Yesterday we held the third webinar in our new series, this time focusing on plant development and chaired by Development Editor Yrjö Helariutta. Here you’ll find recordings of the talks and their live Q&A sessions moderated by Yrjö.
Marta Mendes (from Lucia Colombo’s lab at the University of Milan)
‘The RNA dependent DNA methylation pathway is required to restrict SPOROCYTELESS/NOZZLE expression to specify a single female germ cell precursor in Arabidopsis’
Marta’s paper is coming out soon in Development.
Krisztina Ötvös (from Eva Benková’s lab at IST Austria)
‘Modulation of root growth by nutrient-defined fine-tuning of polar auxin transport’
A postdoctoral position is available from January 2021 in the “Developmental Genetics” laboratory (http://gendev.ulb.ac.be/bellefroidlab/). Our lab studies cortical and sensory neurogenesis. To do this, we use mouse genetics and gain and loss-of-function experiments in Xenopus. We are interested in understanding how some transcription factors we have previously identified as key cell fate determinants in the developing cerebral cortex (Dmrt3 and Dmrt5) and in somatosensory ganglia (Prdm12) function in neuronal specification and to identify novel important regulators of neuronal diversification. The selected candidate will be in charge of testing the functional importance of one recently identified new putative regulator of neuronal diversification. To approach the function of this gene, he/she will use knock-out and conditional overexpressing transgenic mice as well as gain and loss of function experiments in the Xenopus model.
Location
The laboratory is located in the Biopark Charleroi Brussels South in the Institute of Biology and Molecular medicine (IBMM) of the University of Brussels. It is also part of the ULB Neuroscience Institute (UNI – http://uni.ulb.ac.be/groups/developmental-genetics/) that integrates and synergizes brain researchers of all neuroscience perspectives, from molecular and cellular neurobiology to systems / cognitive and clinical neurosciences.
Qualification and experience
We are looking for highly motivated candidates with a background in molecular and developmental neurobiology. Preference will be given to applicants with experience in mouse genetics and/or with the Xenopus model system. The position is opened for one year renewable up to 2 years, starting as January 2021. Fluency in English is mandatory. The ability to speak French is not required.
Application
Interested candidates should send a letter of motivation describing their past research experiences and full CV with the name and e-mail address of 2 references to Eric Bellefroid (ebellefr@ulb.ac.be)
Selected recent related publications:
1. Desiderio et al. (2019). Cell Reports 26, 3522-3536.
2. Desmaris et al. (2018). J. of Neurosci. 38, 9105-9121.
3. Young et al., (2017) PNAS, 114, E5599-E5607
4. De Clercq et al., (2016) Cerebral Cortex, 28, 493-509.
5. Thélie et al., (2015) Development 142, 3416-28.
With this strange and difficult year drawing to a close, I wanted to take the opportunity to update our community on how things have been going at Development through pandemic times. In March, the entire staff of The Company of Biologists decamped from the office and started home working. We’re incredibly lucky to have secure jobs that can be done efficiently from home, and while there have certainly been some challenges with adapting to remote working, things have gone surprisingly smoothly and we have (we hope!) continued to provide a high level of service to our authors and readers.
We have been monitoring our activities and workflows closely since COVID-19 hit, and I have to say that, if you looked just at these metrics, you would hardly know the extent of the disruption we’ve all experienced this year. As labs across the world shut down, we thought we might either see a flood of submissions as researchers had more time to write or – conversely – a significant fall as people had so many other challenges to deal with and/or were unable to finish key experiments. What actually happened was neither of these things: the rate of both initial submissions and revisions has essentially kept pace with previous years.
We thought we might receive more short ‘Report’ format articles as projects were written up earlier than they might have been otherwise, but this has not been the case. For the same reason, we wondered whether there might be a dip in the quality of papers submitted, but editorial rejection and overall acceptance rates have held steady. One thing we have seen is a slight shift in the geographic origin of papers submitted to us, with more papers from China-based authors and fewer from Europe. Whether this is a consequence of the pandemic or a more general trend, though, is hard to tell at this point – particularly given that submissions from China have been growing in recent years anyway.
Something we definitely expected was a slowdown in our decision speeds, especially in the early months. We knew that our editors and reviewers were facing the challenges of closing down their labs and/or making them COVID-safe, moving their teaching and mentoring online and – in many cases – taking on additional caring and home-schooling responsibilities. And we did find that some papers were significantly delayed through editorial assessment and peer review; for those authors that did experience such delays, we’re sorry. But, amazingly, our average turnaround times have remained the same this year as last. And even more impressively, more referees accepted our invitations to review papers, and more of them returned their reports on or before their deadline.
One issue that particularly concerned us was the potential disproportionate effect of the pandemic on women. Several reports earlier in the year suggested that submission rates from women were likely to decrease as they bore the brunt of childcare (see e.g. https://www.nature.com/articles/d41586-020-01294-9). So have we seen any evidence of this at Development? We don’t record author or reviewer gender in our submission system (though this is something we’re working on) so any analysis is necessarily imperfect. But by running names through the genderize.io app, we can get some idea of the gender demographics of our community (I’d note, though, that genderize.io is particularly bad at accurately assigning gender to non-Western names, and of course that this gender assignment is binary and therefore inherently limited). In 2018/2019, 31% of corresponding authors and 48% of first authors for whom gender could confidently be assigned were women. In 2020 (to the end of October), those numbers were 32% and 49%. What about referees? Again looking only at those individuals for whom we could confidently assign gender, 35% were women as compared to 32% in 2018/2019. Pre-pandemic, women were slightly less likely to accept an invitation to review than men, but this year, that trend has reversed. Overall, the data suggest an increasing representation of women among both our author and reviewer pool in recent years, and we hope this trend will continue.
The fact that the metrics for 2020 have looked so ‘normal’ does not mean that researchers have not found the year incredibly tough. Rather, it pays testament to the dedication and resolve of our community to keep going through these difficult times. And while 2021 brings the promise (fingers crossed!) of widely-accessible vaccines, the pandemic is not yet over, and the inevitable economic downturn will present its own financial challenges to the research sector. So I’d like to thank everyone who has contributed to and interacted with the journal this year, and who will do so in the year(s) to come – your support is hugely appreciated.
Unregulated cell proliferation can be disastrous for development and underlies the progression of cancers throughout the lifespan. A new paper in Development dissects the molecular regulation of a key cell proliferation promoter (and infamous oncogene) Myc, using Drosophila as a model system. We caught up with Olga Zaytseva, recent PhD graduate and one of the paper’s first authors, and her supervisor Leonie Quinn, Associate Professor at the John Curtin School of Medical Research in Canberra, to find out more.
Olga (L) and Leonie (R)
Leonie, can you give us your scientific biography and the questions your lab is trying to answer?
LQ After my PhD studies in Adelaide I conducted postdoctoral research at the Peter MacCallum Cancer Centre, investigating growth and cell cycle control. In 2007, I established my own group at the University of Melbourne, and later relocated to the John Curtin School of Medical Research in Canberra. My laboratory uses Drosophila to elucidate molecular mechanisms patterning cell and tissue growth during animal development. Our interest in RNA-binding proteins ‘moonlighting’ in transcriptional roles began over a decade ago when we demonstrated the splicing factor Hfp inhibits cell growth through transcriptional repression of the master regulator of growth, Myc. Subsequent studies revealed that a second splicing factor, Psi, also interacts with RNA Polymerase II machinery, in this case activating Myc transcription to promote cell and tissue growth. In our current paper, we report that the Argonaute family RNA binding protein, AGO1, functions outside of canonical functions in the miRNA-dependent RNA-induced silencing complex (RISC), repressing Myc transcription to inhibit cell and tissue growth.
And Olga – how did you come to work in Leonie’s lab and what drives your research today?
OZ During my undergraduate studies at Melbourne University on a path to a medical degree, I became particularly fascinated by studies of animal development, so I decided to seek out opportunities for research experience in this area. After seeing several beautiful images of the Drosophila wing on the Quinn lab website, I decided to approach Leonie and with her help I was lucky enough to receive a summer studentship to complete a short project on the roles of the transcription factor ASCIZ, previously uncharacterised in flies. I felt very inspired by Leonie’s passion, and this experience of the excitement and rewards of scientific enquiry motivated me to continue on to Honours and then a PhD degree under Leonie’s supervision. My PhD, which I have recently completed, gained insights into how the transcription regulator and single stranded DNA/RNA binding protein Psi acts to control growth and development. From the studies conducted in our lab, I am particularly interested in how transcription regulators such as Psi are able to control particular networks of genes in different cell and tissue types.
How has your research been affected by the COVID-19 pandemic?
OZ & LQ We feel quite fortunate in Australia, given the low number of cases and the stringent measures taken by the government to prevent the spread of infection and to widely test the population. The preventative lockdown measures meant that we’ve had limited access to the lab for several weeks, but given that many lives have been saved as a result of the restrictions, they are entirely warranted. Procedures are already underway to resume operations which means it’s not too long until our experiments can be gradually commenced again.
Let’s get to your current paper then – what was previously known about the link between Myc, Argonaute proteins and growth control?
OZ & LQ Although Myc is a well-established regulator of cell and tissue growth in both mammals and Drosophila, the links between AGO1 and Myc-driven growth have not been investigated. AGO1 proteins have been most thoroughly characterised as having roles in the RISC, where they are guided by the sequences of particular miRNAs/miRs to degrade target mRNAs. The regulation of Myc mRNA via RISC and miR-308 has been previously demonstrated by Julie Goodliffe’s group in Drosophila embryos; however, many miRs have tissue-specific targets and our work has shown that in the context of the wing, AGO1 does not control Myc via a RISC-dependent mechanism. Our study adds to the body of work that implicates Argonaute proteins in transcriptional control within the nucleus, for example via Polycomb Group transcriptional repressors.
AGO1 knockdown increases nucleolar size.
Can you give us the key results of the paper in a paragraph?
OZ & LQ We have discovered a previously unreported role for AGO1 as a repressor of Myc transcription and, as a result, growth of the Drosophila wing. We depleted AGO1 specifically in the developing wing, and observed strikingly increased ribosome biogenesis, nucleolar size and cell growth. AGO1 physically interacts with a key regulator of Myc transcription, Psi. AGO1 depletion increased Myc mRNA and protein levels, and the overgrowth seen after AGO1 knockdown was dependent on Psi and Myc. Given the roles of AGO1 within RISC, we tested whether Myc was increased via the most likely miR candidates; however we did not observe changes to Myc mRNA after manipulation of miRs. Instead, we saw that AGO1 depletion promotes the RNA Polymerase II transcription of Myc, and that AGO1 directly associates with the Myc promoter.
Do you have clues as to how, at a molecular level, AGO1 inhibits Myc transcription?
OZ & LQ We saw that overgrowth as a result of AGO1 knockdown was dependent on Psi; therefore a likely possibility is that the interaction between AGO1 and the Myc promoter might repress the activity of Psi. The mammalian orthologue of Psi, FUBP1, acts to remodel single-stranded DNA at the MYC promoter which enables maximal RNA Polymerase II transcription. However, links between human AGO1 and FUBP1 have not been studied and would be interesting to follow up in the future. We also saw overlap between AGO1 and Polycomb in the nucleus, and given that previous studies implicated Polycomb in the autorepression of the Myc gene in response to elevated Myc, Polycomb may play a role in AGO1-mediated Myc repression in certain contexts. Furthermore, AGO1 is an RNA-binding protein – the repression of the Myc promoter may occur by recruitment of non-coding RNAs that restrict transcription.
Too much Myc expression is associated with most human cancers – might AGO1 be a useful way to dampen this activity?
OZ & LQ While increased levels of Myc are clearly important for tumour progression, the links between AGO1 and cancer are not well established. Across different tumour types, AGO1 can be either overexpressed or contain loss-of-function mutations, suggesting either oncogenic or tumour suppressive roles depending on the context. The wing epithelium, where we observed tumour suppressive activity of AGO1, provides insights into progression of epithelial tissue cancers such as breast or prostate. A further understanding of how AGO1 is recruited to the Myc promoter would be required to develop strategies that stimulate AGO1 Myc-repressive activity. However, given the potent Myc activation as a result of AGO1 knockdown, harnessing the repressive roles of AGO1 to inhibit cancer growth is an exciting prospect.
When doing the research, did you have any particular result or eureka moment that has stuck with you?
OZ For me, it was seeing the overgrown cells after AGO1 depletion: that was the moment which started the enquiry into how it might occur. Once we began to characterise the phenotype, including elevated ribosomal RNA, ribosomal proteins and increased nucleolar size, we gained more clues that pointed towards a link with Myc. Given the crucial roles Myc plays in many cancers, it’s exciting that we discovered a mechanism which could contribute to cancer progression.
And what about the flipside: any moments of frustration or despair?
OZ When seeking to determine whether AGO1 interacts with chromatin in the Drosophila wing, we initially took a genome-wide approach. However, after making the constructs and performing the sequencing, we didn’t get any enrichment signal, which was quite disappointing. Therefore we looked at the Myc promoter specifically and were able to observe AGO1 binding. However, any clues as to AGO1 transcriptional targets more widely in the cell would have been highly informative, and it’s an experiment we’d like to perform in the future.
What next for you after this paper?
OZ I’m very interested in the protein that led us to AGO1, Psi. Both Psi and the mammalian orthologue FUBP1 appear to play versatile roles in binding RNA and single-stranded DNA at promoters. In fact, there are many examples of proteins that originally were thought to exclusively bind RNA but were subsequently found to associate with DNA as well. This highlights the dynamic nature of DNA, which often doesn’t get considered – the textbook ‘double helix’ is in fact just one of the conformations, while many other arrangements of the DNA strands play significant regulatory roles. Understanding how proteins such as Psi interact with such structures is important for a full picture of transcriptional control. As a first step, we are investigating genome-wide targets of Psi which led us to the discovery that Psi regulates multiple genes with roles in growth and developmental patterning.
There are many examples of proteins that originally were thought to exclusively bind RNA but were subsequently found to associate with DNA as well.
Where will this work take the Quinn lab?
LQ Based on this work we will continue to investigate the nuanced context-dependent control of transcription by single-stranded DNA/RNA-binding proteins, which is a key interest of our lab.
Finally, let’s move outside the lab – what do you like to do in your spare time in Canberra?
LQ I voraciously read non-fiction – history and politics of all flavours.
OZ I enjoy getting outdoors to explore the many parks and forests around Canberra.
Videos of the talks and Q&As can now be found here!
We’re happy to confirm the next in our Development presents… webinar series will be chaired by our Editor Yrjö Helariutta (Sainsbury Laboratory, University of Cambridge / Institute of Biotecnology, University of Helsinki) and features three talks on various aspects of plant development.
Wednesday 2 December 2020 – 10:00 GMT
Marta Mendes (from Lucia Colombo’s lab at the University of Milan)
‘The RNA dependent DNA methylation pathway is required to restrict SPOROCYTELESS/NOZZLE expression to specify a single female germ cell precursor in Arabidopsis’
Krisztina Ötvös (from Eva Benková’s lab at IST Austria)
‘Modulation of root growth by nutrient-defined fine-tuning of polar auxin transport’
Kenji Nagata (from Mitsutomo Abe’s lab at the University of Tokyo)
‘Ceramides mediate positional signals in Arabidopsis thaliana protoderm differentiation’
The webinar will be held in Remo, our browser-based conferencing platform – after the talks you’ll have the chance to meet the speakers and other participants at virtual conference tables. If you can’t make it on the day, talks will be available to watch for a couple of weeks after the event (look out for details on the Node).
For more information about what to expect in Remo, go to
We seek a motivated and organized individual to join the Lyons Lab (https://www.lyonslab.org/) at the Scripps Institution of Oceanography (https://scripps.ucsd.edu/) to serve as lab manger and research assistant. The individual will assist the lab in funded projects on molluscan neurodevelopment, developmental gene regulatory networks, and biomineralization. The successful candidate will be responsible for lab organization, inventories, safety protocols, and care of colonies of marine invertebrates. In addition, the individual will conduct lab research such as PCR/cloning, in situ hybridization, microinjection/electroporation, collection of embryonic samples for RNAseq/ATAC-seq/scRNAseq, and microscopy. Previous experience with the above techniques, particularly research with embryos of marine invertebrates, is preferred but not required. The successful candidate will have exceptional organizational and record-keeping skills and will serve as a collaborator with other lab members. The Lyons Lab is dedicated to building and maintaining a diverse and inclusive lab culture. The Scripps Institution of Oceanography, a department at U.C. San Diego, provides an exceptional learning and research environment within the large San Diego Metropolitan Area. The application closes December 9th, and the position will be filled as soon as possible.
Our laboratory at the Federal Institute of Technology (EPFL) in Lausanne, Switzerland is looking for a postdoc to work in the field of gene regulation during mammalian development, by using in vitro cultured, ES cells-derived gastruloids (pseudo-embryos) as a model system. Key-words: Transcriptional regulation, enhancers, CRISPR/cas9, mutant gastruloids, epigenetic profiling, 3D chromatin structure, single-cell RNA-seq phenotyping, DORA, open science, Hox genes (but not only). We look for an independent and respectful colleague, with a strong interest and curiosity for basic research and life in general. Fully funded position.
Disease Models & Mechanisms, published by The Company of Biologists, is seeking enthusiastic and motivated applicants for the role of Features & Reviews Editor. Joining an experienced and successful team, including Editor-in-Chief Liz Patton, this is an exciting opportunity to make a significant contribution to a growing Open Access journal in the fast-moving field of translational research.
This is a permanent, full-time position, and is based in The Company of Biologists’ attractive modern offices on the outskirts of Cambridge, UK. Owing to the pandemic, an initial period of remote working may be necessary. Please see the full job description for further details.
To apply, or for more information, contact recruitment@biologists.com. Applications should be made as soon as possible and by 21 December 2020. Applicants should be eligible to work in the UK.
There is a 4-year PhD position available at the Sars International Centre for Marine Molecular Biology (www.sars.no/) in the lab of Dr. Patrick Steinmetz.
The successful applicant will study how starvation-induced degrowth is controlled in the sea anemone Nematostella vectensis. The project may also involve studying key aspects of degrowth in the sea anemone Aiptasia pallida in a comparative context. State-of-the-art functional techniques (CRISPR mutants & knock-in lines, transgenesis), and a diverse range of approaches from developmental biology, genetics, physiology and genomics are available for functional and genomic studies in Nematostella.
Further details and how to apply: https://tinyurl.com/y3h5tv8r
IMBA is opening a search for a group leader. It is an absolutely great place to do 100% basic research. Full freedom, no questions asked. You can find all info here. The deadline is the 10th of January.
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There is a 4-year PhD position available at the Sars International Centre for Marine Molecular Biology (