-scale, which will lead to a deeper understanding of this novel biology that could serve as targets for transmission blocking drugs or vaccines.

View Claire Sayers’ poster

ABCI3 confers pleiotropic drug resistance to antimalarial compounds

Emma Carpenter, Wellcome Sanger Institute, UK

Abstract

Understanding the mechanisms available to the malaria parasite for acquiring multidrug resistance will be important for predicting which genes may become important for clinical resistance in the future.
ABC transporters are an important protein family with roles in drug resistance across a variety of organisms, and mutations in PfMDR1 modulate sensitivity to multiple antimalarials. Several other ABC transporters are encoded in the Plasmodium genome, and we have identified mutations in ABCI3 that confer resistance to several experimental antimalarial compounds.
Using in vitro drug selection regimes with a set of four chemically related compounds (SY4, 10, 11, 13), we isolated 12 drug resistant lines that were subjected to whole genome sequencing. All contained either single nucleotide variants (SNVs) or copy number amplifications of abci3. The point mutations were located in or near predicted transmembrane domains, consistent with a role in modifying the substrate specificity of the transporter, and testing of these lines against other compounds chemically-unrelated to the SY series identified a subset to which sensitivity is also affected.

In addition, natural variants of ABCI3 are observed at or near to these putative resistance SNVs, and preliminary evidence indicates differing sensitivities to the SY compounds among field isolates and common lab strains that may be driven by variation in ABCI3.

This work suggests abci3 should be among the genes monitored for changes in prevalence in longitudinal sampling of field isolates.

View  Emma Carpenters’ Poster

Characterization of a new malaria vaccine candidate against Plasmodium vivax using genetically modified rodent malaria parasites

Diana Moita, Instituto de Medicina Molecular JoĂŁo Lobo Antunes, Portugal

Abstract

Malaria, a mosquito-borne disease caused by Plasmodium parasites, is the most prevalent parasitic infection worldwide. Despite considerable efforts, there is still no effective vaccine against human-infective Plasmodium parasites, of which P. falciparum (Pf) and P. vivax (Pv) are the clinically most significant. Whole-sporozoite (Wsp) vaccines, which induce efficient immune responses against the pre-erythrocytic (PE) stages of Plasmodium parasites, are among the most promising immunization strategies so far. Although most malaria vaccine research has focused on Pf infection, Pv continues to be the most widespread of the human-infective Plasmodium species, imposing significant health and economic burdens on affected countries. Importantly, Pv can originate dormant parasitic liver forms – hypnozoites – which may cause malaria relapses long after mosquito transmission. Recently, our lab developed a new Wsp based on the use of transgenic rodent P. berghei (Pb) parasites as a platform to deliver immunogens of human-infective Plasmodium parasites. Since our in silico studies predict that >60% of CD8+ T cell epitopes encoded in both the Pv and Pb proteomes are shared between these two parasites, we generated a new genetically modified Pb expressing the highly immunogenic circumsporozoite (CS) protein from Pv (PvCS), in addition to its endogenous CS, Pb(PvCS@UIS4), to be used as a vaccine candidate against Pv malaria. Our immunofluorescence microscopy studies confirmed that both the endogenous PbCS and the inserted PvCS are expressed during the PE stages of this transgenic parasite, and that its infectivity is similar to that of its wild-type (WT) counterpart. Specifically, the ability of Pb(PvCS@UIS4) to infect Anopheles stephensi mosquitoes, as measured by the number of oocysts or sporozoites formed, as well as its ability to infect and develop normally in mouse hepatocytes and red blood cells showed no significant differences from those observed for WT parasites. Subsequent studies showed that mice immunization with Pb(PvCS@UIS4) elicits the production of anti-PvCS antibodies that efficiently recognize and bind to Pv sporozoites. Considering the lack of efficient strategies to tackle Pv, this study represents a crucial step on the development of a new Wsp vaccine candidate against this parasite.

View Diana Moita’s poster

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Lazy Fur upgrades virtual conference experience with live music

Meet Ira and Tom – a newly-wed couple from Heidelberg and band members of Lazy Fur – a music duo that have been performing live for participants of numerous virtual EMBL conferences and symposia.

Tom and Ira of Lazy Fur. Ira holding a mic, Tom playing the guitar
Tom and Ira of Lazy Fur

“It feels good that we can bring joy and help provide even a better conference experience with a little bit of live music.”

Who is Lazy Fur?

Tom is a Research Staff Scientist in Matthias Hentze’s and Wolfgang Huber’s labs at EMBL Heidelberg and Ira is an executive assistant in a real estate company.

Both of them grew up with music. Ira started singing when she was little and now also plays the piano and bass guitar.

“I used to play the keyboard but discovered my calling as a guitarist in my PostDoc time at EMBL.” Tom shares.

They bonded over their passion for music and started playing acoustic covers of pop and rock songs and singer/songwriter style music. Ira is inspired by Walk Off The Earth, a Canadian group of friends who do spectacular covers of pop songs. And Tom is generally fascinated by buskers in Dublin he met during his PhD.

Virtual concert setup

Virtual conferences are great for many things, but it is very hard to organise entertainment. Lazy Fur found a way to give a live music performance and interact with participants.

Tom had to put in quite some effort to get it right:

“The technical side was quite challenging at first, but now we are very happy that we can provide high-quality streams. We can interact with the viewers who appreciate the live aspect of our performance. ”

What is it like to perform for a virtual audience?

Onsite, you can easily tell which songs the audience likes and if they like the show. In front of a virtual audience, it is more difficult, because you can not see and hear them. Tom and Ira did find a way to interact with the audience.

“The audience can communicate with us either via the YouTube or conference platform chat displayed on the TV in front of us.” Tom says. 

Ira: “We are extremely happy about all the positive responses we got in the chat or comments people sent us after the show.”

Tom: “We have had heart-warming messages from participants about how they enjoyed it. They wrote that this was a very unique and uplifting experience that reminded them of past conferences at the EMBL Heidelberg site.”

And after Covid-19?

Tom: “Performing live is just an amazing experience. EMBL has a great appreciation for live music at their events and it is wonderful to connect with people on that level. So yes, definitely looking forward to that as well!”

Lazy Fur will be performing at the virtual EMBO Workshop: Predicting Evolution, 14 – 16 June 

Check out the website of Lazy Fur
Check the Lazy Fur YouTube channel

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Best Poster Awards: Friend or Foe — Transcription and RNA Meet DNA Replication and Repair

During the second virtual EMBO | EMBL Symposium of the year three scientists were awarded a prize for their scientific poster. In this blog, we present the winners and their research.

Friend or Foe attracted 336 participants worldwide, discussing transcription and RNA and DNA replication and repair in live sessions and panel discussions. Three poster session rounds gave the opportunity for participants to view 72 digital posters and interact with the poster presenters.

After the sessions, a voting round followed and three presenters were distinguished with a best poster award by popular vote.

  1. Gianluca Sigismondo of the German Cancer Research Center in Heidelberg, Germany.
  2. Tycho Mevissen, Howard Hughes Medical Institute and Harvard Medical School, USA
  3. Sara Luzzi, Newcastle University, UK

Read our blog on how to create a prize-winning digital poster.

Chromatin dynamics during DNA repair investigated via chromatin-directed proteomics

A portrait picture of scientist Gianluca Sigismondo
Gianluca Sigismondo, German Cancer Research Center, Germany. PHOTO: Gianluca Sigismondo

Poster presenter: Gianluca Sigismondo

Authors: Gianluca Sigismondo, Lavinia Arseni, Jeroen Krijgsveld

DNA lesions predispose to genomic instability, a hallmark of cancer; therefore cells have evolved repair pathways to solve those harmful insults.

Double-strand breaks (DSBs) represent the most lethal DNA damage first marked by the phosphorylation of the histone H2A.X (ÎłH2A.X) which triggers the recruitment of sensor proteins belonging to either the error-prone non-homologous end joining (NHEJ) or the efficient homologous recombination (HR) pathway.

It is now established that chromatin has an active role also in DNA repair, thus its characterization at DSB repair foci is essential to better understand the coordinate action of the repair mechanisms and to identify novel players participating in tumor-associated apoptotic resistance and cell survival.

Here we dissect chromatin changes upon exposure to ionizing radiations through multiple proteomics-based approaches. We applied the Selective Isolation of Chromatin-Associated Protein strategy (ChIP-SICAP; Rafiee, 2016) to investigate the interactors of core NHEJ, HR proteins and ÎłH2A.X while bound to the DNA or in the chromatin soluble fraction.

Through a click chemistry-assisted procedure we profiled the configuration of DNA-bound proteins during DSBs repair; finally we analyzed the histone post-translational modifications (hPTMs) cross-talk at mono-nucleosomes marked by ÎłH2A.X.

Our integrated analysis identified the dynamics of expected chromatin determinants during the DNA repair and interestingly suggested the role for new candidates specifically enriched upon DSB formation.

Validation experiments based on monitoring of DSB foci formation and resolution in AID-DIvA cells proficient or knock-down cells provided evidence of a role for novel candidates in DNA repair. FACS-based analysis of Traffic-light Reporter (TLR) isogenic cells upon silencing of proteins identified by MS characterized their functional role in NHEJ, HR or pathway choice. Furthermore, we defined hPTMs associated with ÎłH2A.X-marked mono-nucleosomes and their dynamics during DSB resolution.

This analysis corroborated expected enrichments (e.g. H4K20me1/me2) and provided insights on new modifications specifically enriched at ÎłH2A.X-nucleosomes.

Chromatin dynamics during DNA repair investigated via chromatin-directed proteomics

Towards transcription-coupled DNA repair in Xenopus egg extract

Poster presenter: Tycho Mevissen

A portrait of scientist Tycho Mevissen
Tycho Mevissen, Harvard Medical School, USA. PHOTO: Tycho Mevissen

This poster and abstract contain unpublished data and are not available at this moment.

Tycho Mevissen is a postdoctoral research fellow in Johannes Walter’s lab at Harvard Medical School. He had completed his PhD with David Komander at the MRC Laboratory of Molecular Biology in Cambridge, UK, where he used structural and biochemical tools to elucidate the intricate mechanisms of enzymes in the ubiquitin system, in particular deubiquitinases (DUBs).

His current research interests in the Walter lab revolve around molecular mechanisms at the intersection of DNA transcription, replication and repair.

In particular, he is interested in understanding how elongating RNA polymerase II deals with various types of obstacles – including different DNA lesions – during transcription elongation. To study this, he uses Xenopus egg extract, which is a powerful cell-free system that has been successfully used to recapitulate a wide range of cellular DNA repair pathways.


RBMX enables productive RNA processing of ultra long exons important for genome stability

A portrait picture of scientist Sara Luzzi
Sara Luzzi, Newcastle University, UK. PHOTO: Sara Luzzi

Poster presenter: Sara Luzzi

Authors: Sara Luzzi, Gerald Hysenaj, Chileleko Siachisumo, Kathleen Cheung, Matthew Gazzara, Katherine James, Caroline Dalgliesh, Mahsa Kheirollahi Chadegani, Ingrid Ehrmann, Graham R Smith, Simon J Cockell, Jennifer Munkley, Yoseph Barash, and David J Elliott.

The nuclear RNA binding protein RBMX has a direct role in genome repair and is required for expression of the tumour suppressor BRCA2. Here we report that RBMX controls RNA processing of key genes involved in genome maintenance in breast cancer cells.

Our data demonstrate that RBMX represses a premature polyadenylation site that would truncate BRCA2 protein, and is essential for full-length mRNA expression from other genes important for genome stability. These include ETAA1, which encodes for a key replication fork protein, where RBMX and its protein interaction partner Tra2Ăź efficiently suppress a weak splice site to enable ETAA1 protein expression.

More generally, we propose that RBMX facilitates correct inclusion of unusually long exons within mature mRNAs by repressing cryptic RNA processing. Our data provide new molecular insights explaining the role of RBMX in DNA repair and genome maintenance.

Poster RBMX enables productive RNA processing of ultra-long exons important for genome stability

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Looking back on a year of organising virtual events

Exactly one year ago, the Covid-19 pandemic hit Europe. All on-site events had to be cancelled and we had to rethink our entire program. Our Course and Conference Officers worked really hard to create a virtual equivalent of EMBL’s on-site training offering.  We successfully launched our first virtual conference and many more followed. 

The learning curve was steep and so was the stress level. But when the going gets tough, the tough get going. Two of our Conference Officers, Nathalie and Diah, share with us their experience from being in the eye of the storm, the lessons they have learned and some tips for organising a virtual meeting.

Conference Officers Nathalie and Diah
Conference Officers Nathalie (left) and Diah

How does organising a virtual event compare to organising an on-site event?

Diah: “It is a different world, but equally fun! Organising a virtual event is harder than people think and often more challenging. Not getting to see anyone in person and mastering all sorts of virtual platforms can be quite tough.”

Nathalie: “Some of the milestones we have are the same, for example: preparing the website, programme, opening registration, emails with participants and invited speakers, abstract review and selection… But a huge bulk of the work is totally different: instead of booking buses and ordering catering, we are setting up Zoom webinars and populating the virtual platform.

The massive change has been adapting to the new tasks we have to do and how we should do them consistently for all our events. In our team we have numerous working groups looking at areas of event organisation and creating guidelines, procedures and templates that will help us all. It really is a whole team effort!”

Read: Why do we charge fees for virtual events?

What kind of feedback do you get from participants, speakers and organisers?

Nathalie: “The feedback I have received from speakers and participants has been great: they are so happy we converted our event to virtual instead of cancelling/postponing it. Initially a few speakers were disappointed for the event to turn virtual but the same people commented afterwards that they were impressed with how well it went. What is wonderful is that it is still so beneficial for them in their continued research.”

Diah: “Very humbling! Many agree that onsite face-to-face events are somehow irreplaceable but at the same time they are amazed at the number of benefits virtual events offer too! They give you more flexibility: you don’t have to travel across the world. Also, some people feel more comfortable asking questions in the virtual format. ”

What is the most important lesson you have learned about organising virtual events?

Nathalie: “It’s been necessary for us to turn to virtual events but the lessons we have learned are that virtual events are effective, valuable and have many advantages! We’ve noticed that participants feel more comfortable asking questions during Q&A, that virtual talks have had a wonderful response, that virtual networking works well and you can meet different people from all over the world just at your desk!

On a bigger scale, virtual events mean less travel and a lower carbon footprint and they are more inclusive as they allow some people to participate who couldn’t have done so before. This is hugely important and is a very positive outcome of this difficult situation and it will have an impact on how events are organised in the future.”

What do you miss most about on-site events?

Diah: “The buzz when everyone arrives and the ATC is full of people is very exciting – after all the planning, everyone is there! And my favourite moment is the end of the conference: everyone is smiling and happy and you wave goodbye to the buses that leave EMBL. That sense of relief and accomplishment at the same time. I miss that!”

Nathalie: “Parties! One of the best things about the onsite events is meeting the speakers and participants you’ve been in touch with for months and when it comes to the conference party, it is really fun to see everyone let their hair down and enjoy themselves! And taking silly pictures at the Photobooth with people is something I loved and a really cute memento of the conference. That is a small thing I miss too!”

What in your opinion makes virtual events better than on-site events?

Nathalie: “The inclusiveness: more participants can take part as there is not the same financial barrier (travel, accommodation) and people can join from anywhere in the world.”

Diah: “Virtual events are resilient. There is no need to cancel an event because of the weather or a disaster. Participants can attend the event from anywhere!”

Conference Officer Diah wearing a face mask in an empty auditorium during a virtual event
Conference Officer Diah working a shift in an empty Auditorium

A common criticism is that networking doesn’t work well in the virtual world. What is your experience with virtual social events?

Nathalie: “I think it is great to see how Zoom breakout rooms allow people to mix in small groups or 1-to-1. Particularly the speed networking translates very well.”

Diah: “It’s my favorite part of the programme and I am amazed at how well it has been accepted and running so far. We have had live-streamed concerts and participants love it. At one conference some of the scientific organisers even stayed for the whole duration of the social session and wanted to continue mingling even after it had finished.”

Read our blog on virtual speednetworking.

Top tips to keep in mind while organising a virtual event?

Nathalie: “First of all – be open-minded. There are so many new technologies out there and different things you can try!

Have clear guidelines and templates: you use so many different apps and systems that saving time when setting things up can be a lifesaver!”

Diah: “I would also say: Test, test and test. Glitches are always likely to happen, so be prepared and stay calm.”

Read our blog for more tips on how to organise a virtual event

How do you see the future of EMBL Events?

Nathalie: “I hope we will embrace this new world of virtual events and have effective hybrid events in the future: allowing for face-to-face interaction for those who want to come on-site, but also giving the opportunity for those who prefer to join virtually and get the benefit of being part of the event without having to leave their home!”

Diah: “I think hybrid events will take a central place in the format of EMBL Events in the future. But whatever the format will be, we will keep improving and finding the best way to support the scientific community.”

Looking back in general, what are your thoughts?

Diah and Nathalie: “It has been very rewarding during the last year to see how we at EMBL have been able to adapt to the situation we have found ourselves in and been able to ensure that we can still provide a platform for scientific exchange. The aim of EICAT is to provide excellent training to scientists, and, despite the challenges, this is being achieved virtually for the first time! We are really proud of being able to provide opportunities for this exchange of knowledge and research.

Personally, this time has also been one of continuous learning for all of us on the team. We have developed our skills and experience in a number of ways and massively increased our knowledge of online platforms and tools! It has truly been a time of teamwork as we have adapted into the virtual event world and we are grateful to everyone involved: our marketing team, our Photolab technicians, designers and scientific organisers. It has been a challenging but very valuable learning experience!”

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